# Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

Daniel S. Müller

► To cite this version:

Daniel S. Müller. Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review. Beilstein Journal of Organic Chemistry, 2026, 22, pp.1-63. 10.3762/bjoc.22.1. hal-05456198

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# Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

Daniel S. Müller

## Review

Open Access

Address:
Univ. Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes) – UMR 6226, 263 Avenue du Général Leclerc, F-35000 Rennes, France

Email:
Daniel S. Müller - daniel.muller@univ-rennes.fr

Keywords:
alkenyl chloride; chloroalkenes; chloro olefins; vinyl chlorides

Beilstein J. Org. Chem. **2026**, 22, 1–63.
https://doi.org/10.3762/bjoc.22.1

Received: 17 September 2025

Accepted: 10 December 2025

Published: 02 January 2026

Associate Editor: M. Desage-El Murr

<figure><img src="image_3.png" /></figure>

© 2026 Müller; licensee Beilstein-Institut.

License and terms: see end of document.

## Abstract

Alkenyl chlorides constitute a synthetically valuable yet historically underexplored class of organohalides. First prepared in 1868 by Charles Friedel – best known for the Friedel–Crafts reaction – via the reaction of ketones with phosphorus pentachloride, these compounds have steadily gained attention over the decades. In recent years, their distinct reactivity and potential in organic synthesis have been increasingly recognized. This review provides a comprehensive overview of the synthesis and application of alkenyl chlorides, with a focus on developments over the past four decades. By organizing this growing body of work, I aim to highlight key advances and help guide the design of new transformations involving this important and versatile functional group.

## Introduction

Alkenyl chlorides, while less extensively investigated than their brominated analogues, constitute a synthetically valuable class of organohalides with distinct reactivity. Among halogens, chloride is unique in its virtually limitless availability, derived from the global abundance of sodium chloride. In contrast, bromide and iodide sources are geographically restricted – bromide is predominantly extracted from the Dead Sea [1], while iodide is primarily sourced from caliche deposits in Chile [2]. This concentration of supply raises potential concerns regarding long-term availability and geopolitical vulnerability. Recent interest in alkenyl chlorides has been driven by their occurrence in bioactive natural products (Figure 1) [3-5], pharmaceu-

ticals (Figure 2) [6], and pesticides [7] (Figure 2). Throughout this review, the term “alkenyl chloride” refers broadly to chloroalkenes beyond vinyl chloride ($CH_2=CHCl$), the monomer used in polyvinyl chloride (PVC) production.

Before detailing the synthesis and applications of alkenyl chlorides, we wish to acknowledge previous reviews that have addressed this class of compounds in part or within broader contexts. Figure 3 offers a structured overview of prior reviews to facilitate orientation within the existing literature. The earliest comprehensive account is found in Jacobs’ 1949 Organic Reactions chapter, “The Synthesis of Acetylenes”
<figure><img src="image_4.png" /><figcaption>**Figure 1:** Representative alkenyl chloride motifs in natural products. References: Pinnaic acid [8], haterumalide [9], credneramide A [10], kimbeamide A [11], costatol [12], costatone A [12], pitinoic acid B [13], penasin B [14], halomon [15], biselide E [16], malyngamide Q [17], welwistatin [18], violacene [19], jamaicamide C [20], spongistatin 1 [21], kimbelactone A [11], neomangiocol A [22], laingolide B [23], pterulone [24], (+)-chlorophorboxazole A [21].</figcaption></figure>
<figure><img src="image_5.png" /><figcaption>**Figure 2:** Representative alkenyl chloride motifs in pharmaceuticals and pesticides. References: clomifene [25], ethchlorvynol [26], cefaclor [27], clethodim [28].</figcaption></figure>

[29] which discusses the preparation of alkenyl chlorides via ketone chlorination using PCl₅ (Figure 3A). The synthesis of β-chlorovinyl ketones was later reviewed by Poland and Benson in 1966 (Figure 3B) [30]. More recently, Morandi and co-workers summarized transition-metal-catalyzed additions of alkynes to acyl chlorides to access β-chlorovinyl ketones (2024) [31]. A review by Sharma and Singh covers comprehensively the synthesis and application of β-halovinyl aldehydes [32]. It should be noted that the synthesis of β-chloroalkenes substituted with an electron-withdrawing group in the α-position (e.g., aldehyde, ketone, sulfone, nitro) is beyond the scope of this review. In 2011, Guinchard and Roulland reviewed Pd-catalyzed cross-couplings of 1,1-dichloroalkenes and boron-chlorination reactions in the context of natural product synthesis (Figure 3C) [33]. Takai's contribution to the field, particularly via chromium-mediated olefinations, is covered in a Comprehensive Organic Synthesis chapter (Figure 3D) [34,35]. Carbochlorination and carbonylchlorination reactions were reviewed by Petrone, Ye, and Lautens in their Chemical Reviews article on transition-metal-catalyzed C–halogen bond formation (Figure 3E) [36]. Exchange reactions were reviewed by Evano and Nitelet in 2018 (Figure 3F) [37]. In 2020, Gandelman and co-workers provided an overview of decarboxylative chlorination reactions of carboxylic acids (Figure 3G) [38]. Hoveyda's 2023 review highlights stereocontrolled olefin metathesis with molybdenum catalysts to access trisubstituted alkenes including alkenyl chlorides (Figure 3H) [39]. Two recent reviews by Lu [40] and Nishiwaki [41] provide overviews of current developments in the hydrochlorination of alkynes, highlighting emerging catalytic strategies (Figure 3I). It should be noted that the review by Petrone and Lautens also covers some hydrochlorination chemistry. A concise three-page overview of alkenyl chloride synthesis appeared in 1995 in a book chapter “Comprehensive Organic Functional Group Transformations” by C. J. Urch [42]. Lastly, Cao and co-workers published a mini-review in 2013, written in Chinese, summarizing advances in the synthesis of vinyl chlorides [43].

As illustrated by the summary of existing reviews (Figure 3), the synthesis of alkenyl chlorides encompasses a wide range of mechanistically distinct strategies. An overview and classification of these transformations – excluding decarboxylative processes – is provided in Figure 4. Each class is discussed in detail in chapter 1. However, several transformations do not fit cleanly into the defined categories and are therefore discussed under miscellaneous reactions (chapter 1.11). For areas already covered by prior reviews, repetition has been avoided unless inclusion of key historical reports, overlooked publications, or representative examples was deemed necessary to highlight fundamental concepts.

Given the extensive literature on the synthesis of alkenyl halides – including iodides, bromides, and chlorides – this review is limited to studies that report at least two distinct examples of alkenyl chloride formation. The preparation of 1,1-dichloroalkenes has been comprehensively reviewed by Chelucci and will not be revisited here [44]. Conversely, 1,2-dichloroalkene synthesis lies beyond the scope of the present discussion. Regarding the use of color in graphical representations, structural highlighting was applied selectively, only when judged necessary in the clear identification of the transformation or mechanism depicted.

Chapter 2 highlights key applications of alkenyl chlorides. The discussion begins with reductive metalation, reactions with organolithium reagents, and eliminations to terminal alkynes – some of which are also exemplified in chapter 1. This is followed by palladium- and nickel-catalyzed cross-coupling reactions. The chapter concludes with a selection of miscellaneous transformations illustrating the broader synthetic utility of this class of compounds.

This review aims to provide a comprehensive overview of synthetic approaches to alkenyl chlorides and applications thereof. However, as the literature proved vast and ever-expanding, some reports may have escaped our attention and certain com-
<figure><img src="image_6.png" /><figcaption>B) Pohland and Benson (1966) [30], Morandi (2024) [31], Sharma and Singh (2025) [32]</figcaption></figure>

<figure><img src="image_7.png" /><figcaption>C) Guinchar and Roulland (2011) [33]</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>D) Takai (1986) [34]</figcaption></figure>

<figure><img src="image_9.png" /><figcaption>E) Petrone and Lautens (2016) [36]</figcaption></figure>

<figure><img src="image_10.png" /><figcaption>F) Evano and Nitelet (2018) [37]</figcaption></figure>

<figure><img src="image_11.png" /><figcaption>G) Gandelman (2021) [38]</figcaption></figure>

<figure><img src="image_12.png" /><figcaption>H) Hoveyda (2023) [39]</figcaption></figure>

<figure><img src="image_13.png" /><figcaption>I) Lu (2024) [40] and Nishiwaki (2024) [41]</figcaption></figure>

<figure><img src="image_14.png" /><figcaption>**Figure 3:** Graphical overview of previously published reviews addressing the synthesis of alkenyl chlorides.</figcaption></figure>
<figure><img src="image_15.png" /><figcaption>**Figure 4:** Classification of synthetic approaches to alkenyl chlorides.</figcaption></figure>

pound classes remain beyond the scope of this article. Still, with over 200 references, we hope to offer a representative and valuable perspective on the field.

# Review

## 1 Synthesis of alkenyl chlorides

### 1.1 Chlorodeoxygenations

**Transformations of ketones to alkenyl chlorides with phosphorous pentachloride (PCl5):** Friedel first reported the reaction of PCl5 with acetophenone (1) in 1868 (Scheme 1A) [45]. Treatment of the resulting intermediate 2 – then presumed to be a gem-dichloride – with aqueous KOH led to the formation of phenylacetylene (3). In 1875, Louis Henry extended this transformation to ketone 4 (Scheme 1B) [46]. Exposure to PCl5 gave a mixture of chlorinated intermediates described as 5 and 6, which, upon prolonged treatment with ethanolic KOH, underwent elimination to afford allene 7. Henry also observed that thermal treatment of the dichloro intermediate 5 yielded the corresponding alkenyl chloride 6. In 1913, Faworsky revisited this transformation in an effort to prepare tetramethylallene (7).

(Scheme 1C) [47]. However, several attempts to reproduce Henry's procedure were unsuccessful. Instead, Faworsky isolated the α-chlorinated ketone 8 as the major product. To our knowledge, the exact cause of this divergent chemoselectivity observed by Henry and Faworsky has never been discussed in the literature.

Numerous reports describe the formation of alkenyl chlorides via treatment of ketones with PCl5. Notably, the reaction conditions vary widely across the literature, with solvents ranging from neat conditions to cyclohexane, hexanes, toluene, benzene, carbon tetrachloride, dichloromethane, and diethyl ether. Reaction temperatures span from -10 °C to 100 °C. The first detailed investigation of this transformation was reported by Kagan and co-workers [48], who demonstrated that the reaction of acetophenone (1) with PCl5 in refluxing benzene affords a complex product mixture (Scheme 2).

A second, very detailed investigation of this reaction was presented by Jung and Kwon [49]. Focusing on the synthesis of
<figure><img src="image_16.png" /><figcaption>B) Henry (1875) [46]</figcaption></figure>

<figure><img src="image_17.png" /><figcaption>C) Faworsky (1913) [47]</figcaption></figure>

<figure><img src="image_18.png" /></figure>

**Scheme 1:** Early works by Friedel, Henry, and Favorsky.

<figure><img src="image_19.png" /></figure>

**Scheme 2:** Product distribution obtained by H NMR integration of crude compound as observed by Kagan and co-workers.

efavirenz (21), a potent HIV-1 non-nucleoside reverse transcriptase inhibitor, they aimed to improve the preparation of compound 19, whose yield had previously been limited to 22% following a similar route. They noticed that in situ-generated species such as POCI₃ or HCl triggered ring opening of dichloride 15 to produce a mixture of alkenyl chlorides Z- and E-16 (Scheme 3).

Treatment of the reaction mixture with base resulted in the formation of four distinct products (17, 18, 19 and 20) that proved challenging to separate. Screening of various bases revealed Hünig's base (iPr₂NEt) as uniquely effective in producing compounds 15 and 18 without contamination with E- or Z-16 isomers (Scheme 4). Additionally, it was found that several

aqueous work-up procedures induced ring opening of compounds 17 and 18. Ultimately, steam distillation directly from the reaction mixture afforded a toluene solution of compounds 15 and 18 in a combined yield of 44% (Scheme 4).

Additional optimization reactions showed that when the reaction was carried out at -10 °C even in the absence of Hünig's base dichloride 15 could be obtained in 92% yield. Treatment of 15 with KOt-Bu in toluene gave the desired compound 19 in 43% yield. The authors justified the low yield by the high volatility of 19 and loss thereof during work-up (Scheme 5).

It should be noted that the two-step procedure for converting a ketone into the corresponding alkyne can be accomplished in a
<figure><img src="image_20.png" /><figcaption>**Scheme 3:** Side reactions observed for the reaction of **14** with PCl₅.</figcaption></figure>

<figure><img src="image_21.png" /><figcaption>**Scheme 4:** Only compounds **15** and **18** were observed in the presence of Hünig's base.</figcaption></figure>

single step, as recently reported by Ghaffarzadeh and co-workers) [50]. They demonstrated that a 9:1 molar ratio of pyridine to PCl₅ converts ketones to alkynes within minutes under microwave irradiation (not shown).

High yields for alkenyl chlorides from ketones by reaction with PCl₅ were reported under various conditions on preparative scales. For instance, a patent from Vertex Pharmaceuticals describes the synthesis of alkenyl chloride **21** on a 360 and 580 mmol scale (Scheme 6A) [51]. The addition of a few drops of DMF was not commented. Surprisingly a significant decrease in yield was observed at the larger 580 mmol scale compared to the 360 mmol scale. Scott reported a high-yielding synthesis of **23** by heating diketone **22** with PCl₅ for several hours in toluene (Scheme 6B) [52]. Similarly, Jung obtained **25** in 69% yield after heating neat ketone and PCl₅ (Scheme 6C) [53]. The high yield of **25** is somewhat surprising, considering the

A) Vertex Pharmaceuticals (2016) [51]

<figure><img src="image_22.png" /></figure>

B) Scott (1997) [52]

<figure><img src="image_23.png" /></figure>

C) Jung (1982) [53]

<figure><img src="image_24.png" /><figcaption>**Scheme 6:** Various syntheses of alkenyl chlorides on larger scale.</figcaption></figure>

<figure><img src="image_25.png" /><figcaption>**Scheme 5:** Efficient synthesis of dichloride **15** at low temperatures.</figcaption></figure>
limited stability thereof. In our laboratory, **25** decomposed completely to a black tar within days, even when stored at –20 °C.

Several research groups reported the transformation of a broad range of ketones into the corresponding alkenyl chlorides with PCl₅ in boiling cyclohexanes (Scheme 7; product **26** [54], products **27**, **36**, and **37** [55] and products **28–35**, **38** and **39** [56]). The yields varied considerably depending on the substrate, leading to the following conclusions: (a) unhindered ketones lacking functional groups generally react in high yields; (b) sterically hindered ketones provide products **33**, **36**, and **39** with low yields; (c) electron-rich acetophenone derivatives, such as the *p*-methoxy-substituted example **34** afforded only low yields.

It is noteworthy that performing the synthesis of **26** under neat conditions with an excess of PCl₅ afforded substantial amounts of dichloride **41** (Scheme 8A) [57]. Engler showed that the use of a large excess of PCl₅ and prolonged reaction times can even favor the formation of trichloride **43** (Scheme 8B) [58].

Finally, it should be noted that, in contrast to five- and six-membered ring systems, Nagendrappa reported that medium-ring cycloalkanones afforded complex product mixtures, with the desired alkenyl chlorides isolated in purities below 85% (not shown) [59].

**Transformations of enols to alkenyl chlorides with phosphorous pentachloride (PCl₅):** β-Chlorovinyl ketones and esters represent highly versatile intermediates, as the chloride moiety is readily displaced by a wide range of nucleophiles (for example Scheme 9) [60]. These compounds are efficiently obtained in high yields from the corresponding ketones by treatment with PCl₅. Interestingly, an excess of PCl₅ does not lead to significant amounts of undesired side products. For excellent reviews concerning the synthesis of β-chlorovinyl ketones the reader is referred to Figure 3B and references mentioned therein.

**Other phosphorus-based procedures:** Heller reported the transformation of **48** to **49** using a mixture of PCl₅ and PCl₃

<figure><img src="image_26.png" /><figcaption>**Scheme 7:** Scope of the reaction of ketones with PCl₅ in boiling cyclohexane.</figcaption></figure>
A) Carroll (1951) [57]

<figure><img src="image_27.png" /></figure>

B) Engler (1989) [58]

<figure><img src="image_28.png" /><figcaption>**Scheme 8:** Side reactions occur when using excess amounts of PCl₅.</figcaption></figure>

<figure><img src="image_29.png" /><figcaption>**Scheme 9:** Formation of versatile β-chlorovinyl ketones.</figcaption></figure>

[61]. The authors did not comment on PCl₃ as additive. Both, the formation of the alkenyl chloride and the corresponding alkyne **50** by elimination with LDA were achieved in superb yields (Scheme 10).

Gross and Gloede introduced catechol–PCl₃ as an effective reagent for the conversion of ketones to the corresponding alkenyl chlorides [62] (Scheme 11A). Hudrlik later demonstrated that, in the case of 2-methylcyclohexanone (**54**), this reagent markedly alters the product distribution compared to PCl₅ [63] (Scheme 11B). However, since the reaction condi-

tions differ significantly, it remains unclear whether the product distribution is driven by the reagent itself or by the reaction conditions employed.

In 2007, Prati reported the use of (PhO)₃P–halogen-based reagents for the synthesis of alkenyl halides (Scheme 12) [64]. A variety of alkenyl chlorides was obtained in good yields, with functional groups such as esters and boronates well tolerated. When camphor was treated with (PhO)₃P·Cl₂ (TPPCl₂), the two constitutional isomeric chloro derivatives **66** and **67** were formed in a 65:35 ratio. In the case of non-enolizable ketones

<figure><img src="image_30.png" /><figcaption>**Scheme 10:** Mixture of PCl₅ and PCl₃ used for the synthesis of **49**.</figcaption></figure>
<figure><img src="image_31.png" /><figcaption>B) Hudrlik (1985) [63]</figcaption></figure>

<figure><img src="image_32.png" /><figcaption>**Scheme 11:** Catechol–PCl₃ reagents for the synthesis of alkenyl chlorides.</figcaption></figure>

<figure><img src="image_33.png" /></figure>

<figure><img src="image_34.png" /></figure>

9
87% yield

<figure><img src="image_35.png" /></figure>

58
78% yield
Z/E = 95:5

<figure><img src="image_36.png" /></figure>

59
86% yield

<figure><img src="image_37.png" /></figure>

60
76% yield

<figure><img src="image_38.png" /></figure>

61
91% yield

<figure><img src="image_39.png" /></figure>

62
96% GC yield

<figure><img src="image_40.png" /></figure>

63
94% GC yield
Z/E = 60:40

<figure><img src="image_41.png" /></figure>

64
96% GC yield

<figure><img src="image_42.png" /></figure>

65
80% yield

<figure><img src="image_43.png" /></figure>

56
81% yield
56/55 = 55:45

<figure><img src="image_44.png" /></figure>

66
82% yield
66/67 = 65:35

<figure><img src="image_45.png" /></figure>

68
93% yield

<caption>**Scheme 12:** (PhO)₃P–halogen-based reagents for the synthesis of alkenyl halides.</caption>
such as benzophenone, dichlorodiphenylmethane **68** was obtained in 93% yield. Aldehydes consistently afforded gem-dichlorides in excellent yields, regardless of enolizability (not shown). It is also worth noting that as early as 1959, Horner reported the synthesis of 1-chlorocyclohexene in 45% yield from cyclohexanone using PPh₃Cl₂ complex (not shown) [65].

In 2005, Kamei reported that alkenyl chlorides could be efficiently prepared from the corresponding alkenyl phosphate intermediates via treatment with a triphenylphosphine–chlorine complex (Scheme 13) [66].

A major disadvantage of the Prati, Horner and Kamei procedures is that the active phosphorous species has to be freshly prepared by bubbling highly toxic, elemental chlorine into solutions of P(OPh)₃ or PPh₃.

In 1993, Comins and co-workers reported the serendipitous discovery that N-acyl-2,3-dihydro-4-pyridinones react with the Vilsmeier reagent to afford the corresponding alkenyl chlorides (Scheme 14) [67]. Notably, dihydropyridones failed to react with POCl₃ in the absence of DMF.

In 2003, Wähälä reported a closely related reaction in which an in situ-generated Vilsmeier reagent converted aryl ketones bearing electron-donating substituents at the *ortho*- or *para*-position into alkenyl chlorides [68]. The reported yields corresponded to crude products and therefore do not reflect isolated yields of pure compounds (Scheme 15).

In 2006, Apotex reported the synthesis of alkenyl chlorides using POCl₃ in the presence of triethylamine and a copper catalyst (Scheme 16) [69]. The preparation of compound **84** is of

<figure><img src="image_46.png" /><figcaption>**Scheme 13:** Preparation of alkenyl chlorides from alkenyl phosphates.</figcaption></figure>

<figure><img src="image_47.png" /><figcaption>**Scheme 14:** Preparation of alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.</figcaption></figure>
<figure><img src="image_48.png" /><figcaption>**Scheme 15:** Preparation of electron-rich alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.</figcaption></figure>

<figure><img src="image_49.png" /></figure>

<figure><img src="image_50.png" /></figure>

<figure><img src="image_51.png" /></figure>

<figure><img src="image_52.png" /><figcaption>**Scheme 16:** Cu-promoted synthesis of alkenyl chlorides from ketones and POCl₃.</figcaption></figure>

industrial significance due to its application in the synthesis of terbinafine (86), an antifungal agent.

The reaction attracted our interest, prompting a more detailed investigation. Kinetic studies with acetophenone revealed

an induction period prior to reaction onset (Figure 5). Elevated temperatures shortened the initiation time, whereas lower temperatures extended it to several hours. Both temperature and reaction time significantly influenced the overall yield.
<figure><img src="image_53.png" /><figcaption>**Figure 5:** GC yield of **9** depending on time and reaction temperature.</figcaption></figure>

The decline in yield over time can potentially be attributed to polymerization side reactions of product **9** under the reaction conditions. Visual evidence of polymerization included difficulty in cleaning the reaction flask and the formation of solid polymer deposits that were irreversibly adhered (Figure 6, oval stirring bar left a mark in the solid polymer).

<figure><img src="image_54.png" /><figcaption>**Figure 6:** Broken reaction flask after attempts to clean the polymerized residue.</figcaption></figure>

Various catalyst loadings of CuCl (5–20 mol %) were evaluated, with 15–20 mol % required to achieve useful yields of **9** within several hours (Figure 7). Mechanistic analysis proved challenging, as the catalyst is generated in situ and likely

present only in trace amounts. All our attempts to accelerate the reaction through addition of various mono- and bidentate phosphorus ligands were unsuccessful.

A similar trend was observed with $NEt_3$, which afforded optimal yields at 20–30 mol % loading (not shown). Thus, the reaction is synthetically valuable but necessitates careful control of reagent quantities and reaction conditions for optimal yields.

Chemists from Alkaloida reported that 4-chromanones undergo transformation to the corresponding 4-halo-2H-chromenes upon treatment with $PCl_3$ (Scheme 17) [70]. The reaction appears limited to electron-rich chromanones, as evidenced by decreased yields upon removal of the electron-donating ether substituent (e.g., compound **90**). The authors further noted that the products require cold storage due to their sensitivity.

**Deoxychlorination with acyl chlorides:** The first synthesis of alkenyl chlorides from acyl chlorides was reported by Moughamir and Mestdagh in 1999 (Scheme 18A) [71]. They observed that strongly acidic solvents, including trifluoroacetic acid and methanesulfonic acid, provided the corresponding products in good yields with excellent stereoselectivity, exclusively yielding the Z-isomer. Nonan-2-one required activation with the stronger methanesulfonic acid and gave a 91:9 regioisomeric mixture of **91** to **92**. 1-Tetralone provided the corre-
<figure><img src="image_55.png" /><figcaption>**Figure 7:** GC yield of **9** depending on the amount of CuCl and time.</figcaption></figure>

<figure><img src="image_56.png" /><figcaption>**Scheme 17:** Treatment of 4-chromanones with PCl<sub>3</sub>.</figcaption></figure>

sponding product **61** in only 7% yield; the acid additive was not specified in this case. The authors were unable to efficiently separate **61** from side product **94**, which was likely formed via addition of acetyl chloride to **61** followed by conversion of the ketone to the alkenyl chloride. Regarding the mechanism (Scheme 18B), acid-catalyzed enolization of the ketone is proposed (enol I), followed by acetylation under the reaction conditions (acetate II). Subsequent addition of HCl to intermediate II generates chloride III, which undergoes elimination to yield the desired product IV.

Kodomari and co-workers serendipitously discovered a related reaction in which a large excess of acetyl chloride (8 equivalents) in the presence of ZnCl<sub>2</sub> supported on silica gel converted ketones into the corresponding alkenyl chlorides (Scheme 19) [72]. The scope appears to be limited to aromatic ketones furnishing non-terminal alkenyl chlorides.

Su and co-workers reported the synthesis of alkenyl chlorides using a multicomponent reagent system (Scheme 20A). In an effort to render the transformation more environmentally
<figure><img src="image_57.png" /><figcaption>**Scheme 18:** Synthesis of alkenyl chlorides from the reaction of ketones with acyl chlorides.</figcaption></figure>

<figure><img src="image_58.png" /><figcaption>**Scheme 19:** ZnCl₂-promoted alkenyl chloride synthesis.</figcaption></figure>
A)

$$
\underset{\text{BTC}}{\mathrm{R1}}^{\mathrm{R2}} + \underset{(0.4 \text{ equiv})}{\mathrm{Cl}_{3}\mathrm{C}-\mathrm{O}-\mathrm{O}-\mathrm{C}Cl}
$$

$$
\begin{array}{c}
\text{DMF (1 mol \%)} \\
\text{PhCOCl (5 mol \%)} \\
\text{Sc(OTf)₃ (2 mol \%)}
\end{array}
\xrightarrow{\text{EtOAc, reflux, 8-24 h}}
\begin{array}{c}
\mathrm{Cl}_{3}\mathrm{C}-\mathrm{O}-\mathrm{O}-\mathrm{C}Cl \\
\mathrm{R1}^{\mathrm{R2}}
\end{array}
$$

$$
\mathrm{R1}^{\mathrm{R2}}
$$

$$
\mathrm{Cl-Ph}
$$

**58**
91% yield

$$
\mathrm{Ph-Cl}
$$

**96**
90% yield

$$
\mathrm{Cl-Ph}
$$

**104**
85% yield

$$
\mathrm{Cl-Ph}
$$

**105**
76% yield

$$
\mathrm{OMe-Cl}
$$

**106**
65% yield

$$
\mathrm{Cl-Ph}
$$

**107**
64% yield

$$
\mathrm{Cl-Ph}
$$

**108**
82% yield

$$
\mathrm{Cl-Ph}
$$

**109**
80% yield

$$
\mathrm{Br-Ph}
$$

**110**
79% yield

$$
\mathrm{Cl-Ph}
$$

**61**
74% yield

$$
\mathrm{Cl-Ph}
$$

**9**
31% yield

$$
\mathrm{Ph-Cl}
$$

**26**
30% yield

$$
\mathrm{Cl-Ph}
$$

**111**
18% yield

$$
\mathrm{Cl-Ph}
$$

**112**
25% yield

B) unsuccessful examples

$$
\mathrm{Cl-Ph}
$$

113

$$
\mathrm{Cl-Ph}
$$

114

$$
\mathrm{Ph-Cl}
$$

115

$$
\mathrm{Cl-Ph}
$$

116

C) proposed reaction sequence

$$
\text{117} \quad \text{Ph-Ph} \xrightarrow{\text{Sc(OTf)}_3} \text{118} \quad \text{Ph-Cl} \xrightarrow{\text{DMF}} \text{119} \quad \text{Ph-Cl}
$$

96

118

119

$$
\mathrm{CO_2 + HCl} \quad \text{DMF} \quad \text{BTC}
$$

BTC

D) benzoic acid chloride as promotor of the reaction

$$
\mathrm{Ph-Ph}
$$

117

$$
\begin{array}{c}
\text{PhCOCl (2.2 equiv)} \\
\text{Sc(OTf)₃ (2 mol \%)}
\end{array}
\xrightarrow{\text{EtOAc, rt, 8 h}}
\begin{array}{c}
\mathrm{Cl-Ph} \\
\text{Ph}
\end{array}
$$

$$
\mathrm{Cl-Ph}
$$

**96**
95% yield

96

<caption>**Scheme 20:** Regeneration of acid chlorides by triphosgene.</caption>
benign, benzoyl chloride was replaced with triphosgene [73] [bis(trichloromethyl) carbonate, BTC], a putative “greener” surrogate [74]. Nevertheless, the high vapor pressure and associated safety concerns of BTC [75,76], represent a notable limitation. The substrate scope parallels that described by Kodomari (Scheme 19), though it includes one example of a terminal alkenyl chloride (compound 9), obtained in modest yield. Several ketone substrates proved unreactive, affording no or only trace amounts of the desired products (Scheme 20B). The authors proposed that BTC functions by regenerating benzoyl chloride in situ from benzoic acid, thereby allowing the use of benzoyl chloride in catalytic quantities (Scheme 20C). Under similar conditions – benzoyl chloride (2.2 equiv), room temperature, absence of DMF – the alkenyl chloride 96 was isolated in 95% yield (Scheme 20D). The transformation is mechanically and conceptually closely related to earlier findings reported by Moughamir and Mestdagh (see Scheme 18).

In 2015, Kartika and co-workers reported a metal and acid-free synthesis of alkenyl chlorides using triphosgene (BTC) (Scheme 21) [77]. In the presence of excess pyridine, BTC mediated the transformation of various ketones into the corresponding alkenyl chlorides, which were obtained in moderate isolated yields despite consistently high GC yields. The authors attributed this discrepancy to product degradation during purification on neutralized silica gel (1% $NEt_3$) or neutral alumina. However, this hypothesis was not experimentally verified, as no

control experiment involving the passage of a pure, non-volatile alkenyl chloride through the purification media was reported to assess compound loss or degradation at the purification step.

## 1.2 Exchange reactions

This chapter deals with exchange reactions, meaning that a given substituent on the alkene is formally exchanged for chlorine. The reactions are very different from each other in terms of mechanism and for a full discussion the review by Evano should be consulted [37].

In 2010, Buchwald and co-workers reported a palladium-catalyzed transformation of vinyl triflates to alkenyl chlorides (Scheme 22A) [78]. An improved variant of this methodology was published the following year (Scheme 22B) [79]. Independently, in 2009, Hayashi described a ruthenium-catalyzed conversion of alkenyl triflates to alkenyl chlorides (Scheme 22C) [80]. A subsequent study from the same group demonstrated that $[Cp*Ru(MeCN)_3]OTf$ could serve as an alternative catalyst, thereby avoiding the need for in situ reduction of $Ru(III)$ to $Ru(II)$ by organometallic reagents such as Grignards (not shown) [81]. More recently, a collaborative study between Bayer and researchers at the University of Strasbourg disclosed a ruthenium-catalyzed halide exchange of vinyl fluorosulfonates, which were prepared from ketones and sulfuryl fluoride ($SO_2F_2$) in the presence of DBU (1,8-diazabicyclo[9.9.1]non-7-ene [9].

<figure><img src="image_59.png" /></figure>

<figure><img src="image_60.png" /></figure>

<figure><img src="image_61.png" /></figure>

<figure><img src="image_62.png" /></figure>

<figure><img src="image_63.png" /></figure>

<figure><img src="image_64.png" /></figure>

<figure><img src="image_65.png" /></figure>

<figure><img src="image_66.png" /></figure>

<figure><img src="image_67.png" /></figure>

<figure><img src="image_68.png" /></figure>

<figure><img src="image_69.png" /></figure>

<figure><img src="image_70.png" /></figure>

<figure><img src="image_71.png" /><figcaption>**Scheme 21:** Alkenyl chlorides from ketones and triphosgene.</figcaption></figure>
<figure><img src="image_72.png" /></figure>

122

<figure><img src="image_73.png" /></figure>

Pd₂(dba)₃ (1.5–2.5 mol %)
t-Bu BrettPhos (3.8–6.3 mol %)
KCl (1.5 equiv), PEG3400
2-butanone (1.5 equiv)
iBu₃Al (1.5 equiv)
toluene, 100 °C

(2 examples)

<figure><img src="image_74.png" /></figure>

123

88% yield

<figure><img src="image_75.png" /></figure>

124

Pd₂(dba)₃ (1.5 mol %)
BrettPhos (4.5 mol %)
KCl (2.0 equiv)

KF (0.5 equiv)
1,4-dioxane (0.25 M)
130 °C, 16 h
(2 examples)

<figure><img src="image_76.png" /></figure>

39

95% yield

<figure><img src="image_77.png" /></figure>

125

Ru(acac)₃ (3 mol %)
n-BuMgCl (12 mol %)

LiCl (1.2 equiv)
THF, 60 °C, 3 h

(2 examples)

<figure><img src="image_78.png" /></figure>

126

98% yield

<figure><img src="image_79.png" /></figure>

[RuCp*(MeCN)₃PF₆ (2.5–5.0 mol %)
LiCl (1.5 equiv)

THF, 1–16 h, rt

<figure><img src="image_80.png" /></figure>

n-non

<figure><img src="image_81.png" /></figure>

<figure><img src="image_82.png" /></figure>

<figure><img src="image_83.png" /></figure>

127

61% yield

<figure><img src="image_84.png" /></figure>

128

67% yield

<figure><img src="image_85.png" /></figure>

129

76% yield

<figure><img src="image_86.png" /></figure>

130

26% yield

<figure><img src="image_87.png" /></figure>

65

78% yield

131

84% yield

126

37% yield

9

41% yield

<figure><img src="image_88.png" /></figure>

132

Ni(OAc)₂·4H₂O (5 mol %)

Zn (10 mol %), cod (10 mol %)
LiCl (1.5 equiv)

1:3 DMA/THF (0.25 M), 23 °C, 16 h

THF, 60 °C, 3 h
(19 examples)

<figure><img src="image_89.png" /></figure>

133

90% yield

<figure><img src="image_90.png" /></figure>

134

NiCl₂·glyme (10 mol %)
bpy (15 mol %)
TBACl (2.4 equiv)
NMP

(+)C/(-)Ni foam, rt
4 mA, 4F/mol

(3 examples from alkenyl triflates)
(4 examples from alkenyl bromides)

<figure><img src="image_91.png" /></figure>

65

92% yield

<caption>**Scheme 22:** Various substitution reactions.</caption>
cyclo[5.4.0]undec-7-ene) (Scheme 22D) [82]. Complementary to this, Reisman and co-workers reported a nickel-catalyzed conversion of vinyl triflates to alkenyl chlorides in 2019 (Scheme 22E) [83]. In 2024, Payard, Perrin, and Vantourout introduced an electrochemically driven nickel-catalyzed halide exchange, enabling the conversion of alkenyl bromides and triflates to the corresponding chlorides using tetrabutylammonium chloride (TBACl) as the chloride source (Scheme 22F) [84].

A fundamentally different approach was developed by Evano and co-workers [85,86], who reported a vinylic Finkelstein-type halide exchange reaction (Scheme 23). This strategy leverages the decreasing bond-dissociation energies across the halogen series – C–Cl ($D_{298}(C-Cl) = 395$ kJ mol⁻¹) and C–Br ($D_{298}(C-Br) = 318$ kJ mol⁻¹) bonds compared to the C–I bond

($D_{298}(C-I) = 253$ kJ mol⁻¹) to drive the substitution of iodide or bromide by chloride. In the presence of a copper catalyst and tetramethylammonium chloride (Me₄NCl) as the chloride source, alkenyl iodides and bromides were efficiently converted to the corresponding alkenyl chlorides. Importantly, the transformation proceeded with full retention of the double bond geometry. For a comprehensive discussion, the reader is referred to the Evano's full account [37].

### 1.3 Hydrochlorination

One of the most widely produced alkenyl chlorides is vinyl chloride. As of 2025, its global annual production exceeds 50 million tons, driven almost exclusively by its use as the monomer for polyvinyl chloride (PVC) [87]. The hydrochlorination of acetylene remains a key industrial process for vinyl

<figure><img src="image_92.png" /><figcaption>**Scheme 23:** Vinylic Finkelstein reactions reported by Evano and co-workers.</figcaption></figure>
chloride synthesis – particularly in China, where approximately 70% of the total production is based on this route. The reaction is typically catalyzed by carbon-supported mercuric chloride which is a major environmental concern [88].

Due to the extensive body of literature and the large number of patents related to the hydrochlorination of acetylene, this area represents a distinct and specialized field within hydrochlorination chemistry. As such, it is not covered in this review, and the reader is referred to the recent comprehensive accounts by Li [89] and Mitchenko [90] for further details.

Hydrochlorination of terminal alkynes frequently results in complex product mixtures due to the greater reactivity of the initially formed alkenyl chloride intermediate (e.g., **150**, Scheme 24) towards further protonation – often proceeding via more stabilized tertiary carbocation intermediates (for example: **153** is more stable compared to initially formed alkenyl cation **152**, Scheme 24) [91]. This protonation pathway commonly leads to the formation of gem-dichloride species **151**, which can subsequently undergo hydrolysis in the presence of trace water to furnish the corresponding ketone (see Scheme 27, formation of ketone **167**) [92].

Furthermore, Melloni were the first to demonstrate that highly hindered internal alkynes resist double HCl addition (Scheme 25) [93]. In cases where a quaternary substituent is present (compound **155**), the reaction proceeds with excellent yields.

A more recent study by Kropp on surface-mediated hydrochlorination reactions (Scheme 26) [94] also demonstrated that hydrochlorination of 1-heptyne yields a mixture of three products **156**, **157**, and **158**.

The target alkenyl chloride **156** was isolated only in trace amounts, alongside isomerized alkene **157** and dichloride **158**. Notably, only the sterically hindered *tert*-butyl-substituted alkyne afforded the desired product **155** in high yields, whereas hydrochlorination of 4-octyne proved inefficient to deliver compound **159**.

Thus, the hydrochlorination of terminal aliphatic alkynes serves as a valuable benchmark reaction to differentiate between purely ionic and transition-metal-catalyzed hydrochlorination processes which often show highly monoselective reactions [95]. Somewhat surprisingly, a recent study by Dai demon-

<figure><img src="image_93.png" /><figcaption>**Scheme 24:** Challenge of selective monohydrochlorination of alkynes.</figcaption></figure>

<figure><img src="image_94.png" /><figcaption>**Scheme 25:** Sterically encumbered internal alkynes furnish the hydrochlorination products in high yield.</figcaption></figure>
<figure><img src="image_95.png" /><figcaption>**Scheme 26:** Recent work by Kropp with HCl absorbed on alumina.</figcaption></figure>

strated that aromatic alkynes can undergo hydrochlorination with good selectivity for the mono-addition when a nitro-methane/acetic acid solvent mixture is employed (Scheme 27) [96].

In contrast, selective monohydrochlorination is commonly observed for alkynes bearing coordinating substituents such as acetylenic ethers [97,98], ynones [99], ynamides [98-102], acet-

ylenic selenides [103], thioalkynes [98,104], acetylenic nitriles [105], propargyl amines [106], propargylic amides [107], propargylic thioethers [106], propynoic acids [105], and propynoates [105,108] (Figure 8).

Over the past two decades, considerable efforts have been devoted to the selective monohydrochlorination of alkynes, particularly through the use of transition-metal catalysis. Compre-

<figure><img src="image_96.png" /><figcaption>**Scheme 27:** High selectivities for monohydrochlorination with nitromethane/acetic acid as solvent.</figcaption></figure>

<figure><img src="image_97.png" /><figcaption>**Figure 8:** Functionalized alkynes which typically afford the monohydrochlorinated products.</figcaption></figure>
hensive reviews by Lu [40] and Nishiwaki [41] have extensively
ly covered these advances.

We also want to briefly mention the work on chlorosulfonylation [109-111] (Scheme 28A) and chloropentafluorosulfanylation of alkynes (Scheme 28B) [112]. Chloroaminations of alkynes are well known and have been summarized in recent work by Renzi concerning the chloroamination of allenes. (Scheme 28C) [113]. A simplified mechanistic proposal is shown in Scheme 28D, involving initial generation of a nitrogen-centered radical **165**, which undergoes intramolecular addition to the pendant allene to form a vinyl radical intermediate **166**. Subsequent interception of **166** by an N-Cl bond furnishes alkenyl chloride **164**.

## 1.4 Reaction of alkenyl metals with chlorine electrophiles

A wide range of alkenylmetal species has been employed for
the synthesis of alkenyl chlorides via reaction with chlorine
electrophiles (Scheme 29). In a study from 1978, Zweifel
demonstrated that 1,1-silyl(aluminum)alkenyl intermediates

(e.g., **167**) undergo highly selective chlorination at the
aluminum-bound site using *N*-chlorosuccinimide (NCS)
(Scheme 29A) [114]. Decades later, Ramazanov expanded this
approach, showing that alkenylaluminums (e.g., **169**) derived
from carboalumination react efficiently with mesityl chloride
(MsCl) to furnish alkenyl chloride **170** (Scheme 29B) [115]. In
contrast, analogous hydroalumination products obtained from
hydroalumination of alkynes with DIBAL-H gave only trace
amounts of the desired chlorinated products (not shown).
Chlorodeboronation offers another powerful entry to alkenyl
chlorides (Scheme 29C–E). Masuda [116], Petasis [117], and
Molander [118] have independently demonstrated that organo-
boranes, alkenylboronic acids, and trifluoroborates undergo
CuCl₂–, NCS–, or trichloroisocyanuric acid (TCICA)-mediated
chlorination to furnish alkenyl chlorides. Earlier, Levy showed
that alkenylcopper reagents could be selectively converted to
chlorinated products with excellent stereochemical control
using NCS (Scheme 29F) [119]. Kigoshi reported the reaction
of alkenylsilane with NCS to afford compound **176** which
served as building block for the total synthesis of 15-*epi*-hateru-
malide NA (Scheme 29G) [120]. Interestingly, the transformat-

<figure><img src="image_98.png" /><figcaption>B) radical chloropentafluorosulfanylation of alkynes</figcaption></figure>

<figure><img src="image_99.png" /><figcaption>C) chloroamination of allenes</figcaption></figure>

<figure><img src="image_100.png" /><figcaption>D) proposed mechanism</figcaption></figure>

<figure><img src="image_101.png" /><figcaption>**Scheme 28:** Related chorosulfonylation and chloroamination reactions.</figcaption></figure>
<figure><img src="image_102.png" /><figcaption>B) Ramazonov (2013): Al → Cl [115]</figcaption></figure>

<figure><img src="image_103.png" /><figcaption>C) Masuda (1992): B → Cl [116]</figcaption></figure>

<figure><img src="image_104.png" /><figcaption>D) Petasis (1996): B → Cl [117]</figcaption></figure>

<figure><img src="image_105.png" /><figcaption>E) Molander (2011): B → Cl [118]</figcaption></figure>

<figure><img src="image_106.png" /><figcaption>F) Levy (1977): Cu → C [119]</figcaption></figure>

<figure><img src="image_107.png" /><figcaption>G) Kigoshi (2003): Si → Cl [120]</figcaption></figure>

<figure><img src="image_108.png" /><figcaption>H) Schwartz (1975): Zr → Cl [123]</figcaption></figure>

<figure><img src="image_109.png" /><figcaption>**Scheme 29:** Reaction of organometallic reagents with chlorine electrophiles.</figcaption></figure>
ion of alkenylsilanes to alkenyl chlorides was also utilized in the total synthesis of (S)-jamaicamide C and laingolide B (not shown) [121,122]. Schwartz's work on alkenylzirconium complexes revealed high-yielding, stereoretentive transformations under similar conditions (Scheme 29H) [123]. In a complementary study, Srebnik showed that bimetallic 1,1-alkenyl species bearing both boron and zirconium centers selectively undergo chlorination at the zirconium site, leaving the boron moiety untouched (not shown) [124].

## 1.5 Elimination reactions

The first elimination-based synthesis of alkenyl chlorides was reported by Biltz as early as 1897 (Scheme 30A) [125]. Decades later, Dolby demonstrated that a 70:30 *E/Z* mixture of

precursors could be selectively converted into the pure *E*-alkenyl chloride **135** by treatment with NaOH in DMSO (Scheme 30B) [126]. Related strategies involving the addition of chlorine to alkenylsilanes or alkenylboranes, followed by base-induced elimination, were developed by Miller [127,128] and Kabalka [129] (Scheme 30C and D). In these cases, elimination was effected by fluoride or alkoxide, resulting in the loss of the boryl or silyl moiety and formation of the desired alkenyl chloride.

Alexakis, Normant, and Fugier reported the synthesis of conjugated alkenyl chloride **183** by chlorination of *cis*-diol **181** and subsequent elimination of product **182** with KOH (Scheme 31) [130].

<figure><img src="image_110.png" /><figcaption>**Scheme 30:** Elimination reactions of dichlorides to furnish alkenyl chlorides.</figcaption></figure>

<figure><img src="image_111.png" /><figcaption>**Scheme 31:** Elimination reactions of allyl chloride **182** to furnish alkenyl chloride **183**.</figcaption></figure>
Schlosser reported that treatment of 1,2-dichloroalkanes with sodium or potassium hydroxide in dimethoxyethane effected selective elimination, furnishing the corresponding alkenyl chlorides in useful yields (Scheme 32) [131].

Furthermore, he demonstrated that the stereochemical outcome is strongly influenced by the choice of solvent (Scheme 33) [132].

An interesting elimination of a dichlorocyclopropane was reported by Banwell in the context of the synthesis of tetracyclic frameworks related to gibberellins (Scheme 34) [133]. The authors do not propose a mechanism for this reaction. A related reaction was recently reported by Greatrex and co-worker (not shown) [134].

Kim and co-workers reported a convenient α-chlorination of enones mediated by in situ oxidation of HCl with oxone (potassium peroxymonosulfate) to generate molecular chlorine (Scheme 35A) [135]. Electrophilic addition of chlorine across the enone double bond, followed by triethylamine-induced elimination, furnished the corresponding alkenyl chlorides (e.g., compound **193**) in good yields. A similar procedure, employing K₂S₂O₈ as the oxidant, was recently reported by Wang and Yu (Scheme 35B) [136]. In their approach, the enamine substrate neutralizes the generated HCl, therefore eliminating the need for an external base such as NEt₃.

Similar products can also be accessed via a tandem oxidation/halogenation reaction of allylic alcohols, as recently reported by Chisholm and co-workers (Scheme 36) [137]. Their approach

<figure><img src="image_112.png" /><figcaption>**Scheme 32:** Detailed studies by Schlosser on the elimination of dichloro compounds.</figcaption></figure>

<figure><img src="image_113.png" /><figcaption>**Scheme 33:** Stereoselective variation caused by change of solvent.</figcaption></figure>
<figure><img src="image_114.png" /><figcaption>**Scheme 34:** Elimination of gem-dichloride **189** to afford alkene **190**.</figcaption></figure>

A) Kim (2004) [135]

$$ \chemfig{*6(=-=-(-O-Ph)-=)} \xrightarrow{\text{aq HCl (2 M) (2.2 equiv)}} \chemfig{*6(=-=-(-2 KHSO_5·KHSO_4·K_2SO_4-=-=)} \xrightarrow{\text{OXONE® (1.2 equiv)}} \chemfig{*6(=-=-(-CH_2Cl_2, 2 h, rt)-=)} \quad \text{191} $$

$$ \chemfig{*6(=-=-(-O-Ph)-=)} \xrightarrow{\text{NEt}_3 \ (5.6 \ equiv)} \chemfig{*6(=-=-(-CH_2Cl_2, 12 h, rt-=-=)} \quad \text{192} $$

$$ \chemfig{*6(=-=-(-O-Ph)-=)} \xrightarrow{\text{77\% yield (over 2 steps)}} \text{Z/E = 63:37} \quad \text{193} $$

B) Xie and Wang (2024) [136]

$$ \chemfig{*6(=-=-(-O-NHR²)-=)} \xrightarrow{\text{LiCl (2.0 equiv)}} \chemfig{*6(=-=-(-K_2S_2O_8 (4.0 equiv))-=-=)} \xrightarrow{\text{toluene, 120 °C, 4 h (26 examples)}} \chemfig{*6(=-=-(-O-Ph)-=)} \quad \text{NHR²} \quad \text{194} $$

<caption>**Scheme 35:** Oxidation of enones to dichlorides and in situ elimination thereof.</caption>

A) oxidation/halogenation reaction

$$ \chemfig{*6(=-=-(-OH)-=)} \xrightarrow{\text{DMSO (3 equiv)}} \chemfig{*6(=-=-(-CH_2Cl_2, -78 °C to rt)-=)} \xrightarrow{\text{then NEt}_3} \text{195} $$

B) proposed mechanism

$$ \chemfig{*6(=-=-(-OH)-=)} \xrightarrow{\text{Moffatt-Swern}} \chemfig{*6(=-=-(-O-Ph)-=)} \xrightarrow{\text{Cl}^-} \chemfig{*6(=-=-(-Ar-Cl)-=)} \xrightarrow{\text{NEt}_3} \chemfig{*6(=-=-(-O-Ph)-=)} $$

<caption>**Scheme 36:** Oxidation of allylic alcohols to dichlorides and in situ elimination thereof.</caption>

involves oxidation of the allylic alcohol under Moffatt-Swern conditions, followed by halogenation of the resulting enone to generate a chloronium ion. Subsequent ring opening by chlo-

ride furnishes the corresponding dichloride, which eliminates HCl in the presence of triethylamine to afford the desired chloroenone in good yields.
A recent report by Xiao also mentions the synthesis of dichlorides and their subsequent elimination to furnish alkenyl chlorides **34** and **25** (Scheme 37). However, no experimental details for these transformations are provided in the supporting information [138].

Engman reported the synthesis of alkenyl chlorides in a regionulated way from terminal olefins by a sequence involving addition of PhSeCl, chlorination of the resulting selenides with SOCl₂, and treatment with base (Scheme 38; yields refer to the transformation of **B** → **C**) [139].

A reaction which includes a fluorine–chlorine exchange and subsequent elimination of HCl was reported by Shibata and co-workers (Scheme 39) [140]. In this reaction the AlEt₂Cl has a dual role of fluorine–chlorine exchange reagent and as a base.

Similar exchange reactions with AlCl₃ and 1,1,1-trifluoroalkanes were recently reported by McLeod and co-workers (not shown) [141].

## 1.6 Electrophilic additions to alkynes

Melloni was the first to report the addition of alkynes to in situ-generated tertiary aliphatic carbocations (Scheme 40A) [142]. Treatment of *tert*-butyl chloride (**215**) with alkyne **3** in the presence of ZnCl₂ furnished alkenyl chlorides **155** and **9**, along with considerable amounts of polymeric byproducts [93,143]. Compound **155** was obtained with excellent stereoselectivity (>98:2 *E*/*Z*). Importantly, a lower alkyne-to-chloride ratio resulted in diminished yields of **155**.

The authors proposed that the key intermediate is a linear vinyl cation with a planar geometry (**217**, Scheme 40B), wherein the empty p-orbital lies in the molecular plane. As such, nucleo-

<figure><img src="image_115.png" /><figcaption>**Scheme 37:** Chlorination of styrenes with SOCl₂ and elimination thereof.</figcaption></figure>

<figure><img src="image_116.png" /><figcaption>**Scheme 38:** Chlorination of styrenes with SOCl₂ and elimination thereof.</figcaption></figure>
<figure><img src="image_117.png" /><figcaption>**Scheme 39:** Fluorine–chlorine exchange followed by elimination.</figcaption></figure>

philic attack occurs within this plane, aligned with the axis of the vacant orbital. In the case depicted in Scheme 40B, the face syn to the hydrogen is significantly more accessible than the face syn to the bulky tert-butyl group, accounting for the high E-selectivity observed. In contrast, alkyl groups with reduced steric demand led to mixtures of E- and Z-isomers (Scheme 40C). Notably, in these less-selective cases, excess alkyne was required to achieve synthetically useful yields. For example, compound **221** was obtained in only 15% yield when phenylacetylene and benzyl chloride were employed in a 1:1 molar ratio.

Mayr and co-workers reported a closely related transformation building on the earlier work by Melloni (Scheme 41) [144]. The

final example in their study (compound **229**) illustrates that reactions involving aliphatic alkynes proceed with low efficiency and poor yields under these conditions. Notably, Mayr demonstrated that ZnCl₂·etherate exhibits superior catalytic activity compared to anhydrous ZnCl₂. Although counterintuitive from the standpoint of Lewis acidity, this enhanced reactivity was attributed to the significantly improved solubility of the etherate complex, which compensates for its diminished intrinsic Lewis acidity [145].

This transformation remained unexplored for nearly a decade until Kabalka demonstrated that the benzylic cation could be accessed directly from the corresponding alcohol via its conversion to the benzyloxyboron dichloride (Scheme 42) [146].
<figure><img src="image_118.png" /></figure>

<figure><img src="image_119.png" /></figure>

<figure><img src="image_120.png" /><figcaption>**Scheme 40:** Intercepting cations with alkynes and trapping of the alkenyl cation intermediate with chloride.</figcaption></figure>

Subsequently, Kabalka reported an improved variant of the reaction in which $TiCl_4$ was employed in place of $BCl_3$ (Scheme 43) [147]. Interestingly, this modification led to an improved $E/Z$ ratio compared to the values reported by Melloni (compare selectivity for compound **219** in Scheme 38 and Scheme 41). The enhanced selectivity is likely attributable to the increased steric demand of the $TiCl_5^-$ counterion, which may impose greater steric interactions during the critical chloride addition step [148]. The high reported yield of product **225** is unexpected. Examination of the corresponding $^1H NMR$ spectrum revealed unusually broad signals, suggesting the possible presence of oligomeric or polymeric material in the isolated sample.

Biswas reported that benzylic, allylic, and propargylic alcohols could be activated by the addition of 0.4 equivalents of iron(III) chloride (Scheme 44) [149]. Although 19 examples were disclosed, limited information is available regarding functional group tolerance beyond an *N*-tosylated substrate to synthesize **234**. Consistent with earlier observations, aliphatic alkynes performed poorly under these conditions (compound **225**). One year later, Wang described a similar protocol employing 0.33 equivalents of $FeCl_3$ with the principal difference being the use of 1,2-dibromoethane as solvent [150].

The reported substrate scope was comparatively narrow (not shown).

Simultaneously, Liu demonstrated that $FeCl_3·6H_2O$ could also serve as an effective Lewis acid when the reaction temperature was raised to 50 °C (Scheme 45) [151]. As in previous studies, aliphatic alkynes were found to be inefficient coupling partners under these conditions (compound **238**).

Sasaki observed that hydrated zinc dichloride enabled the formation of alkenyl chloride **242** upon reaction of silylated alkyne **241** with 1-adamantyl chloride (**240**) (Scheme 46A) [152]. Revisiting this transformation, we found that hydrated indium trichloride afforded superior results under otherwise comparable conditions (Scheme 46B) [153]. In addition, we demonstrated that free alcohols could be employed as precursors using stoichiometric amounts of $FeCl_3$ (Scheme 46C) [153]. In both cases, only tertiary aliphatic substrates were examined, generating non-stabilized carbocations. While the transformations proceeded cleanly, yields were generally low and the scope was restricted to non-functionalized arylalkynes.

A one-pot procedure for the in situ generation of benzylic cations from hydrocarbon precursors using DDQ, followed by
$$
\begin{array}{c}
\text{222} \\
(1 \text{ equiv}) \\
\quad + \quad
\begin{array}{c}
\mathrm{Ph} \\
\equiv \\
\mathrm{3}
\end{array}
\quad \xrightarrow[\mathrm{CH}_2\mathrm{Cl}_2, -20 \,^{\circ}\mathrm{C}]{\mathrm{ZnCl}_2\cdot\mathrm{Et}_2\mathrm{O} (20 \, \mathrm{mol} \, \%)}
\quad
\begin{array}{c}
\text{223} \\
92\% \text{ yield} \\
88:12 \text{ E/Z}
\end{array}
\end{array}
$$

$$
\begin{array}{c}
\text{224} \\
(1 \text{ equiv}) \\
\quad + \quad
\begin{array}{c}
\text{Ph} \\
\equiv \\
\text{3} \\
(5 \text{ equiv})
\end{array}
\quad \xrightarrow[\text{CH}_2\text{Cl}_2, 40 \,^{\circ}\text{C}, 6 \,\text{h}]{\text{ZnCl}_2 \ (10 \, \text{mol} \, \%)} \quad
\begin{array}{c}
\text{225} \\
62\% \text{ yield} \\
88:12 \text{ E/Z}
\end{array}
\end{array}
$$

$$
\begin{array}{c}
\text{222} \\
(1 \text{ equiv}) \\
\quad + \quad
\begin{array}{c}
\text{Me} \\
\equiv \\
\text{226} \\
(2.5 \text{ equiv})
\end{array}
\quad \xrightarrow[\text{CH}_2\text{Cl}_2, -70 \,^{\circ}\text{C}, 15 \,\text{h}]{\text{ZnCl}_2 \cdot \text{Et}_2\text{O} (22 \, \text{mol} \, \%)} \quad
\begin{array}{c}
\text{227} \\
\approx 90\% \text{ yield} \\
9:11 \text{ E/Z}
\end{array}
\end{array}
$$

$$
\begin{array}{c}
\text{222} \\
(1 \text{ equiv}) \\
\quad + \quad
\begin{array}{c}
\text{n-Bu} \\
\equiv \\
\text{228} \\
(3.1 \text{ equiv})
\end{array}
\quad \xrightarrow[\text{CH}_2\text{Cl}_2, \text{rt}, 15 \,\text{h}]{\text{ZnCl}_2 \cdot \text{Et}_2\text{O} (60 \, \text{mol} \, \%)} \quad
\begin{array}{c}
\text{229} \\
31\% \text{ yield} \\
50:50 \text{ E/Z}
\end{array}
\end{array}
$$

<caption>**Scheme 41:** Investigations by Mayr and co-workers.</caption>

$$
\begin{array}{c}
\text{230} \\
(1 \text{ equiv}) \\
\quad + \quad
\begin{array}{c}
\text{Ph} \\
\equiv \\
\text{3} \\
(1.2 \text{ equiv})
\end{array}
\quad \xrightarrow[\text{CH}_2\text{Cl}_2, \text{rt}, 10 \,\text{h}]{\substack{\text{1) n-BuLi (1.1 equiv)} \\ \text{2) BCl}_3 \text{ (1.1 equiv)} \\ \text{(3 examples)}}} \quad
\begin{array}{c}
\text{219} \\
84\% \text{ yield} \\
90:10 \text{ E/Z}
\end{array}
\end{array}
$$

<caption>**Scheme 42:** In situ activation of benzyl alcohol **230** with BCl₃.</caption>
<figure><img src="image_121.png" /><figcaption>**Scheme 43:** In situ activation of benzylic alcohols with TiCl₄.</figcaption></figure>

interception with alkynes, was reported by Shi and co-workers (Scheme 47) [154]. However, the authors did not clarify whether the corresponding benzyl chloride was formed in the absence of the alkyne trapping agent (trapping of cationic intermediate by chloride anion).

Generation of tertiary aliphatic cations and intramolecular trapping with alkenes or alkynes is well known in the context of polyene cyclizations [155]. Building on Johnson's earlier work (Scheme 48A) [156], Fañanás and Rodríguez developed an intramolecular cationic cyclization strategy to access cyclohexenyl chlorides via chloride trapping of alkenyl cation intermediates (Scheme 48B) [157]. Comparable yields were obtained when either alkene or alcohol precursors were employed,

consistent with the formation of a common cationic intermediate. The method proved limited to six-membered ring systems, with no successful extension to other ring sizes. The proposed mechanism involves initial generation of a tertiary or benzylic carbocation, followed by intramolecular cyclization with a pendant alkyne to furnish a vinyl cation intermediate. This species is postulated to be trapped by the solvent, potentially forming a transient chloronium ion (CH₂Cl⁺). Reaction of this electrophilic intermediate with the BF₄⁻ counterion would be expected to yield CH₂FCl and BF₃; however, the authors did not investigate or confirm the formation of these by-products.

In 2006, Cook reported a related cyclization initiated by the activation of allyl bromide using InCl₃ (Scheme 48C) [158]. Very
<figure><img src="image_122.png" /></figure>
<figure><img src="image_123.png" /><figcaption>**Scheme 45:** In situ activation of benzylic alcohols with $FeCl_3$.</figcaption></figure>

A) Sasaki (1980)

<figure><img src="image_124.png" /></figure>

**240**
(1.0 equiv)

<figure><img src="image_125.png" /></figure>

**241**
(1.1 equiv)

<figure><img src="image_126.png" /></figure>

**242**
62% yield

B) Müller (2025)

<figure><img src="image_127.png" /></figure>

**240**
(1.0 equiv)

<figure><img src="image_128.png" /></figure>

**241**
(1.0 equiv)

<figure><img src="image_129.png" /></figure>

**242**
73% yield

C) Müller (2025)

<figure><img src="image_130.png" /></figure>

**243**
(1.0 equiv)

<figure><img src="image_131.png" /></figure>

**3**
(1.0 equiv)

<figure><img src="image_132.png" /></figure>

**8**
52% yield

<caption>**Scheme 46:** In situ activation of aliphatic chlorides and alcohols with $ZnCl_2$, $InCl_3$, and $FeCl_3$.</caption>

likely the first step involves the generation of allyl cation **I** by activation of the allyl bromide with $InCl_3$. Subsequent trapping by the appended alkyne will form alkenyl cation **II**. Cation **II** then reacts with dichloromethane to yield the corresponding alkenyl chlorides. This observation suggests that, under the reaction conditions, $InCl_3Br^-$ exhibits lower nucleophilicity than dichloromethane. Increased dilution of the reaction with

$CH_2Cl_2$ enhances the selectivity for chloride-to-bromide transfer, as evidenced by the ratio of Cl:Br shifting from 1:2 at 10 M $CH_2Cl_2$ to 29:1 at 0.1 M $CH_2Cl_2$. This finding indicates that non-indium coordinated solvent acts as the active nucleophile. The potential formation of chlorobromomethane in this reaction was not explored. When R = Ph (compound **248**), the formation of only alkenyl bromide **249** was observed. Several
<figure><img src="image_133.png" /><figcaption>**Scheme 47:** In situ generation of benzylic cations and trapping thereof with alkynes.</figcaption></figure>

other instances of chloride abstraction from dichloromethane have been documented in the literature, particularly in reactions involving alkenyl cation intermediates [159-166].

In 2023, Li, Lou and You reported a closely related hydrochlorination-alkyne addition sequence with respect to Johnson, Fañanás, and Rodríguez works (Scheme 49) [167]. Acetyl chloride reacts with water to give HCl which then readily protokesolates trisubstituted alkene 250 [168,169]. Subsequent trapping of the tertiary aliphatic cation 251 by the adjacent alkyne furnishes the alkenyl cation intermediate 252. Addition of chlorine, likely from $FeCl_4^-$ but potentially also from dichloromethane, to the alkenyl cation occurs from the less-hindered side, resulting in the formation of alkenyl chloride 253 in high yield.

The Frontier group recently disclosed an alkynyl halo-(aza)-Prins cyclization strategy (Scheme 50) [170-172]. This transformation furnishes synthetically versatile cyclized products bearing pendant halide functionalities, which can serve as substrates for subsequent halo-Nazarov cyclizations. The sequential nature of this approach enables rapid construction of structurally complex motifs in a concise number of steps. A recent account by Frontier and Hernandez provides a comprehensive and mechanistically summary of halo-Nazarov electrocyclizations [173].

## 1.7 Coupling reactions

As already mentioned in the introduction, the coupling reaction of 1,1-dichloroalkenes was recently covered by Guinchard and Roulland [33]. Key publications in this area are highlighted as follows. To the best of our knowledge, Corriu was the first to utilize alkenyl chlorides in nickel-catalyzed coupling reactions with aryl Grignard reagents (Scheme 51A) [174]. Shortly thereafter, Kumada reported a more comprehensive study involving coupling reactions of vinyl chloride with aryl Grignard reagents (Scheme 51B) [175]. The first instances of monocoupling reactions of 1,2-dichloroethylenes were reported by Linstrumelle, who leveraged stoichiometric control (using 5 equivalents of 1,2-dichloroethylene) to achieve selective monocoupling reactions catalyzed by nickel with Grignard reagents (Scheme 51C) [176]. Building on Sonogashira's findings [177], Linstrumelle also documented the first monoselective coupling of 1,2-dichloroethylenes with alkynes using palladium catalysis (Scheme 51C). Organ and Negishi demonstrated that the use of one equivalent of (E)-1-iodo-2-chloroethylene enables selective Sonogashira reactions, yielding alkenyl chlorides in high yields (not shown) [178-180].

Matsuda and co-workers reported a rhodium-catalyzed coupling reaction of 1,2-*trans*-dichloroethene with arylboronic esters (Scheme 52) [181]. They discovered that a rhodium/1,4-bis(diphenylphosphino)butane (DPPB) complex, in combina-
A) Johnson (1972) [156]

<figure><img src="image_134.png" /></figure>

B) Fañanás and Rodríguez (2017) [157]

<figure><img src="image_135.png" /></figure>

C) Cook (2006) [158]

<figure><img src="image_136.png" /><figcaption>**Scheme 48:** Intramolecular trapping reactions affording alkenyl halides.</figcaption></figure>

tion with a large excess of 1,2-*trans*-dichloroethene, facilitated monoselective cross-coupling reactions.

In 1987, Minato, Suzuki, and Tamao reported the first monoselective coupling reactions for 1,1-dichloroalkenes (e.g., compound **273**, Scheme 53) [182].

However, as noted by Negishi, this procedure results in mixtures or exclusively dialkylation products when applied to alkyl-substituted 1,1-dichloro-1-alkenes. Negishi and co-worker reported an improved version of the procedure using one equivalent of *N*-methylimidazole (NMI) (Scheme 54A) [183]. However, the reaction still resulted in 3–25% yield of the dialkylated
<figure><img src="image_137.png" /><figcaption>**Scheme 49:** Intramolecular trapping reactions affording alkenyl chlorides.</figcaption></figure>

<figure><img src="image_138.png" /></figure>

<figure><img src="image_139.png" /></figure>

<figure><img src="image_140.png" /><figcaption>**Scheme 50:** Intramolecular trapping reactions of oxonium and iminium ions affording alkenyl chlorides.</figcaption></figure>

product. Consequently, the reaction conditions required adaptation for each substrate to maximize the yield of the monoalkylated product. In a parallel work, Barluenga demonstrated that the use of 4 equivalents of 1,1-dichloroethylene in combination with XPhos or JohnPhos ligands enabled monoselective cross-coupling with alkenyl- and arylboronic acids (Scheme 54B) [184].

Though mechanistically not related it is noteworthy that dichloronium salts couple efficiently with alkenyl chlorides (not shown) [185,186].

## 1.8 Alkenyl chloride synthesis via olefin metathesis

Johnson and co-workers investigated complex **287**, which forms as a product of an initial metathesis cycle in the cross-metathesis
A) Corriu (1972) [174]

<figure><img src="image_141.png" /></figure>

B) Kumada (1972) [175]

<figure><img src="image_142.png" /></figure>

C) Linstrumelle (1981) [176]

<figure><img src="image_143.png" /></figure>

<figure><img src="image_144.png" /></figure>

<figure><img src="image_145.png" /></figure>

<figure><img src="image_146.png" /><figcaption>**Scheme 51:** Palladium and nickel-catalyzed coupling reactions to afford alkenyl chlorides.</figcaption></figure>

sis (CM) with alkenyl chlorides (Scheme 55) [187,188]. The authors observed that complex **287** rapidly decomposes into catalytically inactive species **288** and **289** (Scheme 55). Consequently, metathesis with *trans*-chloroethylene presents a significant challenge.

Grela was the first to demonstrate that metathesis is indeed feasible using phosphine-free catalysts [189]. The formation of the desired alkenyl chloride product was favored by the utilization of a large excess (100 equivalents) of (*E*)-1,2-dichloroethylene in the presence of the Grela catalyst **290** [190].
<figure><img src="image_147.png" /><figcaption>**Scheme 52:** Rhodium-catalyzed couplings of 1,2-*trans*-dichloroethene with arylboronic esters.</figcaption></figure>

<figure><img src="image_148.png" /><figcaption>**Scheme 53:** First report on monoselective coupling reactions for 1,1-dichloroalkenes.</figcaption></figure>

Depending on the substrate, stereoselectivity and yields can vary significantly (Scheme 56).

A subsequent study by Johnson confirmed Grela's findings using the standard Grubbs–Hoveyda 2nd generation catalyst **297** (Scheme 57) [188].

Schrock and Hoveyda reported a stereoretentive cross-metathesis reaction using commercially available *trans*-1,2-dichloroethene (Scheme 58) [191]. High yields and selectivities were achieved for alkenes with sterically demanding groups and styrenes. However, linear alkenes were obtained with low stereoretention.

In contrast to (*E*)-dichloroethene, (*Z*)-dichloroethene exhibited high levels of stereoretentivity for aliphatic alkenes (Scheme 59) [192]. Reactions with styrenes were inefficient, regardless of their electronic attributes.

Further improvement of the reaction was achieved by fine-tuning the Mo-metathesis catalyst (Scheme 60A–C). Schrock and Hoveyda also demonstrated that adding small amounts of HB.pin helps remove residual water, significantly enhancing the reaction efficiency [193]. This technique can also be applied to hydroxy- or carboxylic acid-containing olefins by adding 1.1 equivalents of HB.pin to perform traceless protection of these functional groups, which are otherwise incompatible with molybdenum metathesis catalysts. The in situ-generated boronic ester is conveniently cleaved by silica gel (Scheme 60D).

As mentioned in the introduction, a comprehensive account of this work has been recently reported by Hoveyda [39].

## 1.9 Olefinations of ketones and aldehydes

In 1961, Wittig and Schlosser reported the first synthesis of alkenyl chlorides via the classical Wittig reaction (Scheme 61A) [194]. The Wittig reagent was prepared by reacting triphenyl-
A) Negishi (2006) [183]

<figure><img src="image_149.png" /></figure>

<figure><img src="image_150.png" /></figure>

<figure><img src="image_151.png" /></figure>

**91**
75% yield

<figure><img src="image_152.png" /></figure>

**274**
85% yield

<figure><img src="image_153.png" /></figure>

**275**
83% yield

<figure><img src="image_154.png" /></figure>

**276**
70% yield

<figure><img src="image_155.png" /></figure>

**277**
73% yield

<figure><img src="image_156.png" /></figure>

**278**
85% yield

<figure><img src="image_157.png" /></figure>

**279**
85% yield

<figure><img src="image_158.png" /></figure>

**280**
82% yield

<figure><img src="image_159.png" /></figure>

**281**
82% yield

<figure><img src="image_160.png" /></figure>

**282**
82% yield

<figure><img src="image_161.png" /></figure>

**283**
80% yield

<figure><img src="image_162.png" /></figure>

**284**
90% yield

B) Barluenga (2006) [184]

<figure><img src="image_163.png" /></figure>

**285**
(4 equiv)

Pd₂(dba)₃ (0.5 mol %)
XPhos or JohnPhos (2 mol %)

K₃PO₄ or CsF (2 equiv)
toluene or dioxane, 70–100 °C
(12 examples)

<figure><img src="image_164.png" /><figcaption>**Scheme 54:** Negishi's and Barluenga's contributions.</figcaption></figure>

<figure><img src="image_165.png" /></figure>

**286** (Grubbs II)

<figure><img src="image_166.png" /></figure>

**260**

<figure><img src="image_167.png" /></figure>

**135**

<figure><img src="image_168.png" /></figure>

**287**

<figure><img src="image_169.png" /></figure>

<figure><img src="image_170.png" /></figure>

**288**

<figure><img src="image_171.png" /></figure>

**289**

<caption>**Scheme 55:** First mechanistic investigation by Johnson and co-workers.</caption>
$$ \underset{\text{260 (100 equiv)}}{\mathrm{R}} + \underset{\substack{\text{cat 290 (5–15 mol %)} \\ 50 \,^{\circ}\mathrm{C}, 6–20 \,\mathrm{h}}}{\mathrm{Cl}_2\mathrm{Cl}} \rightarrow \underset{\substack{\text{290 (Grela catalyst)} \\ \mathrm{R} \equiv \mathrm{Cl}_2\mathrm{Cl}}}{\mathrm{R}} $$

<figure><img src="image_172.png" /><figcaption>290 (Grela catalyst)</figcaption></figure>

<figure><img src="image_173.png" /></figure>

**291**
87% yield
Z/E = 58:42

<figure><img src="image_174.png" /></figure>

**292**
76% yield
Z/E = 60:40

<figure><img src="image_175.png" /></figure>

**139**
91% yield
Z/E = 83:17

<figure><img src="image_176.png" /></figure>

**293**
85% yield
Z/E >98:2

<figure><img src="image_177.png" /></figure>

**294**
35% yield
Z/E >98:2

<figure><img src="image_178.png" /></figure>

**295**
32% yield
Z/E >98:2

<figure><img src="image_179.png" /></figure>

**296**
52% GC-yield
Z/E >72:28

<caption>**Scheme 56:** First successful cross-metathesis with choroalkene 260.</caption>

$$ \underset{\text{Z-260}}{\mathrm{R}} + \underset{\substack{\text{297 (15 mol %)} \\ \mathrm{Cl}_2\mathrm{Cl}}}{\mathrm{Cl}_2\mathrm{Cl}} \rightarrow \underset{\substack{\text{297 (Grubbs–Hoveyda II catalyst)} \\ \mathrm{R} \equiv \mathrm{Cl}_2\mathrm{Cl}}}{\mathrm{R}} $$

<figure><img src="image_180.png" /><figcaption>297 (Grubbs–Hoveyda II catalyst)</figcaption></figure>

<figure><img src="image_181.png" /></figure>

**178**
90% yield
Z/E = 60:40

<figure><img src="image_182.png" /></figure>

**144**
50% yield
Z/E = 50:50

<figure><img src="image_183.png" /></figure>

**293**
70% yield
Z/E = 81:19

<figure><img src="image_184.png" /></figure>

**298**
20% yield
Z/E >56:44

<caption>**Scheme 57:** Subsequent studies by Johnson.</caption>

phosphine with formaldehyde in the presence of HCl, followed by treating the resulting alcohol **341** with thionyl chloride (Scheme 61A). The phosphonium salt was deprotonated with *n*-BuLi, and the corresponding phosphonium ylide was reacted with benzophenone or benzaldehyde to obtain the corresponding alkenyl chlorides **344** and **135**. In 1978, Miyano reported an improved procedure that prepares the phosphonium salt in one step from chloroiodomethane and typically the products are obtained as mixtures of stereoisomers (Scheme 61B) [195]. Today, the phosphonium salt **342** is commercially available (CAS: 5293-84-5) and is frequently employed for the forma-

tion of alkenyl chlorides (e.g., Scheme 60C) [196]. It is noteworthy that a highly *cis*-selective variant, necessitating a sophisticated phosphonium salt, was reported by Schlosser in 1993 [197].

In 2006, Berthelette reported the Julia olefination of α-halomethylsulfones with aldehydes, which furnished alkenyl chlorides in good to excellent yields (Scheme 62A) [198]. The requisite α-halomethylsulfones were synthesized in two steps from commercially available reagents, achieving synthetically useful yields (Scheme 62B). Systematic optimization studies
$$
\underset{\text{R}^2 = \text{H, Ph}}{\text{R}^1\text{-Cl}^2} + \underset{(5-10 \text{ equiv})}{\text{Cl}\text{-}\text{C(CH}_3)_2\text{Cl}} \xrightarrow[\text{benzene, 22 °C, 15 min to 4 h}]{\text{299 (3-5 mol %)}} \text{R}^1\text{-Cl}
$$

299

<figure><img src="image_185.png" /></figure>

<figure><img src="image_186.png" /></figure>

300

80% yield
92:8 E/Z
R² = H

<figure><img src="image_187.png" /></figure>

135

65% yield
>98:2 E/Z
R² = H

<figure><img src="image_188.png" /></figure>

301

54% yield
>98:2 E/Z
R² = H

<figure><img src="image_189.png" /></figure>

302

60% yield
>98:2 E/Z
R² = H

<figure><img src="image_190.png" /></figure>

137

69% yield
>98:2 E/Z
R² = H

<figure><img src="image_191.png" /></figure>

138

75% yield
>98:2 E/Z
R² = H

<figure><img src="image_192.png" /></figure>

303

59% yield
>98:2 E/Z
R² = H

<figure><img src="image_193.png" /></figure>

304

61% yield
>98:2 E/Z
R² = H

<figure><img src="image_194.png" /></figure>

305

61% yield
>98:2 E/Z
R² = H

<figure><img src="image_195.png" /></figure>

306

62% yield
>98:2 E/Z
R² = H

<figure><img src="image_196.png" /></figure>

307

69% yield
>98:2 E/Z
R² = H

<figure><img src="image_197.png" /></figure>

308

85% yield
>98:2 E/Z
R² = H

<figure><img src="image_198.png" /></figure>

309

93% yield
>98:7 E/Z
R² = H

<figure><img src="image_199.png" /></figure>

310

93% yield
>74:26 E/Z
R² = H

<figure><img src="image_200.png" /></figure>

311

95% yield
>98:2 E/Z (both)
R² = Ph

<figure><img src="image_201.png" /></figure>

312

70% yield
>98:2 E/Z
R² = Ph

<figure><img src="image_202.png" /></figure>

313

95% yield
>98:2 E/Z
R² = Ph

<figure><img src="image_203.png" /></figure>

314

90% yield
>98:2 E/Z
R² = Ph

<caption>**Scheme 58:** Hoveyda and Schrock's work on stereoretentive cross-metathesis with molybdenum-based catalysts.</caption>

revealed that additives, such as magnesium bromide etherate or HMPA, had a pronounced impact on both reaction efficiency and stereoselectivity.

In 2005, Yan reported that the direct oxidative addition of chloroform to a Mg–TiCl₄ bimetallic system generates a nucleophilic chloromethylenetitanium species that transforms a
### A) cross-metathesis with terminal alkenes

<figure><img src="image_204.png" /></figure>

<figure><img src="image_205.png" /></figure>

<figure><img src="image_206.png" /></figure>

<figure><img src="image_207.png" /></figure>

<figure><img src="image_208.png" /></figure>

<figure><img src="image_209.png" /></figure>

<figure><img src="image_210.png" /></figure>

<figure><img src="image_211.png" /></figure>

<figure><img src="image_212.png" /></figure>

<figure><img src="image_213.png" /></figure>

<figure><img src="image_214.png" /></figure>

<figure><img src="image_215.png" /></figure>

<figure><img src="image_216.png" /></figure>

<figure><img src="image_217.png" /></figure>

<figure><img src="image_218.png" /></figure>

### B) cross-metathesis with internal alkene **328**

<figure><img src="image_219.png" /></figure>

<figure><img src="image_220.png" /><figcaption>**Scheme 59:** Related work with (Z)-dichloroethene.</figcaption></figure>

ketone into the corresponding alkenyl chlorides (Scheme 63) [199].

## 1.10 Allylic substitutions

Allylic substitution of readily accessible alkenyl chlorides bearing a suitable leaving group at the allylic position enables effi-

cient introduction of the alkenyl chloride motif. Scheme 64 depicts representative examples by Boger [200], Taber [201], and Morken [202].

In 2012, Feringa and co-workers reported the first enantioselective allylic substitution of allylic gem-dichlorides with alkyl
<figure><img src="image_221.png" /><figcaption>A)</figcaption></figure>

<figure><img src="image_222.png" /></figure>

<figure><img src="image_223.png" /><figcaption>B)</figcaption></figure>

<figure><img src="image_224.png" /></figure>

<figure><img src="image_225.png" /></figure>

<figure><img src="image_226.png" /><figcaption>C)</figcaption></figure>

<figure><img src="image_227.png" /></figure>

<figure><img src="image_228.png" /></figure>

<figure><img src="image_229.png" /><figcaption>D)</figcaption></figure>

<figure><img src="image_230.png" /><figcaption>**Scheme 60:** Further ligand refinement and traceless protection of functional groups with HBpin.</figcaption></figure>

Grignard reagents (Scheme 65A) [203]. The reaction, catalyzed by a chiral copper complex generated in situ from CuTC and phosphoramidite ligand **361**, furnished the corresponding enantioenriched alkenyl chlorides in high yield and with exclusive formation of the Z-isomer. A decade later, Fañanás-Mastral and co-workers demonstrated that alkenylcopper species, gener-

ated via borocupration of terminal alkynes, underwent allylic substitutions to furnish Bpin-substituted alkenyl chlorides in high enantioselectivity (Scheme 65B) [204]. Key to the transformation was the use of a sulfonate-substituted N-heterocyclic carbene ligand, introduced as its imidazolium salt precursor **372**. More recently, the same group extended this methodology
### A) Wittig, Schlosser (1961) [194]

<figure><img src="image_231.png" /></figure>

<figure><img src="image_232.png" /></figure>

67% yield

<figure><img src="image_233.png" /></figure>

E/Z mixture

67% yield

### B) Miyano (1978) [195]

<figure><img src="image_234.png" /></figure>

<figure><img src="image_235.png" /></figure>

E/Z = 46:54

81% yield

### C) Honda (2012) [196]

<figure><img src="image_236.png" /><figcaption>**Scheme 61:** Alkenyl chloride synthesis by Wittig reaction.</figcaption></figure>

#### A) Julia-type olefination

<figure><img src="image_237.png" /></figure>

<figure><img src="image_238.png" /></figure>

#### B) synthesis of α-halomethyl sulfone

<figure><img src="image_239.png" /></figure>

72% yield (2 steps)

<caption>**Scheme 62:** Alkenyl chloride synthesis by Julia olefination.</caption>
<figure><img src="image_240.png" /><figcaption>**Scheme 63:** Alkenyl chloride synthesis by reaction of ketones with Mg/TiCl₄ mixture.</figcaption></figure>

to the use of acetylene as a highly useful C₂-building block, further broadening the synthetic utility of this approach (Scheme 65C) [205].

It is worth noting that allylic substitution of allylic gem-dichlorides has recently been exploited in the preparation of peptidomimetics incorporating chloroalkene dipeptide isosteres [206].

## 1.11 Miscellaneous reactions

In 2014, Du and Zhao reported that PhICl₂ in wet DMF was found transform alkenes regioselectively into the corresponding chloroformyloxylated products or α-chlorinated olefinic

products, depending on the type of structure of the original unsaturated starting material (Scheme 66) [207].

Similar products were obtained by Dauzonne and co-workers through the reaction of aldehydes with bromonitromethane in the presence of dimethylammonium chloride (not shown) [208]. Bonne and Rodriguez subsequently reported a slightly modified procedure in 2017 (Scheme 67) [209].

In 2008, Charette reported that treatment of benzyl bromides with “NaICHCl” furnished the corresponding styrenyl chlorides in good yields and with high E-selectivity (Scheme 68) [210].

Pace and co-workers recently reported an alternative strategy for alkenyl chloride synthesis employing lithium chloromethyl-enecarbenoids generated in situ from chloroiodomethane and MeLi (Scheme 69) [211]. Nucleophilic addition of the carbenoid to ketones furnishes lithium alkoxides, which, upon treatment with SOCl₂, undergo elimination to deliver alkenyl chlorides under mild basic conditions.

Chu and co-workers developed a dual photoredox/nickel catalytic system enabling the site- and stereoselective synthesis of

<figure><img src="image_241.png" /><figcaption>**Scheme 64:** Frequently used allylic substitution reactions which lead to alkenyl chlorides.</figcaption></figure>
A) Feringa (2012) [203]

<figure><img src="image_242.png" /></figure>

<figure><img src="image_243.png" /></figure>

361

<figure><img src="image_244.png" /></figure>

**362**
56% yield
95:5 er

<figure><img src="image_245.png" /></figure>

**363**
74% yield
99:1 er

<figure><img src="image_246.png" /></figure>

**364**
77% yield
97:3 er

<figure><img src="image_247.png" /></figure>

**365**
72% yield
98:2 er

<figure><img src="image_248.png" /></figure>

**366**
74% yield
90:10 er

<figure><img src="image_249.png" /></figure>

**367**
75% yield
95:5 er

<figure><img src="image_250.png" /></figure>

**368**
78% yield
98:2 er

<figure><img src="image_251.png" /></figure>

**369**
74% yield
90:10 er

<figure><img src="image_252.png" /></figure>

**370**
72% yield
97:3 er

<figure><img src="image_253.png" /></figure>

**371**
67% yield
98:2 er

B) Fañanás-Mastral (2022) [204]

<figure><img src="image_254.png" /></figure>

<figure><img src="image_255.png" /></figure>

372

C) Fañanás-Mastral (2024) [205]

<figure><img src="image_256.png" /></figure>

<figure><img src="image_257.png" /></figure>

373

<caption>**Scheme 65:** Enantioselective allylic substitutions.</caption>
<figure><img src="image_258.png" /></figure>

<figure><img src="image_259.png" /></figure>

<figure><img src="image_260.png" /><figcaption>**Scheme 66:** Synthesis of alkenyl chlorides bearing an electron-withdrawing group.</figcaption></figure>

<figure><img src="image_261.png" /><figcaption>**Scheme 67:** Synthesis of α-nitroalkenyl chlorides from aldehydes.</figcaption></figure>

γ-functionalized alkenyl chlorides from unactivated internal alkynes and various organochlorides (Scheme 70) [212].

In 2009, Lam and co-worker reported that bis-activated cyclopropenes undergo highly stereoselective ring-opening in the presence of stoichiometric magnesium halides to furnish multi-substituted alkenyl halides (Scheme 71) [213]. The transformation proceeds with excellent control of stereochemistry.

In 2017, Wang and co-workers reported the electrophilic chlorination of alkenyl MIDA boronates as a stereoselective route to

Z- or E-alkenyl chlorides [214]. Treatment with PhSeCl led predominantly to (Z)-chloroalkenes (Scheme 72A), while exposure to t-BuOCl furnished the corresponding E-isomers (Scheme 72B). Distinct mechanistic pathways were proposed for each transformation, supported by experimental studies.

Zweifel and Brown reported the synthesis of alkenyl chlorides via hydroalumination or hydroboration of chloroalkynes [215,216]. However, these methods are less practical relative to the direct reaction of alkenylmetal species with chlorine electrophiles (Scheme 73).
<figure><img src="image_262.png" /><figcaption>**Scheme 68:** Synthesis of alkenyl chlorides via elimination of an in situ generated geminal dihalide.</figcaption></figure>

<figure><img src="image_263.png" /></figure>

B) selected examples:

<figure><img src="image_264.png" /><figcaption>**Scheme 69:** Carbenoid approach reported by Pace.</figcaption></figure>

Durandetti and Maddaluno reported that intramolecular carbolithiation of chloro-substituted alkynes provides access to exocyclic alkenyl chlorides upon aqueous work-up (Scheme 74) [217]. However, isolation is challenged by significant isomerization. Although crude yields are consistently high, exposure to silica gel induces isomerization of the exocyclic double bond to the corresponding internal isomer, resulting in substantially diminished isolated yields.

In the context of their total synthesis of chertelline C, Herzon and co-workers investigated a series of chlorination conditions (not shown). Among these efforts, a highly selective radical chlorination of an enamide was developed (Scheme 75), enabling site-specific chlorination under mild conditions [218].

## 2 Applications of alkenyl chlorides

### 2.1 Eliminations

Chloroalkenes, regularly serve for the introduction of terminal alkynes. Several reactions were already shown in this review (Schemes 1, 5, 10, and 16). A recent example by Fañanás-Mastral and Müller is shown in Scheme 76 [153,205].

### 2.2 Reductive metalations

Few protocols were reported for the transformation of alkenyl chlorides into the corresponding lithium, sodium, and magnesium reagents (Scheme 77). Conia reported the lithiation of alkenyl chloride **26** (Scheme 77A) [219]. An organic synthesis procedure for the synthesis of (*E*)-1-propenyllithium from (*E*)-1-chloropropene was reported by Linstrumelle and Whiteside in
<figure><img src="image_265.png" /></figure>

<figure><img src="image_266.png" /></figure>

<figure><img src="image_267.png" /></figure>

<figure><img src="image_268.png" /></figure>

**399**
44% yield
94:6 Z/E

<figure><img src="image_269.png" /></figure>

**400**
60% yield
90:10 Z/E

<figure><img src="image_270.png" /></figure>

**401**
38% yield
91:9 Z/E

<figure><img src="image_271.png" /></figure>

**402**
44% yield
94:6 Z/E

<figure><img src="image_272.png" /><figcaption>**Scheme 71:** Ring opening of cyclopropenes in the presence of MgCl₂.</figcaption></figure>

1976 (not shown) [220]. Flaming reported the synthesis of an alkenyl sodium reagent from alkenyl chloride **431** (Scheme 77B) [221]. A detailed procedure of this transformation was subsequently reported by Nagendrappa [59]. Transformation of the sensitive alkenyl chloride (see Scheme 6C and discussion) into the corresponding Grignard reagent worked surprisingly well as demonstrated by Jung and co-workers (Scheme 77C) [53].

## 2.3 Reaction of alkenyl chlorides with organolithium reagents

In 1941, Wittig and Witt reported that β-chlorostyrene (**135**) undergoes rapid elimination upon treatment with phenyl- or *n*-butyllithium, affording the corresponding lithium phenyl-acetylide **434** (Scheme 78A) [222]. In 1967, Schlosser conducted a detailed mechanistic study of this transformation

(Scheme 78B). Kinetic analysis and isotope effect experiments with deuterated substrates revealed a stepwise pathway: initial deprotonation occurs at the α-position relative to the chlorine, followed by deprotonation at the β-position by a second equivalent of organolithium reagent to furnish lithium acetylide **434** [223,224]. In 1995, Linstrumelle reported a related work on chloroenynes (Scheme 78C) [225], which can be deprotonated at –100 °C with *n*-BuLi to generate the corresponding alkenyllithium reagents. These reagents react with various electrophiles, such as ethyl chloroformate, in good yields. Notably, metalation reactions with non-conjugated chloroalkenes or the corresponding (Z)-chloroenynes proved inefficient.

In 1964, Köbrich reported that treatment of alkenyl chlorides with *n*-butyllithium results in selective deprotonation at the position α to the chlorine (Scheme 79A) [226]. At low
<figure><img src="image_273.png" /><figcaption>**Scheme 72:** Electrophilic chlorination of alkenyl MIDA boronates to Z- or E-alkenyl chlorides.</figcaption></figure>

<figure><img src="image_274.png" /><figcaption>**Scheme 73:** Hydroalumination and hydroboration of alkynyl chlorides.</figcaption></figure>

temperatures, the resulting intermediate can be intercepted by electrophiles such as CO₂, affording the corresponding carboxylic acids upon aqueous work-up. At elevated temperatures, the major product observed is the corresponding

alkyne. The formation of this product is attributed to elimination of chloride, proposed to proceed via aryl-assisted 1,2-migration and concurrent expulsion of lithium chloride (Scheme 79B).
<figure><img src="image_275.png" /></figure>

**412**
83% yield
(n-BuLi)

**413**
92% yield
(PhLi)

**414**
35% yield
(n-BuLi)

**415**
54% yield
(PhLi)

**416**
55% yield
(PhLi)

<figure><img src="image_276.png" /></figure>

**417**
59% yield
(PhLi)

**418**
48% yield
(PhLi)

**419**
54% yield
(n-BuLi)

<figure><img src="image_277.png" /><figcaption>**Scheme 75:** Chlorination of enamine 420.</figcaption></figure>

In 1975, Cunico reported the reaction of alkenyl chlorides with alkyl- and aryllithium reagents (Scheme 80A) [227]. Treatment of α-chlorostyrene (9) resulted in addition-elimination products. The authors proposed that the nucleophilic addition of the organolithium reagent to the alkenyl chloride generates a lithi-

umcarbenoid intermediate. This species then undergoes a 1,2-hydride shift followed by elimination of lithium chloride, analogous to the mechanism proposed by Köbrich (Scheme 80B). Collectively, these studies underscore the reluctance of alkenyl chlorides – unlike their bromide counterparts – to undergo
<figure><img src="image_278.png" /><figcaption>B) Müller (2025) [153]</figcaption></figure>

<figure><img src="image_279.png" /><figcaption>**Scheme 76:** Alkyne synthesis by elimination of alkenyl chlorides.</figcaption></figure>

<figure><img src="image_280.png" /><figcaption>B) Cl → Na; Flaming (1980) [221]</figcaption></figure>

<figure><img src="image_281.png" /><figcaption>C) Cl → Mg; Jung (1982) [53]</figcaption></figure>

<figure><img src="image_282.png" /><figcaption>**Scheme 77:** Reductive lithiation of akenyl chlorides.</figcaption></figure>

halogen-lithium exchange. Instead, they preferentially engage in pathways involving either deprotonation or addition reactions.

In 1974, Köbrich showed that chloroalkenes possessing a γ-hydrogen can undergo cyclization by C–H insertion of the

corresponding carbenoid (Scheme 81A) [228]. This reaction was subsequently utilized in the context of several total syntheses, for example as illustrated by Taber for the synthesis of (+)-cassiol (e.g., Scheme 81B) [229]. The chemistry of these carbenoid C–H insertions was reviewed by Marek, Knorr, and Grainger [230-232].
A) Wittig (1941) [222]

<figure><img src="image_283.png" /></figure>

135

PhLi (2 equiv)
or
*n*-BuLi (2 equiv)

<figure><img src="image_284.png" /></figure>

<figure><img src="image_285.png" /></figure>

434

98%

<figure><img src="image_286.png" /></figure>

345

2%

B) Schlosser (1967) [223,224]

<figure><img src="image_287.png" /></figure>

E-135

<figure><img src="image_288.png" /></figure>

RLi

<figure><img src="image_289.png" /></figure>

E-435

<figure><img src="image_290.png" /></figure>

RLi

<figure><img src="image_291.png" /></figure>

434

<figure><img src="image_292.png" /></figure>

Z-135

<figure><img src="image_293.png" /></figure>

Z-435

C) Linstrumelle (1995) [225]

<figure><img src="image_294.png" /></figure>

245

$n$-BuLi (1.2 equiv)
THF, Et₂O, pentane
-100 °C, 30 min

<figure><img src="image_295.png" /></figure>

436

<figure><img src="image_296.png" /></figure>

<figure><img src="image_297.png" /></figure>

437

78% yield

<figure><img src="image_298.png" /></figure>

438

15% yield

<figure><img src="image_299.png" /><figcaption>**Scheme 78:** Reactions of alkenyl chlorides with organolithium reagents.</figcaption></figure>

A

B

C

D

<figure><img src="image_300.png" /></figure>

439

-108 °C, 45 min
A/C/D = 14:86:0

-12 °C, 5 min
A/C/D = 0:38:62

<figure><img src="image_301.png" /></figure>

344

-108 °C, 45 min
A/C/D = 14:86:0

-43 °C, 20 min
A/C/D = 0:0:100

<figure><img src="image_302.png" /></figure>

440

-108 °C, 35 min
A/C/D = 33:67:0

-72 °C, 65 min
A/C/D = 0:2:98

<figure><img src="image_303.png" /></figure>

441

-108 °C, 45 min
A/C/D = 92:8:0

-72 °C, 45 min
A/C/D = 65:15:30

<figure><img src="image_304.png" /><figcaption>**Scheme 79:** Reactions of alkenyl chlorides with organolithium reagents.</figcaption></figure>
<figure><img src="image_305.png" /><figcaption>**Scheme 80:** Addition-elimination reaction of alkenyl chloride 9 with organolithium reagents.</figcaption></figure>

<figure><img src="image_306.png" /><figcaption>**Scheme 81:** C–H insertions of lithiumcarbenoids.</figcaption></figure>

## 2.4 Coupling reactions

**Pd-catalyzed coupling reactions:** As transition-metal-catalyzed coupling reactions have been discussed in chapter 1.7, this section highlights only selected complementary examples. While alkenyl chlorides are generally less reactive than their

iodide or bromide counterparts [233], numerous successful palladium-catalyzed couplings with alkyl, alkenyl, aryl, and alkynyl nucleophiles have been reported. Representative cases are shown in Scheme 82 [176,203,214,234–236]. Sonogashira couplings of alkenyl chlorides are generally limited to (E)- or
A) alkyl coupling partner (Feringa, 2012) [203]

<figure><img src="image_307.png" /></figure>

B) alkene coupling partner (Linstrumelle, 1981) [176]

<figure><img src="image_308.png" /></figure>

C) alkene coupling partner (Hoveyda and Schrock, 2020) [235]

<figure><img src="image_309.png" /></figure>

D) aryl coupling partner (Wang, 2017) [214]

<figure><img src="image_310.png" /></figure>

E) alkyne coupling partner (Linstrumelle, 1985) [234]

<figure><img src="image_311.png" /></figure>

F) alkyne coupling partner (Hoveyda and Schrock, 2022) [236]

<figure><img src="image_312.png" /></figure>

G) boron coupling partner (Luo, 2024) [239]

<figure><img src="image_313.png" /><figcaption>**Scheme 82:** Pd-catalyzed coupling reactions with alkenyl chlorides as coupling partner.</figcaption></figure>
(Z)-1,2-dichloroethylenes and conjugated systems, where Pd(PPh₃)₄ gives good results (see Scheme 51C). However, in most other cases, alkenyl chlorides are significantly less reactive than their bromide or iodide analogues. In 1991, Linstrumelle and co-workers addressed this limitation by introducing a PdCl₂(PhCN)₂/CuI system in piperidine, enabling efficient coupling [237,238]. This catalytic system was recently applied by Hoveyda and Schrock (Scheme 82F) [236].

In 2024, Luo and co-workers reported a palladium-catalyzed synthesis of cyclic alkenylboronates from alkenyl chlorides (Scheme 82G) [239].

**Ni-catalyzed coupling reactions:** Alexakis, Normant, and Fugier reported the synthesis of compound **471** – the principal odoriferous component of Galbanum essential oil – via a nickel-catalyzed coupling between alkenyl chloride **183** and the corresponding alkenylcopper reagent (Scheme 83) [130]. Additional Ni-catalyzed coupling reactions with metalated arenes were outlined in Scheme 50.

Kurahashi recently reported a nickel-photoredox-catalyzed stereoconvergent coupling of alkenyl chlorides with nitrogen heterocycles, including one isolated example with alkenyl chloride **473** (Scheme 84) [240]. Notably, this substrate required a seven-fold longer reaction time compared to the corresponding bromides and iodides.

**Electrochemical coupling reactions:** It should be noted, that the use of alkenyl chlorides in electrochemical coupling reactions was recently reviewed by Marjani and co-workers (not shown) [241].

## 2.5 Miscellaneous applications

Weinreb and co-workers demonstrated that α-chloroketones can be synthesized from alkenyl chlorides by reaction with aqueous sodium hypochlorite in AcOH/acetone (Scheme 85) [242].

Jiang and co-workers introduced tetrahalogenoferrate(III) complexes as a new class of iron photocatalysts (Scheme 86) [243]. Prepared from FeCl₃ and simple bromide salts, these complexes show tunable photosensitivity in the visible range. Their distinct reactivity compared to FeCl₃ enables aerobic oxidative transposition of alkenyl chlorides, providing α-chloroketones in high efficiency under mild conditions and with broad scope.

Kuriyama and Onomura developed a Pd-catalyzed deutero-dechlorination of alkenyl chlorides (Scheme 87) [56]. The method enables precise incorporation of deuterium, tolerates heterocycles and drug-derived scaffolds, and was demonstrated on gram scale for a deuterated iminostilbene core.

In 2019, Shi and Cao reported a radical-promoted reaction of alkenyl chlorides with aliphatic and aromatic thiols to provide alkenyl sulfides (Scheme 88) [244].

<figure><img src="image_314.png" /><figcaption>**Scheme 83:** Ni-catalyzed coupling of alkenylcopper reagent with alkenyl chloride **183**.</figcaption></figure>

<figure><img src="image_315.png" /><figcaption>**Scheme 84:** Ni-catalyzed coupling of heterocycle **472** with alkenyl chloride **473**.</figcaption></figure>
<figure><img src="image_316.png" /></figure>

<figure><img src="image_317.png" /></figure>

<figure><img src="image_318.png" /></figure>

<figure><img src="image_319.png" /></figure>

**475**
72% yield

<figure><img src="image_320.png" /></figure>

**476**
82% yield

<figure><img src="image_321.png" /></figure>

**477**
99% yield

<figure><img src="image_322.png" /></figure>

**478**
66% yield

<figure><img src="image_323.png" /></figure>

**479**
81% yield

<figure><img src="image_324.png" /></figure>

**480**
52% yield

<figure><img src="image_325.png" /><figcaption>**Scheme 85:** Synthesis of α-chloroketones by oxidation of alkenyl chlorides.</figcaption></figure>

<figure><img src="image_326.png" /></figure>

<figure><img src="image_327.png" /></figure>

<figure><img src="image_328.png" /></figure>

**10**
80% yield

<figure><img src="image_329.png" /></figure>

**481**
72% yield

<figure><img src="image_330.png" /></figure>

**482**
77% yield

<figure><img src="image_331.png" /></figure>

**483**
54% yield

<figure><img src="image_332.png" /></figure>

**484**
87% yield

<figure><img src="image_333.png" /></figure>

**485**
74% yield

<caption>**Scheme 86:** Tetrahalogenoferrate(III)-promoted oxidation of alkenyl chlorides.</caption>

A) deuterodechlorination of alkenyl chlorides

<figure><img src="image_334.png" /></figure>

(1.0 equiv)

<figure><img src="image_335.png" /></figure>

**486**
(1.1 equiv)

**487** (2–6 mol %)

[Pd(allyl)Cl]₂ (1–3 mol %)

t-BuOK or Cs₂CO₃ (1.5–2.0 equiv)

toluene, 90 °C, 16 h

(12 examples)

<figure><img src="image_336.png" /></figure>

**487**

<figure><img src="image_337.png" /></figure>

B) proposed mechanism

<figure><img src="image_338.png" /><figcaption>**Scheme 87:** Chlorine-deuterium exchange promoted by a palladium catalyst.</figcaption></figure>
<figure><img src="image_339.png" /><figcaption>**Scheme 88:** Reaction of alkenyl chlorides with thiols in the presence of AIBN (azobisisobutyronitrile).</figcaption></figure>

Chloroalkene annulations (Scheme 89) were reviewed by Lansbury several decades ago [245]. These transformations involve the intramolecular reaction of chloroalkene nucleophiles with in situ-generated tertiary or benzylic carbocations. The resulting cationic intermediate **B** typically provides the corresponding ketone after aqueous work-up.

<figure><img src="image_340.png" /><figcaption>**Scheme 89:** Chloroalkene annulation.</figcaption></figure>

## Conclusion

This review represents my attempt to classify and structure the rapidly growing field of alkenyl chloride chemistry. I do not claim full coverage, yet I believe that the key reactions have been included to guide future work and help authors identify prior contributions. My survey also revealed that many recent publications overlooked related studies, and the true extent of this field remains underappreciated. While the synthesis of alkenyl chlorides is versatile, their synthetic applications – beyond Pd-catalyzed couplings – are still underdeveloped, offering ample opportunities for future synthetic discoveries.

## Acknowledgements

The author expresses sincere gratitude to former master 1 student Louann Maillet for conducting the kinetic studies presented in Figure 5 and Figure 7.

## Funding

This work was supported by the Agence Nationale de la Recherche (ANR-21-CE07-0005-01 CatCoupling), the Centre National de la Recherche Scientifique (CNRS) and the Université de Rennes.

## ORCID® iDs

Daniel S. Müller - https://orcid.org/0000-0001-8184-1474

## Data Availability Statement

Data sharing is not applicable as no new data was generated or analyzed in this study.

## References

1. Salameh, E.; Tarawneh, A.; Al-Raggad, M. *Arabian J. Geosci.* **2016**, *9*, 414. doi:10.1007/s12517-016-2431-9

2. Roche, L.; Muhl, M.; Finkbeiner, M. *Int. J. Life Cycle Assess.* **2023**, *28*, 1132–1141. doi:10.1007/s11367-023-02200-x

3. Zhukova, N. V.; Gloriozova, T. A.; Poroikov, V. V.; Dembitsky, V. M. *Pharma Innovation J.* **2017**, *6*, 456–462.

4. Bidleman, T. F.; Andersson, A.; Jantunen, L. M.; Kucklick, J. R.; Kylin, H.; Letcher, R. J.; Tysklind, M.; Wong, F. *Emerging Contam.* **2019**, *5*, 89–115. doi:10.1016/j.emcon.2019.02.007

5. Neumann, C. S.; Fujimori, D. G.; Walsh, C. T. *Chem. Biol.* **2008**, *15*, 99–109. doi:10.1016/j.chembiol.2008.01.006

6. Fang, W.-Y.; Ravindar, L.; Rakesh, K. P.; Manukumar, H. M.; Shantharam, C. S.; Alharbi, N. S.; Qin, H.-L. *Eur. J. Med. Chem.* **2019**, *173*, 117–153. doi:10.1016/j.ejmech.2019.03.063

7. Jayaraj, R.; Megha, P.; Sreedev, P. *Interdiscip. Toxicol.* **2016**, *9*, 90–100. doi:10.1515/intox-2016-0012

8. Matsumura, Y.; Aoyagi, S.; Kibayashi, C. *Org. Lett.* **2004**, *6*, 965–968. doi:10.1021/ol0301431

9. Hayakawa, I.; Ueda, M.; Yamaura, M.; Ikeda, Y.; Suzuki, Y.; Yoshizato, K.; Kigoshi, H. *Org. Lett.* **2008**, *10*, 1859–1862. doi:10.1021/ol800554f

10. Malloy, K. L.; Suyama, T. L.; Engene, N.; Debonsi, H.; Cao, Z.; Matalainaho, T.; Spadafora, C.; Murray, T. F.; Gerwick, W. H. *J. Nat. Prod.* **2012**, *75*, 60–66. doi:10.1021/np200611f

11. Nunnery, J. K.; Engene, N.; Byrum, T.; Cao, Z.; Jabba, S. V.; Pereira, A. R.; Matalainaho, T.; Murray, T. F.; Gerwick, W. H. *J. Org. Chem.* **2012**, *77*, 4198–4208. doi:10.1021/jo300160e

12. Stierle, D. B.; Wing, R. M.; Sims, J. J. *Tetrahedron Lett.* **1976**, *17*, 4455–4458. doi:10.1016/0040-4039(76)80141-4

13. Montaser, R.; Paul, V. J.; Luesch, H. *Org. Lett.* **2013**, *15*, 4050–4053. doi:10.1021/ol401396u

14. Ando, H.; Ueoka, R.; Okada, S.; Fujita, T.; Iwashita, T.; Imai, T.; Yokoyama, T.; Matsumoto, Y.; van Soest, R. W. M.; Matsunaga, S. *J. Nat. Prod.* **2010**, *73*, 1947–1950. doi:10.1021/np1003565

15. Bucher, C.; Deans, R. M.; Burns, N. Z. *J. Am. Chem. Soc.* **2015**, *137*, 12784–12787. doi:10.1021/jacs.5b08398

16. Hayakawa, I.; Suzuki, K.; Okamura, M.; Funakubo, S.; Onozaki, Y.; Kawamura, D.; Ohyoshi, T.; Kigoshi, H. *Org. Lett.* **2017**, *19*, 5713–5716. doi:10.1021/acs.orglett.7b03009

17. Chen, J.; Fu, X.-G.; Zhou, L.; Zhang, J.-T.; Qi, X.-L.; Cao, X.-P. *J. Org. Chem.* **2009**, *74*, 4149–4157. doi:10.1021/jo9003103

18. Stratmann, K.; Moore, R. E.; Bonjouklian, R.; Deeter, J. B.; Patterson, G. M. L.; Shaffer, S.; Smith, C. D.; Smitka, T. A. *J. Am. Chem. Soc.* **1994**, *116*, 9935–9942. doi:10.1021/ja00101a015

19. Mynderse, J. S.; Faulkner, D. J. *J. Am. Chem. Soc.* **1974**, *96*, 6771–6772. doi:10.1021/ja00828a045

20. Edwards, D. J.; Marquez, B. L.; Nogle, L. M.; McPhail, K.; Goeger, D. E.; Roberts, M. A.; Gerwick, W. H. *Chem. Biol.* **2004**, *11*, 817–833. doi:10.1016/j.chembiol.2004.03.030
21. Pettit, G. R.; Chicac, Z. A.; Gao, F.; Herald, C. L.; Boyd, M. R.; Schmidt, J. M.; Hooper, J. N. *J. Org. Chem.* **1993**, *58*, 1302–1304.
doi:10.1021/jo00058a004

22. Renner, M. K.; Jensen, P. R.; Fenical, W. *J. Org. Chem.* **1998**, *63*,
8346–8354. doi:10.1021/jo981226b

23. Matthew, S.; Salvador, L. A.; Schupp, P. J.; Paul, V. J.; Luesch, H.
*J. Nat. Prod.* **2010**, *73*, 1544–1552. doi:10.1021/np1004032

24. Engler, M.; Anke, T.; Sterner, O.; Brandt, U. *J. Antibiot.* **1997**, *50*,
325–329. doi:10.7164/antibiotics.50.325

25. Palopoli, F. P.; Feil, V. J.; Allen, R. E.; Holtkamp, D. E.; Richardson, A. *J. Med. Chem.* **1967**, *10*, 84–86.
doi:10.1021/jm00313a017

26. McLAMORE, W. M.; P'AN, S. Y.; BAVLEY, A. *J. Org. Chem.* **1955**, *20*,
109–117. doi:10.1021/jo01119a018

27. Hebert, A. A.; Sigman, E. S.; Levy, M. L. *J. Am. Acad. Dermatol.* **1991**,
25, 805–808. doi:10.1016/s0190-9622(08)80973-5

28. Watson, K. G. *Aust. J. Chem.* **2011**, *64*, 367–372.
doi:10.1071/ch10366

29. Jacobs, T. *L. Org. React.* **1949**, *5*, 1–78.

30. Pohland, A. E.; Benson, W. R. *Chem. Rev.* **1966**, *66*, 161–197.
doi:10.1021/cr60240a003

31. Denton, E. H.; Stepanović, O.; Morandi, B. *Chem. – Eur. J.* **2024**, *30*,
e202401852. doi:10.1002/chem.202401852

32. Saini, P.; Jyoti; Sharma, P. K.; Singh, V. *Eur. J. Org. Chem.* **2025**, *28*,
e202401058. doi:10.1002/ejoc.202401058

33. Guinchard, X.; Roulland, E. *Synlett* **2011**, 2779–2788.
doi:10.1055/s-0031-1289862

34. Takai, K.; Nitta, K.; Utimoto, K. *J. Am. Chem. Soc.* **1986**, *108*,
7408–7410. doi:10.1021/ja00283a046

35. Takai, K. *Organochromium Reagents. In Comprehensive Organic
Synthesis*, 2nd ed.; Knochel, P., Ed.; Elsevier: Amsterdam,
Netherlands, 2014; pp 159–203.
doi:10.1016/b978-0-08-097742-3.00108-7

36. Petrone, D. A.; Ye, J.; Lautens, M. *Chem. Rev.* **2016**, *116*,
8003–8104. doi:10.1021/acs.chemrev.6b00089

37. Evano, G.; Nitelet, A.; Thilmany, P.; Dewez, D. F. *Front. Chem.* (*Lausanne, Switz.*) **2018**, *6*, 114.
doi:10.3389/fchem.2018.00114

38. Varenikov, A.; Shapiro, E.; Gandelman, M. *Chem. Rev.* **2021**, *121*,
412–484. doi:10.1021/acs.chemrev.0c00813

39. Hoveyda, A. H.; Qin, C.; Sui, X. Z.; Liu, Q.; Li, X.; Nikbakht, A. *Acc. Chem. Res.* **2023**, *56*, 2426–2446.
doi:10.1021/acs.accounts.3c00341

40. Chen, J.; Wei, W.-T.; Li, Z.; Lu, Z. *Chem. Soc. Rev.* **2024**, *53*,
7566–7589. doi:10.1039/d4cs00167b

41. Iwai, K.; Nishiwaki, N. *Adv. Synth. Catal.* **2024**, *366*, 1950–1964.
doi:10.1002/adsc.202301499

42. Urch, C. J. Vinyl and Aryl Halides. In *Comprehensive Organic Functional Group Transformations II: Carbon with One Heteroatom Attached by a Single Bond*; Katritzky, A. R.; Taylor, R. J. K., Eds.; Elsevier: Amsterdam, Netherlands, 1995; pp 605–633.
doi:10.1016/b0-08-044705-8/00252-1

43. Xu, L.; Zhang, J.; Tao, C.; Cao, X. *Prog. Chem.* **2013**, *25*, 1876–1887.

44. Chelucci, G. *Chem. Rev.* **2012**, *112*, 1344–1462.
doi:10.1021/cr200165q

45. Friedel, C. *C. R. Hebd. Seances Acad. Sci.* **1868**, *67*, 1192.

46. Henry, L. *Ber. Dtsch. Chem. Ges.* **1875**, *8*, 398–416.
doi:10.1002/cber.187500801129

47. Faworsky, A. *J. Prakt. Chem.* **1913**, *88*, 641–698.
doi:10.1002/prac.19130880148

48. Kagan, J.; Arora, S. K.; Bryzgis, M.; Dhawan, S. N.; Reid, K.; Singh, S. P.; Tow, L. *J. Org. Chem.* **1983**, *48*, 703–706.
doi:10.1021/jo00153a016

49. Schmidt, S. E.; Salvatore, R. N.; Jung, K. W.; Kwon, T. *Synlett* **1999**,
1948–1950. doi:10.1055/s-1999-2985

50. Ghaffarzadeh, M.; Bolourchtian, M.; Fard, Z. H.; Halvagar, M. R.; Mohsenzadeh, F. *Synth. Commun.* **2006**, *36*, 1973–1981.
doi:10.1080/00397910600634100

51. Hadida-Ruah, S. S.; Groothenhuis, P. D. J.; van Goor, F. F.; Zhou, J.; Bear, B. R.; Miller, M. T.; McCartney, J.; Numa, M. M. D.; Yang, X.; Nair, N. Modulators of atp-binding cassette transporters. U.S. Pat. Appl. US 2016/0271105 A1, Sept 22, 2016.

52. Scott, L. T.; Cheng, P.-C.; Hashemi, M. M.; Bratcher, M. S.; Meyer, D. T.; Warren, H. B. *J. Am. Chem. Soc.* **1997**, *119*, 10963–10968. doi:10.1021/ja972019g

53. Jung, M. E.; Light, L. A. *J. Org. Chem.* **1982**, *47*, 1084–1090.
doi:10.1021/jo00345a038

54. Adam, W.; Richter, M. *J. Synthesis* **1994**, 176–180.
doi:10.1055/s-1994-25433

55. Fujihara, T.; Nogi, K.; Xu, T.; Terao, J.; Tsuji, Y. *J. Am. Chem. Soc.* **2012**, *134*, 9106–9109. doi:10.1021/ja303514b

56. Kuriyama, M.; Yano, G.; Kiba, H.; Morimoto, T.; Yamamoto, K.; Demizu, Y.; Onomura, O. *Org. Process Res. Dev.* **2019**, *23*, 1552–1557. doi:10.1021/acs.oprd.9b00193

57. Carroll, B.; Kubler, D. G.; Davis, H. W.; Whaley, A. M. *J. Am. Chem. Soc.* **1951**, *73*, 5382–5383. doi:10.1021/ja01155a107

58. Engler, T. A.; Combrink, K. D.; Ray, J. E. *Synth. Commun.* **1989**, *19*,
1735–1744. doi:10.1080/00397918908051073

59. Nagendrappa, G. *Synthesis* **1980**, 704–706.
doi:10.1055/s-1980-29178

60. Harding, K. E.; Tseng, C.-Y. *J. Org. Chem.* **1978**, *43*, 3974–3977.
doi:10.1021/jo00414a042

61. Heller, B.; Gutnov, A.; Fischer, C.; Drexler, H.-J.; Spannenberg, A.; Redkin, D.; Sundermann, C., Sundermann, B. *Chem. – Eur. J.* **2007**, *13*, 1117–1128. doi:10.1002/chem.200600826

62. Gross, H.; Gloede, J. *Chem. Ber.* **1963**, *96*, 1387–1394.
doi:10.1002/cber.19630960530

63. Hudrlak, P. F.; Kulkarni, A. K. *Tetrahedron* **1985**, *41*, 1179–1182.
doi:10.1016/s0040-4020(01)96518-4

64. Spaggiari, A.; Vaccari, D.; Davoli, P.; Torre, G.; Prati, F. *J. Org. Chem.* **2007**, *72*, 2216–2219. doi:10.1021/jo061346g

65. Horner, L.; Oediger, H.; Hoffmann, H. *Justus Liebigs Ann. Chem.* **1959**, *62*, 26–34. doi:10.1002/jlac.19596260104

66. Kamei, K.; Maeda, N.; Tatsuoka, T. *Tetrahedron Lett.* **2005**, *46*,
229–232. doi:10.1016/j.tetlet.2004.11.075

67. Al-awar, R. S.; Joseph, S. P.; Comins, D. L. *J. Org. Chem.* **1993**, *58*,
7732–7739. doi:10.1021/jo00079a018

68. Lilienkampf, A.; Johansson, M. P.; Wähälä, K. *Org. Lett.* **2003**, *5*,
3387–3390. doi:10.1021/ol034914c

69. Rey, A. W.; Keshava Murthy, K. S. Novel process for the preparation of alpha-chlorovinyl, alpha, alpha-dichloro, and acetylenes from ketones. Can. Pat. Appl. CA2, 510, 093 A1, Dec 16, 2006.

70. Eszenyi, T.; Timár, T.; Sebők, P. *Tetrahedron Lett.* **1991**, *32*,
827–828. doi:10.1016/s0040-4039(00)74898-2

71. Moughamir, K.; Mezgueldi, B.; Atmani, A.; Mestdagh, H.; Rolando, C. *Tetrahedron Lett.* **1999**, *40*, 59–62.
doi:10.1016/s0040-4039(98)80019-1

72. Kodomari, M.; Nagaoka, T.; Furusawa, Y. *Tetrahedron Lett.* **2001**, *42*,
3105–3107. doi:10.1016/s0040-4039(01)00378-1
73. Ganiu, M. O.; Nepal, B.; Van Houten, J. P.; Kartika, R. *Tetrahedron* **2020**, *76*, 131553. doi:10.1016/j.tet.2020.131553

74. Su, W.; Jin, C. *Org. Lett.* **2007**, *9*, 993–996. doi:10.1021/ol062991c

75. Cotarca, L.; Geller, T.; Répási, J. *Org. Process Res. Dev.* **2017**, *21*, 1439–1446. doi:10.1021/acs.oprd.7b00220

76. Quasdorf, K. W.; Achmatowicz, M.; Ananthoji, P.; Bolger, J.; Brown, D. B.; Caille, S.; Chen, J.; Chen, Y.; Cochran, B. M.; Colyer, J. T.; Corbett, M.; Dai, X.-J.; Dalbey, B.; Dan, Y.; Griffin, D. J.; Han, Y.; Hsieh, H.-W.; Liu, K.; Lopez-Mejias, V.; Powazinik, W., IV; Robinson, J. A.; Smith, A.; Stahl, A. E.; Tedrow, J. S.; Shi, T.; Silva Elipe, M. V.; Visontai, L.; Wang, Z.; Parsons, A. T. *Org. Process Res. Dev.* **2025**, *29*, 1456–1464. doi:10.1021/acs.oprd.5c00043

77. Saputra, M. A.; Ngo, L.; Kartika, R. *J. Org. Chem.* **2015**, *80*, 8815–8820. doi:10.1021/acs.joc.5b01137

78. Shen, X.; Hyde, A. M.; Buchwald, S. L. *J. Am. Chem. Soc.* **2010**, *132*, 14076–14078. doi:10.1021/ja107481a

79. Pan, J.; Wang, X.; Zhang, Y.; Buchwald, S. L. *Org. Lett.* **2011**, *13*, 4974–4976. doi:10.1021/ol202098h

80. Shirakawa, E.; Imazaki, Y.; Hayashi, T. *Chem. Commun.* **2009**, 5088–5090. doi:10.1039/b907761h

81. Imazaki, Y.; Shirakawa, E.; Ueno, R.; Hayashi, T. *J. Am. Chem. Soc.* **2012**, *134*, 14760–14763. doi:10.1021/ja307771d

82. Plaçais, C.; Kaldas, S. J.; Donnard, M.; Panossian, A.; Bernier, D.; Pazenok, S.; Leroux, F. R. *Chem. – Eur. J.* **2023**, *29*, e202301420. doi:10.1002/chem.202301420

83. Hofstra, J. L.; Poremba, K. E.; Shimozono, A. M.; Reisman, S. E. *Angew. Chem., Int. Ed.* **2019**, *58*, 14901–14905. doi:10.1002/anie.201906815

84. Chen, M.-Y.; Charvet, S.; Payard, P.-A.; Perrin, M.-E. L.; Vantourout, J. C. *Angew. Chem., Int. Ed.* **2024**, *63*, e202311165. doi:10.1002/anie.202311165

85. Nitelet, A.; Evano, G. *Org. Lett.* **2016**, *18*, 1904–1907. doi:10.1021/acs.orglett.6b00678

86. Nitelet, A.; Jouvin, K.; Evano, G. *Tetrahedron* **2016**, *72*, 5972–5987. doi:10.1016/j.tet.2016.07.018

87. Ren, F.; Cheng, J.; Tian, J.; Wu, X.; Zhang, R.; Zhou, X.; Li, Z.; Li, C. *J. Catal.* **2025**, *442*, 115918. doi:10.1016/j.jcat.2024.115918

88. Qiao, X.; Zhao, Z.-H.; Zhang, J. *Catal. Sci. Technol.* **2024**, *14*, 3838–3852. doi:10.1039/d4cy00549j

89. Wei, S.; Lan, G.; Qiu, Y.; Lin, D.; Kong, W.; Li, Y. *Chin. J. Catal.* **2025**, *70*, 8–43. doi:10.1016/s1872-2067(24)60245-7

90. Krasnyakova, T. V.; Nikitenko, D. V.; Mitchenko, S. A. *Kinet. Catal.* **2020**, *61*, 58–79. doi:10.1134/s0023158420010036

91. Hennion, G. F.; Welsh, C. E. *J. Am. Chem. Soc.* **1940**, *62*, 1367–1368. doi:10.1021/ja01863a010

92. Fahey, R. C.; Payne, M. T.; Lee, D.-J. *J. Org. Chem.* **1974**, *39*, 1124–1130. doi:10.1021/jo00922a024

93. Marcuzzi, F.; Melloni, G. *J. Am. Chem. Soc.* **1976**, *98*, 3295–3300. doi:10.1021/ja00427a040

94. Kropp, P. J.; Crawford, S. D. *J. Org. Chem.* **1994**, *59*, 3102–3112. doi:10.1021/jo00090a031

95. Dérien, S.; Klein, H.; Bruneau, C. *Angew. Chem., Int. Ed.* **2015**, *54*, 12112–12115. doi:10.1002/anie.201505144

96. Xu, C.-X.; Ma, C.-H.; Xiao, F.-R.; Chen, H.-W.; Dai, B. *Chin. Chem. Lett.* **2016**, *27*, 1683–1685. doi:10.1016/j.cclet.2016.04.019

97. Yu, W.; Jin, Z. *J. Am. Chem. Soc.* **2000**, *122*, 9840–9841. doi:10.1021/ja000903s

98. Cao, W.; Chen, P.; Wang, L.; Wen, H.; Liu, Y.; Wang, W.; Tang, Y. *Org. Lett.* **2018**, *20*, 4507–4511. doi:10.1021/acs.orglett.8b01809

99. Zeng, X.; Lu, Z.; Liu, S.; Hammond, G. B.; Xu, B. *J. Org. Chem.* **2017**, *82*, 13179–13187. doi:10.1021/acs.joc.7b02257

100. Pati, S. S.; Mishra, A.; Das, J. P. *J. Org. Chem.* **2024**, *89*, 1727–1735. doi:10.1021/acs.joc.3c02436

101. Mulder, J. A.; Kurtz, K. C. M.; Hsung, R. P.; Coverdale, H.; Frederick, M. O.; Shen, L.; Zificsak, C. A. *Org. Lett.* **2003**, *5*, 1547–1550. doi:10.1021/ol0300266

102. Prabagar, B.; Nayak, S.; Mallick, R. K.; Prasad, R.; Sahoo, A. K. *Org. Chem. Front.* **2016**, *3*, 110–115. doi:10.1039/c5q000345h

103. Sun, A.; Huang, X. *Synthesis* **2000**, 1819–1821. doi:10.1055/s-2000-8233

104. Yang, Z.; Chen, X.; Kong, W.; Xia, S.; Zheng, R.; Luo, F.; Zhu, G. *Org. Biomol. Chem.* **2013**, *11*, 2175–2185. doi:10.1039/c3ob27307e

105. Ma, S.; Lu, X.; Li, Z. *J. Org. Chem.* **1992**, *57*, 709–713. doi:10.1021/jo00028a055

106. Dupont, J.; Basso, N. R.; Meneghetti, M. R.; Konrath, R. A.; Burrow, R.; Horner, M. *Organometallics* **1997**, *16*, 2386–2391. doi:10.1021/om970064r

107. Derosa, J.; Cantu, A. L.; Boulous, M. N.; O'Duill, M. L.; Turnbull, J. L.; Liu, Z.; De La Torre, D. M.; Engle, K. M. *J. Am. Chem. Soc.* **2017**, *139*, 5183–5193. doi:10.1021/jacs.7b00892

108. Ma, S.; Lu, X. *J. Org. Chem.* **1993**, *58*, 1245–1250. doi:10.1021/jo00057a043

109. Li, X.; Shi, X.; Fang, M.; Xu, X. *J. Org. Chem.* **2013**, *78*, 9499–9504. doi:10.1021/jo401581n

110. Wang, W.; Liu, L.; Chang, W.; Li, J. *Chem. – Eur. J.* **2018**, *24*, 8542–8547. doi:10.1002/chem.201801262

111. Danielec, H.; Klügge, J.; Schlummer, B.; Bach, T. *Synthesis* **2006**, *551*–556. doi:10.1055/s-2005-918500

112. Nguyen, T. M.; Popek, L.; Matchavariani, D.; Blanchard, N.; Bizet, V.; Cahard, D. *Org. Lett.* **2024**, *26*, 365–369. doi:10.1021/acs.orglett.3c04043

113. Azzi, E.; Ghigo, G.; Sarasino, L.; Parisotto, S.; Moro, R.; Renzi, P.; Deagostino, A. *J. Org. Chem.* **2023**, *88*, 6420–6433. doi:10.1021/acs.joc.2c01963

114. Zweifel, G.; Lewis, W. *J. Org. Chem.* **1978**, *43*, 2739–2744. doi:10.1021/jo00408a001

115. Ramazanov, I. R.; Kadikova, R. N.; Dzhemilev, U. M. *Russ. J. Org. Chem.* **2013**, *49*, 321–326. doi:10.1134/s1070428013030020

116. Masuda, Y.; Hoshi, M.; Arase, A. *J. Chem. Soc., Perkin Trans. 1* **1992**, 2725–2726. doi:10.1039/p19920002725

117. Petasis, N. A.; Zavialov, I. A. *Tetrahedron Lett.* **1996**, *37*, 567–570. doi:10.1016/0040-4039(95)02262-7

118. Molander, G. A.; Cavalcanti, L. N. *J. Org. Chem.* **2011**, *76*, 7195–7203. doi:10.1021/jo201313a

119. Levy, A. B.; Talley, P.; Dunford, J. A. *Tetrahedron Lett.* **1977**, *18*, 3545–3548. doi:10.1016/s0040-4039(01)83288-3

120. Kigoshi, H.; Kita, M.; Ogawa, S.; Itoh, M.; Uemura, D. *Org. Lett.* **2003**, *5*, 957–960. doi:10.1021/ol0341804

121. Graf, K. M.; Tabor, M. G.; Brown, M. L.; Paige, M. *Org. Lett.* **2009**, *11*, 5382–5385. doi:10.1021/ol9021222

122. Cui, C.; Dai, W.-M. *Org. Lett.* **2018**, *20*, 3358–3361. doi:10.1021/acs.orglett.8b01269

123. Hart, D. W.; Blackburn, T. F.; Schwartz, J. *J. Am. Chem. Soc.* **1975**, *97*, 679–680. doi:10.1021/ja00836a056
124. Deloux, L.; Skrzypczak-Jankun, E.; Cheesman, B. V.; Srebnik, M.; Sabat, M. *J. Am. Chem. Soc.* **1994**, *116*, 10302–10303.
doi:10.1021/ja00101a061

125. Biltz, H. *Justus Liebigs Ann. Chem.* **1897**, *296*, 263–278.
doi:10.1002/jlac.18972960302

126. Dolby, L. J. *J. Org. Chem.* **1962**, *27*, 2971–2975.
doi:10.1021/jo01056a001

127. Miller, R. B.; McGarvey, G. *J. Org. Chem.* **1978**, *43*, 4424–4431.
doi:10.1021/jo00417a006

128. Miller, R. B.; McGarvey, G. *Synth. Commun.* **1977**, *7*, 475–482.
doi:10.1080/00397917708050783

129. Kunda, S. A.; Smith, T. L.; Hylarides, M. D.; Kabalka, G. W. *Tetrahedron Lett.* **1985**, *26*, 279–280.
doi:10.1016/s0040-4039(01)80796-6

130. Alexakis, A.; Barthel, A.-M.; Normant, J. F.; Fugier, C.; Leroux, M. *Synth. Commun.* **1992**, *22*, 1839–1844.
doi:10.1080/00397919208021314

131. Tarchini, C.; An, T. D.; Jan, G.; Schlosser, M. *Helv. Chim. Acta* **1979**, *62*, 635–640. doi:10.1002/hlca.19790620230

132. Schlosser, M.; An, T. D. *Helv. Chim. Acta* **1979**, *62*, 1194–1198.
doi:10.1002/hlca.19790620428

133. Banwell, M. G.; Phillis, A. T.; Willis, A. C. *Org. Lett.* **2006**, *8*,
5341–5344. doi:10.1021/ol062224d

134. Puschnig, J.; Greatrex, B. W. *Eur. J. Org. Chem.* **2024**, *27*,
e202400031. doi:10.1002/ejoc.202400031

135. Kim, K.-M.; Park, I.-H. *Synthesis* **2004**, 2641–2644.
doi:10.1055/s-2004-831232

136. Xie, Y.; Zhang, Z.; Zhang, B.; He, N.; Peng, M.; Song, S.; Wang, B.; Yu, F. *J. Org. Chem.* **2024**, *89*, 8521–8530.
doi:10.1021/acs.joc.c400456

137. Yin, J.; Gallis, C. E.; Chisholm, J. D. *J. Org. Chem.* **2007**, *72*,
7054–7057. doi:10.1021/jo0711992

138. Gonzalez-de-Castro, A.; Xiao, J. *J. Am. Chem. Soc.* **2015**, *137*,
8206–8218. doi:10.1021/jacs.5b03956

139. Engman, L. *Tetrahedron Lett.* **1987**, *28*, 1463–1466.
doi:10.1016/s0040-4039(00)95954-9

140. Wang, J.; Ogawa, Y.; Shibata, N. *Sci. Rep.* **2019**, *9*, 19113.
doi:10.1038/s41598-019-55206-7

141. Lansbergen, B.; Meister, C. S.; McLeod, M. C. *Beilstein J. Org. Chem.* **2021**, *17*, 404–409. doi:10.3762/bjoc.17.36

142. Melloni, G.; Modena, G.; Tonellato, U. *Acc. Chem. Res.* **1981**, *14*,
227–233. doi:10.1021/ar00068a001

143. Maroni, R.; Melloni, G.; Modena, G. *J. Chem. Soc., Perkin Trans. 1* **1973**, 2491–2496. doi:10.1039/p19730002491

144. Mayr, H.; Gonzalez, J. L.; Lüdtke, K. *Chem. Ber.* **1994**, *127*, 525–531.
doi:10.1002/cber.19941270311

145. Mayr, H.; Striepe, W. *J. Org. Chem.* **1985**, *50*, 2995–2998.
doi:10.1021/jo00216a038

146. Kabalka, G. W.; Yao, M.-L.; Borella, S. *J. Am. Chem. Soc.* **2006**, *128*,
11320–11321. doi:10.1021/ja061379d

147. Yao, M.-L.; Quick, T. R.; Wu, Z.; Quinn, M. P.; Kabalka, G. W. *Org. Lett.* **2009**, *11*, 2647–2649. doi:10.1021/ol900669t

148. Creaser, C. S.; Creighton, J. A. *J. Chem. Soc., Dalton Trans.* **1975**,
1402–1405. doi:10.1039/dt9750001402

149. Biswas, S.; Maiti, S.; Jana, U. *Eur. J. Org. Chem.* **2009**, 2354–2359.
doi:10.1002/ejoc.200900104

150. Ren, K.; Wang, M.; Wang, L. *Eur. J. Org. Chem.* **2010**, 565–571.
doi:10.1002/ejoc.200901020

151. Liu, Z.-Q.; Wang, J.; Han, J.; Zhao, Y.; Zhou, B. *Tetrahedron Lett.* **2009**, *50*, 1240–1242. doi:10.1016/j.tetlet.2009.01.013

152. Sasaki, T.; Usuki, A.; Ohno, M. *J. Org. Chem.* **1980**, *45*, 3559–3564.
doi:10.1021/jo01306a004

153. Charki, P.; Müller, D. *S. ChemistrySelect* **2025**, *10*, e03325.
doi:10.1002/slct.202503325

154. Shi, J.-L.; Zhang, J.-C.; Wang, B.-Q.; Hu, P.; Zhao, K.-Q.; Shi, Z.-J. *Org. Lett.* **2016**, *18*, 1238–1241. doi:10.1021/acs.orglett.5b02472

155. Snyder, S. A.; Levinson, A. M. *Polyene Cyclizations. In Comprehensive Organic Synthesis*, 2nd ed.; Knochel, P., Ed.; Elsevier: Amsterdam, Netherlands, 2014; pp 268–292.
doi:10.1016/b978-0-08-097742-3.00309-8

156. Johnson, W. S.; Gravestock, M. B.; Parry, R. J.; Okorie, D. A. *J. Am. Chem. Soc.* **1972**, *94*, 8604–8605. doi:10.1021/ja00779a066

157. Alonso, P.; Pardo, P.; Fontaneda, R.; Fañanás, F. J.; Rodríguez, F. *Chem. – Eur. J.* **2017**, *23*, 13158–13163.
doi:10.1002/chem.201702490

158. Cook, G. R.; Hayashi, R. *Org. Lett.* **2006**, *8*, 1045–1048.
doi:10.1021/ol052802a

159. White, E. H.; Tiwari, H. P.; Todd, M. J. *J. Am. Chem. Soc.* **1968**, *90*, 4734–4736. doi:10.1021/ja01019a044

160. Lansbury, P. T.; Demmin, T. R.; DuBois, G. E.; Haddon, V. R. *J. Am. Chem. Soc.* **1975**, *97*, 394–403. doi:10.1021/ja00835a030

161. Mellor, M.; Santos, A.; Scovell, E. G.; Sutherland, J. K. *J. Chem. Soc., Chem. Commun.* **1978**, 528–529.
doi:10.1039/c39780000528

162. Johnson, W. S.; Ward, C. E.; Boots, S. G.; Gravestock, M. B.; Markezich, R. L.; McCarry, B. E.; Okorie, D. A.; Parry, R. J. *J. Am. Chem. Soc.* **1981**, *103*, 88–98. doi:10.1021/ja00391a017

163. Balog, A.; Geib, S. V.; Curran, D. P. *J. Org. Chem.* **1995**, *60*,
345–352. doi:10.1021/jo00107a012

164. Miranda, P. O.; Díaz, D. D.; Padrón, J. I.; Bermejo, J.; Martín, V. S. *Org. Lett.* **2003**, *5*, 1979–1982. doi:10.1021/ol034568z

165. Bhatti, N. H.; Salter, M. M. *Tetrahedron Lett.* **2004**, *45*, 8379–8382.
doi:10.1016/j.tetlet.2004.09.054

166. Sun, J.; Kozmin, S. *A. J. Am. Chem. Soc.* **2005**, *127*, 13512–13513.
doi:10.1021/ja055054t

167. Hou, J.; Yin, J.; Han, H.; Yang, Q.; Li, Y.; Lou, Y.; Wu, X.; You, Y. *Org. Lett.* **2023**, *25*, 4359–4365. doi:10.1021/acs.orglett.3c01495

168. Olivier, A.; Müller, D. S. *Org. Process Res. Dev.* **2024**, *28*, 305–309.
doi:10.1021/acs.oprd.3c00418

169. Müller, D. *S. Beilstein J. Org. Chem.* **2024**, *20*, 787–814.
doi:10.3762/bjoc.20.72

170. Alachouzos, G.; Frontier, A. J. *Angew. Chem., Int. Ed.* **2017**, *56*,
15030–15034. doi:10.1002/anie.201709482

171. Holt, C.; Alachouzos, G.; Frontier, A. J. *J. Am. Chem. Soc.* **2019**, *141*,
5461–5469. doi:10.1021/jacs.9b00198

172. Hernandez, J. J.; Frontier, A. J. *Org. Lett.* **2021**, *23*, 1782–1786.
doi:10.1021/acs.orglett.1c00191

173. Frontier, A. J.; Hernandez, J. J. *Acc. Chem. Res.* **2020**, *53*,
1822–1832. doi:10.1021/acs.accounts.0c00284

174. Corriu, R. J. P.; Masse, J. P. *J. Chem. Soc., Chem. Commun.* **1972**,
144a. doi:10.1039/c3972000144a

175. Tamao, K.; Sumitani, K.; Kumada, M. *J. Am. Chem. Soc.* **1972**, *94*,
4374–4376. doi:10.1021/ja00767a075

176. Ratovelomanana, V.; Linstrumelle, G. *Tetrahedron Lett.* **1981**, *22*,
315–318. doi:10.1016/0040-4039(81)80085-8

177. Sonogashira, K.; Tohda, Y.; Hagihara, N. *Tetrahedron Lett.* **1975**, *16*,
4467–4470. doi:10.1016/s0040-4039(00)91094-3

178. Organ, M. G.; Ghasemi, H.; Valente, C. *Tetrahedron* **2004**, *60*,
9453–9461. doi:10.1016/j.tet.2004.08.006
179. Qian, M.; Huang, Z.; Negishi, E.-i. *Org. Lett.* **2004**, *6*, 1531–1534.
doi:10.1021/ol049716f

180. Métay, E.; Hu, Q.; Negishi, E.-i. *Org. Lett.* **2006**, *8*, 5773–5776.
doi:10.1021/ol0623825

181. Matsuda, T.; Suzuki, K.; Miura, N. *Adv. Synth. Catal.* **2013**, *355*,
3396–3400. doi:10.1002/adsc.201300482

182. Minato, A.; Suzuki, K.; Tamao, K. *J. Am. Chem. Soc.* **1987**, *109*,
1257–1258. doi:10.1021/ja00238a052

183. Tan, Z.; Negishi, E.-i. *Angew. Chem., Int. Ed.* **2006**, *45*, 762–765.
doi:10.1002/anie.200503519

184. Barluenga, J.; Valdés, C.; Beltrán, G.; Escribano, M.; Aznar, F.
*Angew. Chem., Int. Ed.* **2006**, *45*, 6893–6896.
doi:10.1002/anie.200601045

185. Heinrich, M. R.; Blank, O.; Ullrich, D.; Kirschstein, M. *J. Org. Chem.*
**2007**, *72*, 9609–9616. doi:10.1021/jo701717k

186. Watanabe, Y.; Takagi, T.; Miyamoto, K.; Kanazawa, J.; Uchiyama, M.
*Org. Lett.* **2020**, *22*, 3469–3473. doi:10.1021/acs.orglett.0c00924

187. Macnaughtan, M. L.; Johnson, M. J. A.; Kampf, J. W.
*J. Am. Chem. Soc.* **2007**, *129*, 7708–7709. doi:10.1021/ja0715952

188. Macnaughtan, M. L.; Gary, J. B.; Gerlach, D. L.; Johnson, M. J. A.;
Kampf, J. W. *Organometallics* **2009**, *28*, 2880–2887.
doi:10.1021/om800463n

189. Sashuk, V.; Samojlowicz, C.; Szadkowska, A.; Grela, K.
*Chem. Commun.* **2008**, 2468–2470. doi:10.1039/b801687a

190. Grela, K.; Harutyunyan, S.; Michrowska, A. *Angew. Chem., Int. Ed.*
**2002**, *41*, 4038–4040.
doi:10.1002/1521-3773(20021104)41:21<4038::aid-anie4038>3.0.co;2-0

191. Nguyen, T. T.; Koh, M. J.; Shen, X.; Romiti, F.; Schrock, R. R.;
Hoveyda, A. H. *Science* **2016**, *352*, 569–575.
doi:10.1126/science.aaf4622

192. Koh, M. J.; Nguyen, T. T.; Zhang, H.; Schrock, R. R.; Hoveyda, A. H.
*Nature* **2016**, *531*, 459–465. doi:10.1038/nature17396

193. Mu, Y.; Nguyen, T. T.; van der Mei, F. W.; Schrock, R. R.;
Hoveyda, A. H. *Angew. Chem., Int. Ed.* **2019**, *58*, 5365–5370.
doi:10.1002/anie.201901132

194. Wittig, G.; Schlosser, M. *Chem. Ber.* **1961**, *94*, 1373–1383.
doi:10.1002/cber.19610940532

195. Miyano, S.; Izumi, Y.; Hashimoto, H. *J. Chem. Soc., Chem. Commun.*
**1978**, 446–447. doi:10.1039/c39780000446

196. Zheng, S.; Santosh Laxmi, Y. R.; David, E.; Dinkova-Kostova, A. T.;
Shiavoni, K. H.; Ren, Y.; Zheng, Y.; Trevino, I.; Bumeister, R.;
Ojima, I.; Wigley, W. C.; Bliska, J. B.; Mierke, D. F.; Honda, T.
*J. Med. Chem.* **2012**, *55*, 4837–4846. doi:10.1021/jm3003922

197. Zhang, X.-p.; Schlosser, M. *Tetrahedron Lett.* **1993**, *34*, 1925–1928.
doi:10.1016/s0040-4039(00)91964-6

198. Lebrun, M.-E.; Le Marquand, P.; Berthelette, C. *J. Org. Chem.* **2006**,
*71*, 2009–2013. doi:10.1021/jo052370h

199. Tsai, C.-C.; Chien, C.-T.; Chang, Y.-C.; Lin, H.-C.; Yan, T.-H.
*J. Org. Chem.* **2005**, *70*, 5745–5747. doi:10.1021/jo050455c

200. Boger, D. L.; Boyce, C. W. *J. Org. Chem.* **2000**, *65*, 4088–4100.
doi:10.1021/jo000177b

201. Taber, D. F.; Neubert, T. D. *J. Org. Chem.* **2001**, *66*, 143–147.
doi:10.1021/jo001237g

202. Zhang, P.; Roundtree, I. A.; Morken, J. P. *Org. Lett.* **2012**, *14*,
1416–1419. doi:10.1021/ol3001552

203. Giannerini, M.; Fañanás-Mastral, M.; Feringa, B. L. *J. Am. Chem. Soc.*
**2012**, *134*, 4108–4111. doi:10.1021/ja300743t

204. Chaves-Pouso, A.; Álvarez-Constantino, A. M.; Fañanás-Mastral, M.
*Angew. Chem., Int. Ed.* **2022**, *61*, e202117696.
doi:10.1002/anie.202117696

205. Álvarez-Constantino, A. M.; Chaves-Pouso, A.; Fañanás-Mastral, M.
*Angew. Chem., Int. Ed.* **2024**, *63*, e202407813.
doi:10.1002/anie.202407813

206. Kobayakawa, T.; Tsuji, K.; Tamamura, H. *Bioorg. Med. Chem.* **2024**,
*110*, 117811. doi:10.1016/j.bmc.2024.117811

207. Liu, L.; Zhang-Negrerie, D.; Du, Y.; Zhao, K. *Org. Lett.* **2014**, *16*,
436–439. doi:10.1021/ol403321n

208. Dauzonne, D.; Royer, R. *Synthesis* **1987**, 1020–1022.
doi:10.1055/s-1987-28156

209. Raut, V. S.; Jean, M.; Vanthuyne, N.; Roussel, C.; Constantieux, T.;
Bressy, C.; Bugaut, X.; Bonne, D.; Rodriguez, J. *J. Am. Chem. Soc.*
**2017**, *139*, 2140–2143. doi:10.1021/jacs.6b11079

210. Bull, J. A.; Mousseau, J. J.; Charette, A. B. *Org. Lett.* **2008**, *10*,
5485–5488. doi:10.1021/ol802315k

211. Miele, M.; Castiglione, D.; Holzer, W.; Castoldi, L.; Pace, V.
*Chem. Commun.* **2025**, *61*, 1180–1183. doi:10.1039/d4cc05937a

212. Huo, L.; Li, X.; Zhao, Y.; Li, L.; Chu, L. *J. Am. Chem. Soc.* **2023**, *145*,
9876–9885. doi:10.1021/jacs.3c02748

213. Wang, Y.; Lam, H. *W. J. Org. Chem.* **2009**, *74*, 1353–1355.
doi:10.1021/jo802475x

214. Zeng, Y.-F.; Ji, W.-W.; Lv, W.-X.; Chen, Y.; Tan, D.-H.; Li, Q.;
Wang, H. *Angew. Chem., Int. Ed.* **2017**, *56*, 14707–14711.
doi:10.1002/anie.201709070

215. Zweifel, G.; Lewis, W.; On, H. P. *J. Am. Chem. Soc.* **1979**, *101*,
5101–5102. doi:10.1021/ja00511a068

216. Nelson, D. J.; Blue, C. D.; Brown, H. C. *J. Am. Chem. Soc.* **1982**, *104*,
4913–4917. doi:10.1021/ja00382a029

217. Lhermet, R.; Ahmad, M.; Hauduc, C.; Fressigné, C.; Durandetti, M.;
Maddaluno, J. *Chem. – Eur. J.* **2015**, *21*, 8105–8111.
doi:10.1002/chem.201500201

218. Bartfield, N. M.; Alexander, B. W.; Herzon, S. B. *J. Am. Chem. Soc.*
**2025**, *147*, 24921–24931. doi:10.1021/jacs.5c07148

219. Salaun, J.; Garnier, B.; Conia, J. M. *Tetrahedron* **1974**, *30*,
1413–1421. doi:10.1016/s0040-4020(01)97256-4

220. Linstrumelle, G.; Krieger, J. K.; Whiteside, G. *M. Org. Synth.* **1976**, *55*,
103–113. doi:10.15227/orgsyn.055.0103

221. Flaming, I.; Pearce, A. *J. Chem. Soc., Perkin Trans. 1* **1980**,
2485–2489. doi:10.1039/p19800002485

222. Wittig, G.; Witt, H. *Ber. Dtsch. Chem. Ges. A* **1941**, *74*, 1474–1491.
doi:10.1002/cber.19410740819

223. Schlosser, M.; Ladenberger, V. *Chem. Ber.* **1967**, *100*, 3877–3892.
doi:10.1002/cber.19671001209

224. Schlosser, M.; Ladenberger, V. *Chem. Ber.* **1967**, *100*, 3893–3900.
doi:10.1002/cber.19671001210

225. Alami, M.; Crousse, B.; Linstrumelle, G. *Tetrahedron Lett.* **1995**, *36*,
3687–3690. doi:10.1016/0040-4039(95)00612-g

226. Köbrich, G.; Flory, K. *Tetrahedron Lett.* **1964**, *5*, 1137–1142.
doi:10.1016/s0040-4039(00)90442-8

227. Cunico, R. F. *Tetrahedron Lett.* **1975**, *16*, 2935–2936.
doi:10.1016/s0040-4039(00)75035-0

228. Fischer, R. H.; Baumann, M.; Köbrich, G. *Tetrahedron Lett.* **1974**, *15*,
1207–1208. doi:10.1016/s0040-4039(01)82446-1

229. Taber, D. F.; Meagley, R. P.; Doren, D. J. *J. Org. Chem.* **1996**, *61*,
5723–5728. doi:10.1021/jo960973a

230. Marek, I. *Chem. Rev.* **2000**, *100*, 2887–2900. doi:10.1021/cr990288e

231. Knorr, R. *Chem. Rev.* **2004**, *104*, 3795–3850. doi:10.1021/cr030616h
232. Grainger, R. S.; Munro, K. R. *Tetrahedron* **2015**, *71*, 7795–7835.
doi:10.1016/j.tet.2015.06.053

233. Doucet, H. *Eur. J. Org. Chem.* **2008**, 2013–2030.
doi:10.1002/ejoc.200700984

234. Guillerm, D.; Linstrumelle, G. *Tetrahedron Lett.* **1985**, *26*, 3811–3812.
doi:10.1016/s0040-4039(00)89257-6

235. Zhai, F.; Schrock, R. R.; Hoveyda, A. H.; Müller, P. *Organometallics*
**2020**, *39*, 2486–2492. doi:10.1021/acs.organomet.0c00275

236. Liu, Q.; Mu, Y.; Koengeter, T.; Schrock, R. R.; Hoveyda, A. H.
*Nat. Chem.* **2022**, *14*, 463–473. doi:10.1038/s41557-022-00893-5

237. Alami, M.; Linstrumelle, G. *Tetrahedron Lett.* **1991**, *32*, 6109–6112.
doi:10.1016/0040-4039(91)80765-x

238. Alami, M.; Crousse, B.; Linstrumelle, G. *Tetrahedron Lett.* **1994**, *35*,
3543–3544. doi:10.1016/s0040-4039(00)73232-1

239. Ou, H.; Zhao, X.; Luo, Y. *Org. Biomol. Chem.* **2024**, *22*, 1374–1377.
doi:10.1039/d3ob01931d

240. Nishino, S.; Sudo, K.; Kurahashi, T. *Org. Lett.* **2024**, *26*, 4049–4054.
doi:10.1021/acs.orglett.4c00707

241. Payamifar, S.; Behrouzi, L.; Poursattar Marjani, A. *Arabian J. Chem.*
**2024**, *17*, 105822. doi:10.1016/j.arabjc.2024.105822

242. VanBrunt, M. P.; Ambenge, R. O.; Weinreb, S. M. *J. Org. Chem.*
**2003**, *68*, 3323–3326. doi:10.1021/jo020739m

243. Li, S.; Zhu, B.; Lee, R.; Qiao, B.; Jiang, Z. *Org. Chem. Front.* **2018**, *5*,
380–385. doi:10.1039/c7qo00798a

244. Shi, Z.-F.; Xu, L.-N.; Chen, J.; Luo, H.-X.; Zhang, J.; Cao, X.-P.
*Asian J. Org. Chem.* **2019**, *8*, 161–170. doi:10.1002/ajoc.201800575

245. Lansbury, P. T. *Acc. Chem. Res.* **1972**, *5*, 311–320.
doi:10.1021/ar50057a004

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