# Synthesis of Pentafluorosulfanylated Ynamides and Further Functionalizations

Lucas Popek, Gauthier Lefebvre, Vincent Debrauwer, David Roubaud, Nicolas

Blanchard, Christophe Meyer, Vincent Bizet

► To cite this version:

Lucas Popek, Gauthier Lefebvre, Vincent Debrauwer, David Roubaud, Nicolas Blanchard, et al. Synthesis of Pentafluorosulfanylated Ynamides and Further Functionalizations. Organic Letters, 2024, 26 (48), pp.10369-10375. 10.1021/acs.orglett.4c03972. hal-04975519

HAL Id: hal-04975519

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# Synthesis of Pentafluorosulfanylated Ynamides and Further Functionalizations

Lucas Popek, Gauthier Lefebvre, Vincent Debrauwer, David Roubaud, Nicolas Blanchard,*
Christophe Meyer,* and Vincent Bizet*

**ABSTRACT:** Herein is described the first synthesis of SF₅-ynamides, versatile building blocks featuring the pentafluorosulfanyl motif. This synthesis proceeds through a two-step sequence of radical SF₅-addition onto the π-system of a wide range of terminal ynamides and derivatives substituted with various nitrogen fragments followed by a dehydrochlorination reaction. A selection of downstream functionalization reactions, including nucleophilic additions, cycloadditions, and sulfur ylide synthesis, highlights the wide-ranging applications of this novel type of functionalized SF₅-building block.

<figure><img src="image_2.png" /></figure>

Ynamides are stable nitrogen-substituted alkynes, surrogates of labile ynamines,¹ which display a remarkable balance between stability and reactivity. The nitrogen atom induces a strong polarization of the triple bond, whereas the electron-withdrawing group (EWG) enhances the stability and can also serve as a directing group.² Various classes of ynamides and derivatives have been developed substituted with various electron-withdrawing groups to play on the stability and reactivity balance (Scheme 1a).³ Ynamides have emerged as versatile building blocks in numerous chemical transformations over the last decades, including for example radical reactions,⁴ cycloaddition reactions,⁵ heterocyclic syntheses,⁶ or metal-mediated transformations.⁷ Nowadays, numerous general methods for the synthesis of ynamides have been developed. Those methods are mostly based on the direct alkynylation of nitrogen nucleophiles by copper-catalyzed alkynylation with bromoalkynes,⁸ terminal alkynes,⁹ potassium alkynyltrifluoroborates,¹⁰ reaction with hypervalent alkynyliodonium salts,¹¹ copper-acetylides¹² or by using trichloroethylene as a two-carbon synthon.¹³ Synthesis of push-pull ynamides substituted by a fluorinated group remains rare, and a single example of CF₃-ynamide was described by the group of Perez-Luna in 2018 (Scheme 1b).¹⁴,¹⁵ This method, inspired by the practical trifluoromethylation reaction of terminal alkynes,¹⁶ is based on the oxidative copper-catalyzed direct trifluoromethylation of a terminal N-ethynyl oxazolidinone leading to the corresponding CF₃-yne-carbamate in 15% yield. Recent breakthrough in the chemistry of the pentafluorosulfanyl group (SF₅) showed that SF₅-alkynes,¹⁷ prepared from SF₅Cl,¹⁸ are versatile building blocks for heterocyclic synthesis, cycloaddition, and hydrofunctionnalization reactions. Recently, we developed an efficient way to access a silylated SF₅-alkyne,¹⁷b which remains a rare example of heterosubstituted SF₅-alkyne. Herein is reported a general and efficient method

<figure><img src="image_3.png" /><figcaption>**Scheme 1.** Main Classes of Ynamides, State of the Art about Synthesis of CF₃-ynamide, and Proposed Strategy for Synthesis of SF₅-ynamides and Further Derivatizations</figcaption></figure>
to access SF₅-ynamides through SF₅-radical addition across readily available terminal ynamides. Furthermore, we performed a selection of downstream functionalization reactions to highlight that SF₅-ynamide scaffolds are suitable platforms to access molecular diversity (Scheme 1c).

We started the study by the reaction of terminal ynamides with SF₅Cl under previously described classical pentafluorosulfanylation conditions (Scheme 2).17b,19 Unfortunately, it proved to not be very general, leading in some cases to complex mixtures. A thorough screening of reaction parameters led to a first set of conditions (Conditions A) using a monosolvent system in which the ynamide, Et₃B, and the

<figure><img src="image_4.png" /><figcaption>**Scheme 2. Substrate Scope of Chloropentafluorosulfanylation of Ynamides**</figcaption></figure>

SF₅Cl gas are dissolved and stirred at -50 °C for two hours in CH₂Cl₂. Indeed, it was found crucial to initiate the radical reaction by addition of Et₃B to a solution of SF₅Cl prior to the addition of the ynamide substrate in order to minimize products arising from undesired ionic chlorofluorination reactions (see Table S1 in the Supporting Information for details).20 This system delivers the corresponding (E)-1-chloro-2-SF₅-enamide (2a) in an encouraging 61% isolated yield. The structure and the stereoselectivity were confirmed by single-crystal X-ray diffraction analysis of compounds 2a, 2l, 2o, and 2q (CCDC 2367224, 2372003, 2372000, 2372002),21 confirming a trans addition of SF₅Cl across the triple bond.22 The internal ynamide 1b was also a competent reaction partner delivering compound 2b in 64% yield. These conditions were applied to other yne-carbamates either with a Boc (1c to 1h) or a Cbz (1i) as the electron-withdrawing group on the nitrogen atom and to yne-amide (1k) to deliver the corresponding products 2c-k in yields ranging from 57% to 71%. Unfortunately, those conditions were not applicable to all classes of ynamides, and we rapidly identified that the use of CH₂Cl₂ as solvent was detrimental in the case of ynesulfonamides (1l).

In this case, a complex mixture of the expected (E)-1-chloro-2-SF₅-enamide 2l, along with fluoro-chloro and difluoro-dichloro adducts resulting from competitive ionic reaction pathways, were obtained (see the Supporting Information for more details). Indeed, tosyl-ynamides are known to display a stronger nucleophilic character than yne-carbamates.23 To overcome this limitation, we reoptimized the reaction conditions, and to minimize the ionic reaction pathways, the polarity of the reaction medium was decreased by running the reaction in a hydrocarbon solvent (heptane or hexane). We discovered that only a minimum amount of CH₂Cl₂, or in some cases toluene, was added to completely dissolve the terminal ynamides. This solution could then be added to a -50 °C heptane or hexane solution containing condensed SF₅Cl gas immediately after initiation of the radical reaction by the addition of Et₃B (Conditions B or C). This second set of conditions achieves an optimal balance between reactivity and selectivity to deliver the desired N-Bn, N-Boc (E)-1-chloro-2-SF₅-enamide (2c) in 90% yield. Compared to conditions A, conditions B and C led to superior yields for the previously accessible N-carbamate (2f), oxazolidinone (2a), benzyloxycarbonyl (2i and 2j), and acetyl derivative (2k), delivering the corresponding products in up to 91% isolated yield. In addition, the reaction proceeds smoothly with yne-sulfonamides to deliver corresponding (E)-1-chloro-2-SF₅-enamides 2l and 2m in 90% and 78% yield, respectively. Next, we focused on terminal N-allyl yne-sulfonamide 1n, which contains two π-systems that might compete for the addition of the electrophilic pentafluorosulfanyl radical. It was observed that the addition occurs only on the electron-rich ynamide C≡C bond under the conditions used, which leads to 2n in a satisfactory 58% yield. We then extended the scope of this transformation to other classes of substrates, and the transformation proved to be compatible with vinylogous ynamide (1o), yne-hydrazide (1p), yne-urea (1q), and ynimides (1r) with the formation of the corresponding (E)-1-chloro-2-SF₅-enamides 2o, 2p, 2q, and 2r, respectively, which were obtained in moderate to good yields (50–92%). With this library of (E)-1-chloro-2-SF₅-enamides 2 in hand, we investigated the remaining dehydrochlorination step of the planned synthetic sequence toward SF₅-ynamides. The stand-

<footnote>ᵃHeptane was used instead of CH₂Cl₂. ᵇReaction was stirred at rt for 4 h instead of -50 °C for 2 h. ᶜOn 3.9 mmol scale. ᵇOn 2.8 mmol scale.
ᶜToluene was not necessary, but the reaction has to be conducted without addition of air.</footnote>
ard conditions reported by Dolbier et al. (LiOH/DMSO)¹⁹ were not optimal as they resulted in partial to complete hydrolysis of the SF₅-ynamide 3 into α-SF₅ acetamide 5. The dehydrochlorination reaction was, thus, smoothly accomplished in a straightforward manner by treatment of (E)-1-chloro-2-SF₅-enamide 2 with lithium bis(trimethylsilyl)amide (LiHMDS) in THF at 0 °C. SF₅-ynamides 3 were obtained in high yields ranging from 65% to 95% (Scheme 3). SF₅-yne-

<figure><img src="image_5.png" /><figcaption>**Scheme 3.** Substrate Scope of Formation of SF₅-ynamides through Dehydrochlorination</figcaption></figure>

**Sensitive examples**

<figure><img src="image_6.png" /></figure>

ᵃNaH (5 equiv) in DMSO was used instead of the standard conditions. ᵇAqueous workup leads to the hydrolysis into 5l and 2l and should be avoided. ᶜ¹⁹F NMR yield. ᵈYne-amide 3a generated in situ quickly reacted with LiHMDS to give the hydroamination product 6aa.

carbamates (3c–3i) were isolated in high yields, up to 95%, irrespective of the substituent of the nitrogen atom, which could be a benzylic substituent in 3c and 3d, an aromatic group in 3f, or aliphatic side chains in 3e and 3i. Similarly, enamides 2p and 2q reacted both smoothly to give the corresponding SF₅-yne-hydrazine (3p) or SF₅-yne-urea (3q) in 65% and 73% isolated yields, respectively. In a previous study, we demonstrated the *in situ* SF₅-alkyne generation using a combination of NaH in DMSO to promote the dehydrochlorination step.²⁴ This strategy is also efficient, as highlighted in the synthesis of SF₅-yne-amide 3k in 74% yield.

It should be noted that the majority of the ynamides is stable over time, as confirmed by the analysis of samples stored at +4 °C for at least 5 months without any noticeable degradation or hydrolysis. In contrast, SF₅-yne-sulfonamide 3l proved to be

significantly more sensitive. For example, an acidic workup with 1 N HCl of SF₅-yne-sulfonamide 3l yielded a mixture of α-SF₅-amide 5l and SF₅ chloro-olefin 2l. This can easily be explained by protonation of the ynamide under acidic conditions to form a highly electrophilic keteniminium intermediate 4l, which then reacts with a nucleophile—here, water or chloride anion—to deliver 5l or 2l, respectively.²² Hence, after dehydrochlorination of 2l, an aqueous workup was omitted and the SF₅-yne-sulfonamide 3l was isolated by flash chromatography in 68% yield. This compound could be used directly in solution after dehydrochloration (*vide infra*). We observed a limitation with oxazolidinone-derived substrate 2a for which the generated SF₅-ynamide intermediate 3a underwent a hydroamination reaction²⁴ upon treatment with LiHMDS. This resulted in the formation of the remarkably stable adduct 6aa²⁵ isolated in 91% (Scheme 3). This transformation consistently occurred irrespective of the amount of LiHMDS employed, and 2a was the only (E)-1-chloro-2-SF₅-enamide exhibiting this peculiar reactivity among the substrates screened.

Based on this observation, the reactivity of SF₅-ynamides was investigated in other hydroelementation reactions (Scheme 4). Several nitrogen or oxygen heteronucleophiles

<figure><img src="image_7.png" /><figcaption>**Scheme 4.** Nucleophilic Addition of *N*- and *O*-Nucleophiles to SF₅-ynamides</figcaption></figure>

ᵃReaction performed from the corresponding (E)-1-chloro-2-SF₅-enamide 2 with 5 equiv of NaH. ᵇZ/E = 89:11.

underwent efficient regio- and stereoselective additions across the triple bond of SF₅-ynamides leading to (Z)-SF₅-(hetero)-enamides 6 in good yields. The Z-stereochemistry was attributed by analogy with our previous work on the hydroamination of SF₅-alkynes and a NOESY experiment of compound 6lb.²⁴ A short selection of nucleophiles, including azide, hydrazine, or phenol derivatives, was successfully introduced on SF₅-ynamides leading to the corresponding (Z)-2-SF₅-enamide 6. In light of the difficulties previously encountered with the isolation of SF₅-yne-sulfonamides, these compounds could be generated *in situ* and reacted with a nucleophile in a one-pot strategy to give the corresponding adducts 6lb, 6mb, and 6ld in 61–67% overall yields over two
steps. This strategy is equally applicable to unstable SF₅-ynamides. For instance, the vinylogous ynamide 3o could not be observed or isolated because of its reactivity/instability. We showed it was possible to generate 3o in situ and to trap it directly with a nucleophile to generate enamide 6od in 55% yield. Overall, SF₅-ynamides showed higher reactivity than the parent SF₅-alkynes, probably because of their unique push-pull system. In our search for alternative dehydrochlorination reaction conditions (*vide supra*), we discovered that treating enamide 2 with 5 equiv of sodium hydride in DMSO did not yield the anticipated ynamide 3. Instead, it resulted in nucleophilic addition of DMSO followed by a Pummerer-like rearrangement to produce bench-stable sulfur ylide 7a in 59% isolated yield.²⁶ The structure was unambiguously confirmed by single-crystal X-ray diffraction (CCDC 2372001; Scheme 5). To the best of our knowledge, this is the first reported

Scheme 5. Sulfur Ylide Formation in the Presence of DMSO

<figure><img src="image_8.png" /></figure>

example of an SF₅-ylide. This straightforward synthesis showcases the novel reactivity of SF₅-substituted alkynes. In the solid state, the C··SMe₂ distance in 7a is 1.719 Å, which is similar to the 1.723 Å reported for the similar C=S sulfur ylide bond.²⁷ Similar findings were observed with bench-stable SF₅-yne-carbamate 3c, which yielded ylide 7c in 82% yield. The reaction occurred under mild reaction conditions just by dissolving ynamide 3c in dry DMSO and stirring the mixture at room temperature for 16 h. Further developments are needed at this stage, but it appears that SF₅ could potentially serve as a relevant group to stabilize ylides, thereby paving the way for an exciting new branch of SF₅ chemistry. We then evaluated the reactivity of SF₅-ynamide 3 in several downstream functionalization reactions (Scheme 6). As mentioned before, SF₅-ynamides react smoothly with a diversity of nitrogen- and oxygen-containing nucleophiles. In addition, it is possible to achieve their hydrolysis, as illustrated with the formation of α-SF₅-amides 5c (82%) and 5l (85%).

The sensitive N-sulfonyl-ynamide 3l was hydrolyzed at room temperature, while a higher temperature (70 °C) was required to hydrolyze the less nucleophilic yne-carbamate 3c. The synthetic methodology we developed earlier this year to access 2-SF₅-indenols was successfully extended to SF₅-ynamides and provided the corresponding 2-SF₅-3-amino-indenol 11c in acceptable 55% yield.²⁸ We also performed dibromination of SF₅-ynamide 3c to selectively give the cis-isomer 12c in 83% isolated yield by analogy with a previous work.²²c The SF₅-ynamides 3 were also involved in 1,3-dipolar cycloadditions with a nitrone 13,²⁹ a pyridinium ylide 15,³⁰ or a pyridinium amide 17 for the synthesis of isooxazolines 14c and 14l, aminoindolizine 16c, and pyrazolo[1,5-a]pyridine 18c in yields ranging from 38% to 58%.

Scheme 6. Selection of Postfunctionalization Reactions

a) Ionic and metal-catalyzed reactions

<figure><img src="image_9.png" /></figure>

b) Cycloaddition reactions

<figure><img src="image_10.png" /></figure>

<figure><img src="image_11.png" /></figure>

In conclusion, we have developed a short, efficient, and general method to access various classes of SF₅-ynamides in good yields. Leveraging a well-established synthesis of terminal ynamides, we systematically explored a diverse range of electron-withdrawing groups for these ynamides, including carbamate, amide, sulfonamide, urea, and hydrazide. The reactivity of these unique SF₅-containing building blocks was then explored though a selection of regioselective functionalizations, such as 1,3-dipolar cycloadditions, ylide formation, dibromination, and nucleophilic additions. Further transformations of sulfur ylide 7 are underway in our group and will be published in due course. A wide array of products could be obtained, thereby expanding the chemical space of SF₅-containing products. Furthermore, we illustrated that some of these transformations can also be carried out directly from the corresponding (E)-1-chloro-2-SF₅-enamides for SF₅-ynamides that cannot be isolated, thereby shortening the overall synthetic sequence by one step.

<figure><img src="image_12.png" /></figure>

ASSOCIATED CONTENT

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

<figure><img src="image_13.png" /></figure>

**Supporting Information**

The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.4c03972.

Preparation of terminal ynamides, preparation of SF₅-
ynamides, and copies of NMR spectra (PDF)
## Accession Codes

Deposition Numbers 2367224 and 2372000–2372003 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via the joint Cambridge Crystallographic Data Centre (CCDC) and Fachinformationszentrum Karlsruhe Access Structures service.

## ■ AUTHOR INFORMATION

### Corresponding Authors

Nicolas Blanchard – Université de Haute-Alsace, Université de Strasbourg, CNRS, LIMA, UMR 7042, 68000 Mulhouse, France; ● orcid.org/0000-0002-3097-0548; Email: n.blanchard@unistra.fr

Christophe Meyer – Molecular, Macromolecular Chemistry, and Materials, ESPCI Paris-PSL, CNRS, 75005 Paris, France; ● orcid.org/0000-0003-3420-5584; Email: christophe.meyer@espci.fr

Vincent Bizet – Université de Haute-Alsace, Université de Strasbourg, CNRS, LIMA, UMR 7042, 68000 Mulhouse, France; ● orcid.org/0000-0002-0870-1747; Email: vbizet@unistra.fr

### Authors

Lucas Popek – Université de Haute-Alsace, Université de Strasbourg, CNRS, LIMA, UMR 7042, 68000 Mulhouse, France; ● orcid.org/0000-0002-8894-1467

Gauthier Lefebvre – Molecular, Macromolecular Chemistry, and Materials, ESPCI Paris-PSL, CNRS, 75005 Paris, France

Vincent Debrauwer – Université de Haute-Alsace, Université de Strasbourg, CNRS, LIMA, UMR 7042, 68000 Mulhouse, France

David Roubaud – Molecular, Macromolecular Chemistry, and Materials, ESPCI Paris-PSL, CNRS, 75005 Paris, France

Complete contact information is available at: https://pubs.acs.org/10.1021/acs.orglett.4c03972

## Notes

The authors declare no competing financial interest.

## ■ ACKNOWLEDGMENTS

This work was supported by ANR DEFIS project (grant ANR-PRC-17-CE07-0008) and ANR SULFIVE project (grant ANR-PRC-21-CE07-0042) of the French National Research Agency (ANR). The authors acknowledge Didier Le Nouën (LIMA UMR7042 CNRS-Unistra-UHA) and Corinne Bailly and Nathalie Gruber (Service de radiocrystallographie de la Fédération de Chimie Le Bel FR 2010) who contributed, by their valuable technical and scientific support in NMR and X-ray diffraction, to the achievement of this research project. The authors also acknowledge MS3U of Sorbonne Université for HRMS analysis and Geoffrey Gontard (IPCM) for X-ray crystallographic analysis.

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(14) de la Vega-Hernández, K.; Romain, E.; Coffinet, A.; Bijouard, K.; Gontard, G.; Chemla, F.; Ferreira, F.; Jackowski, O.; Perez-Luna, A. Radical Germylzincation of α-Heteroatom-Substituted Alkynes. *J. Am. Chem. Soc.* **2018**, *140*, 17632–17642.

(15) CF₃-ynamines have been prepared by elimination reactions applied to 2,2,3,3,3-pentafluoropropyl amines; see: (a) Yamanaka, H.; Mantani, T.; Shiomi, K.; Ishihara, T. A New Practical and Convenient Access to the Synthesis of N,N-Dialkyl-3,3,3-trifluoropropanamides. *Chem. Lett.* **1998**, *27*, 615–616. (b) Mantani, T.; Shiomi, K.; Konno, T.; Ishihara, T.; Yamanaka, H. A Convenient Preparation of 3,3,3-Trifluoro-1-propynylamines and Their Lewis Acid Catalyzed Reaction with Carbonyl Compounds Leading to (Z)-α-(Trifluoromethyl)-α,β-unsaturated Amides. *J. Org. Chem.* **2001**, *66*, 3442–3448. (c) Ishihara, T.; Mantani, T.; Konno, T.; Yamanaka, H. Preparation of trifluoromethylated ynamines and their reactions with some electrophilic reagents. *Tetrahedron* **2006**, *62*, 3783–3793.

(16) (a) Chu, L.; Qing, F.-L. Copper-Mediated Aerobic Oxidative Trifluoromethylation of Terminal Alkynes with Me₃SiCF₃. *J. Am. Chem. Soc.* **2010**, *132*, 7262–7263. (b) Tresse, C.; Guissart, C.; Schweizer, S.; Bouhoute, Y.; Chany, A.-C.; Goddard, M.-L.; Blanchard, N.; Evano, G. Practical Methods for the Synthesis of Trifluoromethylated Alkynes: Oxidative Trifluoromethylation of Copper Acetylides and Alkynes. *Adv. Synth. Catal.* **2014**, *356*, 2051–2060.

(17) For SF₅-alkynes, see: (a) Popek, L.; Nguyen, T. M.; Blanchard, N.; Cahard, D.; Bizet, V. Synthesis and further use of SF₅-alkynes as platforms for the design of more complex SF₅-containing products. *Tetrahedron* **2022**, *117–118*, 132814. (b) Nguyen, T. M.; Popek, L.; Matchavariani, D.; Blanchard, N.; Bizet, V.; Cahard, D. Expanding Radical Chloropentafluorosulfanylation of Alkynes. *Org. Lett.* **2024**, *26*, 365–369. (c) Abd El Sater, M.; Popek, L.; Blanchard, N.; Bizet, V. Recent advances in the chemistry and the application of SF₅-compounds. *Synthesis* **2024**. (d) Rene, F.; Clément-Comoy, L.; Blanchard, N.; Bizet, V. Recent achievements in the synthesis and reactivity of pentafluorosulfanyl-alkynes. *C. R. Chim.* **2024**, *27*, 227–240.

(18) Selected examples of direct introduction of SF₅: (a) Wang, L.; Qin, W. Copper-Initiated Regiodivergent Chloropentafluorosulfanylation of 1,3-Enynes under Substrate Control. *Org. Lett.* **2024**, *26*, 5049–5054. (b) Kraemer, Y.; Buldt, J. A.; Kong, W.-Y.; Stephens, A. M.; Ragan, A. N.; Park, S.; Haidar, Z. C.; Patel, A. H.; Shey, R.; Dagan, R.; McLoughlin, C. P.; Fettinger, J. C.; Tantillo, D. J.; Pitts, C. R. Overcoming a Radical Polarity Mismatch in Strain-Release Pentafluorosulfanylation of [1.1.0]Bicyclobutanes: An Entryway to Sulfone- and Carbonyl-Containing SF₅-Cyclobutanes. *Angew. Chem., Int. Ed.* **2024**, *63*, No. e202319930. (c) Nguyen, T. M.; Legault, C. Y.; Blanchard, N.; Bizet, V.; Cahard, D. Tracking SF₅I in the Iodopentafluorosulfanylation of Alkynes. *Chem.—Eur. J.* **2023**, *29*, No. e202302914. (d) Kordnezhadian, R.; De Bels, T.; Su, K.; Van Meervelt, L.; Ismalaj, E.; Demaerel, J.; De Borggraeve, W. M. An Extrusion Strategy for On-Demand SF₅Cl Gas Generation from a Commercial Disulfide. *Org. Lett.* **2023**, *25*, 8947–8951. (e) Zhao, X.; Shou, J.-Y.; Qing, F.-L. Iodopentafluorosulfanylation of [1.1.1]-propellane and further functionalizations. *Sci. China Chem.* **2023**, *66*, 2871–2877. (f) Ouellet-Du Berger, M.-R.; Boucher, M.; Paquin, J.-F. Light-activation of SF₅Cl for the atom transfer radical addition onto alkenes and alkynes. *J. Fluorine Chem.* **2023**, *268*, 110131.

(g) Taponard, A.; Jarrosson, T.; Khrouz, L.; Médebielle, M.; Broggi, J.; Tlili, A. Metal-Free SF₆ Activation: A New SF₅-Based Reagent Enables Deoxyfluorination and Pentafluorosulfanylation Reactions. *Angew. Chem., Int. Ed.* **2022**, *61*, No. e202204623. (h) Shou, J.-Y.; Xu, X.-H.; Qing, F.-L. The radical reaction of ethynylbenziodoxolone (EBX) reagents with pentafluorosulfanyl chloride: New approach to SF₅-substituted alkynes. *J. Fluorine Chem.* **2022**, *261–262*, 110018.

(i) Shou, J.-Y.; Qing, F.-L. Three-Component Reaction of Pentafluorosulfanyl Chloride, Alkenes and Diazo Compounds and Synthesis of Pentafluorosulfanylfurans. *Angew. Chem., Int. Ed.* **2022**, *61*, No. e202208860. (j) Birepinte, M.; Champagne, P. A.; Paquin, J.-F. Photoinitiated anti-Hydropentafluorosulfanylation of Terminal Alkynes. *Angew. Chem., Int. Ed.* **2022**, *61*, No. e202112575. (k) Gilbert, A.; Birepinte, M.; Paquin, J.-F. Electron donor-acceptor (EDA)-complex enabled SF₅Cl addition on alkenes and alkynes. *J. Fluorine Chem.* **2021**, *243*, 109734. (l) Gilbert, A.; Langowski, P.; Delgado, M.; Chabaud, L.; Pucheault, M.; Paquin, J.-F. Amine-borane complex-initiated SF₅Cl radical addition on alkenes and alkynes. *Beilstein J. Org. Chem.* **2020**, *16*, 3069–3077.

(19) Dolbier, W. R.; Ait-Mohand, S.; Schertz, T. D.; Sergeeva, T. A.; Cradlebaugh, J. A.; Mitani, A.; Gard, G. L.; Winter, R. W.; Thrasher, J. S. A convenient and efficient method for incorporation of pentafluorosulfanyl (SF₅) substituents into aliphatic compounds. *J. Fluorine Chem.* **2006**, *127*, 1302–1310.

(20) A similar observation was made in the case of addition of SF₃Br to enol acetates; see: Ngo, S. C.; Lin, J.-H.; Savoie, P. R.; Hines, E. M.; Pugliese, K. M.; Welch, J. T. Preparation and Reactions of Aliphatic 2-Pentafluorosulfanyl Aldehydes. *Eur. J. Org. Chem.* **2012**, *2012*, 4902–4905.

(21) (a) X-ray diffraction presented using *CYLview20*; Legault, C. Y., Ed.; Université de Sherbrooke, 2020. http://www.cylview.org.

(22) (a) Debrauwer, V.; Leito, I.; Lõkov, M.; Tshepelevitsh, S.; Parmentier, M.; Blanchard, N.; Bizet, V. Synthesis and Physicochemical Properties of 2-SF₅-(Aza)Indoles, a New Family of SF₅ Heterocycles. ACS Org. Inorg. Au **2021**, *1*, 43–50. (b) Gilbert, A.; Langowski, P.; Delgado, M.; Chabaud, L.; Pucheault, M.; Paquin, J.-F. Correction: Amine-borane complex-initiated SF₅Cl radical addition on alkenes and alkynes. *Beilstein J. Org. Chem.* **2021**, *17*, 1725–1726. (c) Matchavariani, D.; Popek, L.; Cabrera-Trujillo, J. J.; Nguyen, T. M.; Blanchard, N.; Miqueu, K.; Cahard, D.; Bizet, V. Ambiphilic Reactivity of SF₅-Alkynes Applied to Regioselective and Stereo-divergent Halogenation Reactions: An Experimental and Theoretical Case Study. *Adv. Synth. Catal.* **2024**, *366*, 3481–3493.

(23) Laub, H. A.; Evano, G.; Mayr, H. Hydrocarvation of C≡C Bonds: Quantification of the Nucleophilic Reactivity of Ynamides. *Angew. Chem., Int. Ed.* **2014**, *53*, 4968–4971.

(24) Popek, L.; Cabrera-Trujillo, J. J.; Debrauwer, V.; Blanchard, N.; Miqueu, K.; Bizet, V. Regio- and Stereoselective Hydroelementation
of SF₅-Alkynes and Further Functionalizations. *Angew. Chem., Int. Ed.* **2023**, *62*, No. e202300685.

(25) For a previous example of base-catalyzed hydroamination of a N-alkynyl oxazolidinone, see: Dooleweerdt, K.; Birkedal, H.; Ruhland, T.; Skrydstrup, T. Irregularities in the Effect of Potassium Phosphate in Ynamide Synthesis. *J. Org. Chem.* **2008**, *73*, 9447–9450.

(26) For review on S(IV) bond-forming and -breaking reactions, see: Kaiser, D.; Klose, I.; Oost, R.; Neuhaus, J.; Maulide, N. Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts. *Chem. Rev.* **2019**, *119*, 8701–8780.

(27) Klimczyk, S.; Huang, X.; Kählig, H.; Veiros, L. F.; Maulide, N. Stereoselective Gold(I) Domino Catalysis of Allylic Isomerization and Olefin Cyclopropanation: Mechanistic Studies. *J. Org. Chem.* **2015**, *80*, 5719–5729.

(28) Popek, L.; Cihan, M.; Blanchard, N.; Bizet, V. Palladium-Catalyzed Regioselective Synthesis of 2-SF₅-Indenols and Further Derivatizations. *Angew. Chem., Int. Ed.* **2024**, *63*, No. e202315909.

(29) For a previous example with SF₅-alkynes, see: Lopez, S. E.; Mitani, A.; Pena, P.; Ghiviriga, I.; Dolbier, W. R. Use of 1-pentafluorosulfanyl-phenylacetylenes for the preparation of SF₅-substituted five-membered ring heterocycles through 1,3-dipolar cycloadditions. *Isoxazoles and isoxazolines*. *J. Fluorine Chem.* **2015**, *176*, 121–126.

(30) Brioche, J.; Meyer, C.; Cossy, J. Synthesis of 2-Aminodolizines by 1,3-Dipolar Cycloaddition of Pyridinium Ylides with Electron-Deficient Ynamides. *Org. Lett.* **2015**, *17*, 2800–2803.