# Ene-yne cross-metathesis for the preparation of
2,3-diaryl-1,3-dienes

M.K. Abderrezak, Z. Kabouche, Christian Bruneau, Cedric Fischmeister

► To cite this version:

M.K. Abderrezak, Z. Kabouche, Christian Bruneau, Cedric Fischmeister. Ene-yne cross-metathesis for the preparation of 2,3-diaryl-1,3-dienes. Catalysts, 2017, 7 (12), pp.365. 10.3390/catal7120365. hal-01671635

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Article

# Ene-yne Cross-Metathesis for the Preparation of 2,3-Diaryl-1,3-dienes

Meriem K. Abderrezak<sup>1,2</sup>, Zahia Kabouche<sup>1</sup>, Christian Bruneau<sup>2,*</sup> and Cédric Fischmeister<sup>2,* ID</sup>

Received: 10 November 2017; Accepted: 21 November 2017; Published: 27 November 2017

**Abstract:** Ene-yne cross-metathesis from alkynes and ethylene is a useful method to produce substituted conjugated butadiene derivatives. If this method has been used with aliphatic alkynes, it has however never been used starting from diarylacetylenes as internal alkynes. We show that the ene-yne cross-metathesis catalyzed by the second generation Hoveyda ruthenium catalyst provides the 2,3-diarylbuta-1,3-dienes under 3 atm of ethylene at 100 °C. The scope and limitations of the reaction have been evaluated starting from unsymmetrical functionalized diarylacetylene derivatives hence leading to unsymmetrical 2,3-diarylbuta-1,3-dienes in a straightforward and environmentally acceptable manner.

**Keywords:** 1,3-dienes; ene-yne metathesis; ruthenium catalysis

## 1. Introduction

Depending on the substitution pattern of the 1,3-diene motif, different families of products in terms of electron delocalization are available. 2,3-Diarylbuta-1,3-dienes A consisting of branched π-electron frameworks are cross-conjugated compounds related to (4)-dendralenes featuring two terminal double bonds (Figure 1) [1], whereas 1,3-butadienes that are di-substituted in 1,4-position by aryl groups lead to highly conjugated compounds B with alternating single and double bonds. The 1,1-, 1,2-, and 1,3-diphenylbuta-1,3-dienes (C-E) present at the same time three conjugated double bonds and a cross-conjugated (3)-dendralene structure. Because of their conjugated 1,3-diene structure, these products are perfect starting substrates for the construction of complex molecules [2–4]. Besides the classical [4 + 2] cycloadditions, 1,3-butadiene itself and aliphatic 1,3-butadiene substrates have been efficiently transformed via transition metal-catalyzed reactions. Among them, ruthenium-catalyzed addition of aldehydes [5] and olefin metathesis [6], nickel-catalyzed multicomponent coupling with alkynes or aldehydes and dimethylzinc in the presence of carbon dioxide [7,8], rhodium-catalyzed asymmetric [4 + 3] cycloaddition with vinylcarbenoids [9], palladium-catalyzed telomerization with various nucleophiles [10–12], hydroamination [13,14] and hydroamidocarbonylation [15], are representative examples. However, monoarylated 1,3-dienes have been used for triflic acid-catalyzed synthesis of indenes [16], ruthenium-catalyzed isomerization [17], palladium-catalyzed hydroarylation with boronic esters [18], cobalt-catalyzed hydrosilylation [19], asymmetric hydrovinylation with ethylene [20] and enantioselective cycloaddition with internal alkynes [21]. 2-Aryl- and 2,3-diaryl-dienes of type A have been extensively studied for the access to cyclic products resulting from Diels–Alder [4,22]

<footnote n="1">¹ Laboratory of Therapeutic Substances Obtention (LOST), Department of Chemistry, Université Frères Mentouri Constantine, Chaabet Ersas Campus, Constantine 25000, Algeria; abderrezakmk@gmail.com (M.K.A.); zahiakabouche@gmail.com (Z.K.)</footnote>

<footnote n="2">² UMR6226 CNRS, Institut des Sciences Chimiques de Rennes, Université de Rennes 1, Organometallics: Materials and Catalysis, Centre for Catalysis and Green Chemistry, Campus de Beaulieu, 35042 Rennes CEDEX, France</footnote>

<footnote>* Correspondence: christian.bruneau@univ-rennes1.fr (C.B.); cedric.fischmeister@univ-rennes1.fr (C.F.); Tel.: +33-2-23-23-62-83 (C.B.); +33-2-23-23-59-98 (C.F.)</footnote>
and hetero-Diels–Alder reactions [23,24]. They have also been recently involved in iridium-catalyzed hydrohydroxymethylation [25] and ruthenium-catalyzed hydroxymethylation [26].

<figure><img src="image_2.png" /><figcaption>**Figure 1.** Different types of disubstituted 1,3-butadienes.</figcaption></figure>

Elimination reactions such as the thermal decomposition of 3,4-diaryldihydrothiophene-1,1-dioxides [27] and the acid-catalyzed dehydration of 1,2-diol derivatives [28] have been used for the synthesis of 2,3-diaryl-buta-1,3-dienes of type A. But-2-yn-1,4-diol biscarbonates have been efficiently coupled with aryl and heteroaryl boronic acids in the presence of a palladium catalyst to give 2,3-diarylated 1,3-dienes [1,29,30]. 1,4-Dimethoxybut-2-yne was also found to be an excellent substrate for the copper(I)-catalyzed SN2'substitution with aryl Grignard reagents to produce symmetrical 2,3-diaryllbuta-1,3-dienes [31]. Symmetrical 2,3-diaryl-1,3-dienes A have also been obtained by homocoupling methods starting directly from ketones or the corresponding hydrazones. These homocoupling reactions have been performed directly from acetophenone substrates upon treatment with SmI₂/Ac₂O [32], or from the derived hydrazones following a copper-mediated Shapiro reaction [33] or palladium-catalyzed coupling under oxidative conditions [34,35]. The preparation of 2,3-diaryllbuta-1,3-diene derivatives has been achieved by homocoupling of styrylmagnesium bromide in the presence of an organocatalyst [36], styryl bromide catalyzed by Pd/C in the presence of indium [37], and styrylboronic acid catalyzed by a palladium(II) complex in the presence of KMnO₄ or oxygen as oxidant [38]. The same symmetrical 1,3-dienes can be obtained by palladium-catalyzed cross-coupling of 2,3-bis.pinacolatoboryl)buta-1,3-diene with aryl iodides under basic conditions [39]. It is noteworthy that the preparation of unsymmetrical 2,3-diaryllbuta-1,3-dienes with different aryl groups, is much less documented. The few reported methods rely on palladium-catalyzed cross-coupling of *p*-tolyl iodide with 3-silyl-3-phenylbuta-1,3-diene in 40% yield [39] and styryl triflates with styryl boronates [40]. An unsymmetrical 2,3-bis(2-nitrophenyl)-1,3-butadiene derivative has been prepared in 61% yield by a Pd-catalyzed Stille cross-coupling [41], whereas the tentative cross-coupling of two different hydrazones led to modest yields in the unsymmetrical product besides the symmetrical ones [16]. Because it is a straightforward atom economic reaction, ene-yne cross metathesis has been applied as an efficient method for the construction of 1,3-dienes [4,42–45]. Using ethylene as olefinic substrate allows the production of buta-1,3-dienes with two terminal methylene groups according to a catalytic cycle initially proposed by M. Mori [46] and further studied in more details by S. T. Diver [47,48]. However, if many examples involving ruthenium-catalysis have been
described starting from aliphatic including benzylic and propargylic alkynes [49–52], much less data are available from aromatic alkynes in the literature. A few mono-substituted 2-arylbuta-1,3-dienes have been obtained from terminal arylacetylenes [25,26,53–56], but to the best of our knowledge only one example of synthesis of 2,3-diphenylbuta-1,3-diene via ene-yne cross-metathesis starting from an internal alkyne has been reported [57].

Herein, we report on the application of ruthenium-catalyzed ene-yne cross-metathesis for the direct preparation of 2,3-diarylbuta-1,3-dienes of type A from ethylene and a variety of internal alkynes. We focused on a new preparation of unsymmetrical dienes performed in one step with atom economy from suitably designed internal alkynes. This process competes in terms of productivity and environmental impact with the methods based on palladium-catalyzed cross-coupling of functionalized alkenes that produce the desired products in moderate yields together with stoichiometric amount of wastes [39,41].

## 2. Results and Discussion

The feasibility of the ene-yne cross-metathesis between 1,2-diphenylacetylene with ethylene was first evaluated in the presence of the second generation Grubbs (I) and Hoveyda (II) ruthenium catalysts (Figure 2, Scheme 1).

<figure><img src="image_3.png" /><figcaption>**Figure 2.** Ruthenium catalysts used in the screening experiments.</figcaption></figure>

<figure><img src="image_4.png" /><figcaption>**Scheme 1.** Ene-yne cross-metathesis of 1,2-diphenylacetylene with ethylene.</figcaption></figure>

The first attempts carried out with 1 atm of ethylene in the presence of 2 mol% of Grubbs catalyst I at room temperature in dimethyl carbonate (DMC) or dichloromethane (DCM) were not successful (Table 1, entries 1–3). Increasing the ethylene pressure to 5 atm and the temperature to 80 °C in DMC or 100 °C in toluene made the ene-yne cross-metathesis possible but with modest conversion (Table 1, entries 4 and 5). Further increase of reaction pressure and reaction time in DMC led to 90% conversion of the alkyne (Table 1, entry 6). A similar beneficial effect of increasing ethylene pressure from 1 to 6 atm had been observed during the ene-yne cross-metathesis of ethylene with terminal propargylic acetates [47]. These results indicated that the ene-yne metathesis of 1,2-diphenylacetylene required higher pressure than the ene-yne metathesis of the terminal phenylacetylene, which was carried out in short reaction time under 1 atm of C₂H₄ at 80 °C in toluene with catalyst I [26,53–55], and even at room temperature with a bimetallic ruthenium metathesis
catalyst precursor [56]. The Hoveyda catalyst II was then evaluated under various experimental conditions. In dimethyl carbonate, the conversion of **1a** at 80 °C under 5 atm of C₂H₄ was similar to that obtained with catalyst I under related conditions (Table 1, entries 4 and 7). It was possible to improve the conversion of the alkyne by increasing the initial concentration of the substrate from 0.06 M to 0.3 M (Table 1, entries 8–10). It must be noted that in all the experiments performed in DMC solvent, the formation of 1,2-diphenylbuta-1,3-diene **2a'** resulting from hydrovinylation of the alkyne by ethylene was observed as a byproduct in variable amounts. This side reaction might be attributed to the formation of Ru–H species resulting from the reaction of ruthenium species with MeOH arising from DMC decomposition. It is interesting to note that the formation of **2a'** has been reported only once by reaction of alkynes with ethylene and that a ruthenium hydride was assumed to be essential for this catalytic reaction [58]. Such Ru–H species were also previously proposed to be responsible of carbon–carbon double bonds migration during olefin metathesis reactions performed in boiling DMC [59]. Toluene appeared to be a better solvent as the reaction carried out under 3 atm of ethylene at 100 °C for 17 h gave full conversion of the alkyne (Table 1, entry 11). Not only the conversion of the alkyne was better, but the selectivity in favor of the 2,3-diphenylbuta-1,3-diene was excellent since **2a'** could not be detected. Optimization of the reaction in toluene revealed that 100 °C, 17 h were the optimum experimental conditions whereas a higher pressure of ethylene had a negative effect inhibiting the catalytic reaction, and lower catalyst loading led to decreased activity (Table 1, entries 12–15). The first generation catalyst III utilized in the conditions of entry 7 led to only 10% conversion [60] and a high proportion of hydrovinylation product **2a'**. The conditions reported in entry 11 appeared to be the best to investigate the scope of the reaction focused on the synthesis of unsymmetrical 2,3-diarylbuta-1,3-dienes.

<table><caption>**Table 1.** Optimization of the ene-yne cross-metathesis of 1,2-diphenylacetylene with ethylene <sup>a</sup>.</caption><thead><tr><th>Entry</th><th>Catalyst (mol%)</th><th>Ethylene Pressure (atm)</th><th>Solvent</th><th>T (°C)</th><th>t (h)</th><th>Conversion <sup>c</sup> (%)</th></tr></thead><tbody><tr><td>1</td><td>I (2 mol%)</td><td>1</td><td>DMC 0.01 M</td><td>25</td><td>4</td><td>0</td></tr><tr><td>2</td><td>I (2 mol%)</td><td>1</td><td>DCM 0.06 M</td><td>25</td><td>4</td><td>0</td></tr><tr><td>3</td><td>I (2 mol%)</td><td>1</td><td>DMC 0.06 M</td><td>25</td><td>4</td><td>5</td></tr><tr><td>4</td><td>I (2 mol%)</td><td>5</td><td>DMC 0.06 M</td><td>80</td><td>17</td><td>60 <sup>d</sup></td></tr><tr><td>5</td><td>I (2 mol%)</td><td>5</td><td>toluene 0.06 M</td><td>100</td><td>17</td><td>64 <sup>d</sup></td></tr><tr><td>6</td><td>I (2 mol%)</td><td>7</td><td>DMC 0.06 M</td><td>80</td><td>22</td><td>90 <sup>d</sup></td></tr><tr><td>7</td><td>II (2 mol%)</td><td>5</td><td>DMC 0.06 M</td><td>80</td><td>24</td><td>50 <sup>d</sup></td></tr><tr><td>8</td><td>II (2 mol%)</td><td>5</td><td>DMC 0.1 M</td><td>80</td><td>23</td><td>94 <sup>d</sup></td></tr><tr><td>9</td><td>II (2 mol%)</td><td>5</td><td>DMC 0.3 M</td><td>90 <sup>b</sup></td><td>17</td><td>92 <sup>d</sup></td></tr><tr><td>10</td><td>II (2 mol%)</td><td>3</td><td>DMC 0.3 M</td><td>90 <sup>b</sup></td><td>17</td><td>95 <sup>d</sup></td></tr><tr><td>11</td><td>II (2 mol%)</td><td>3</td><td>toluene 0.3 M</td><td>100</td><td>17</td><td>100 (90%) <sup>e</sup></td></tr><tr><td>12</td><td>II (2 mol%)</td><td>3</td><td>toluene 0.3 M</td><td>70</td><td>17</td><td>67</td></tr><tr><td>13</td><td>II (2 mol%)</td><td>3</td><td>toluene 0.3 M</td><td>120</td><td>8</td><td>90</td></tr><tr><td>14</td><td>II (2 mol%)</td><td>25</td><td>toluene 0.3 M</td><td>100</td><td>72</td><td>0</td></tr><tr><td>15</td><td>II (1 mol%)</td><td>3</td><td>toluene 0.3 M</td><td>100</td><td>17</td><td>80</td></tr></tbody></table>

The unsymmetrical phenylacetylene derivatives **1b–s** were prepared according to the Sonogashira method from phenylacetylene and the desired substituted halogenated aryl derivatives in the presence of catalytic amounts of PdCl₂(PPh₃)₂ and CuI (See Supplementary Materials). Several alkynes presenting different electronic and steric properties were prepared in order to evaluate the full potential of the synthetic method. The results of the ene-yne cross-metathesis reactions of these substrates with C₂H₄ (Scheme 2) are gathered in Table 2.

<footnote><sup>a</sup> Tolane (0.51 mmoles); <sup>b</sup> DMC boiling point under atmospheric pressure; <sup>c</sup> Determined by gas chromatography using tetradecane as internal standard; <sup>d</sup> presence of 1,2-diphenylbuta-1,3-diene **2a'** (up to 15% determined by <sup>1</sup>H Nuclear Magnetic Resonance); <sup>e</sup> (isolated yield).</footnote>
<figure><img src="image_5.png" /><figcaption>**Scheme 2.** Ene-yne cross-metathesis of unsymmetrical diarylacetylenes.</figcaption></figure>

The presence of an electron-donating or -withdrawing groups in *para*-position of one of the aryl groups did not inhibit the cross-metathesis with ethylene and the corresponding dienes **2b–h** were isolated in high yields after 17–24 h (Table 2, entries 1–7). Total conversion of the *para*-halogenated derivatives **1i–k** were obtained under similar conditions and the dienes **2i–k** were isolated in 89–90% yield without noticeable dehalogenation. Compounds **2i** and **2k** are particularly interesting for further cross-coupling reactions. The mixed phenyl 2-thiophenyl butadiene **2l** was isolated in 60% yield after complete conversion of the starting alkyne **1l** (Table 2, entry 11). Substitution at the *ortho*-position of one phenyl group was more problematic. Indeed, with the *o*-cyano group in **1m** a very low yield of 18% was obtained whereas no reaction took place with the *o*-OMe and *o*-NO₂ substrates **1n,o** (Table 2, entries 13 and 14) even when extended reaction time or higher temperatures were used. Both the steric hindrance and the potential catalyst inhibition by coordination of these *o*-substituents to the metal center might be at the origin of the low reactivity. Limitations were also observed with **1q–s** for which steric hindrance (1q) or substrate additional coordination site (1r,s) might be responsible from the lack of reactivity. On the contrary, the arylalkylacetylene hex-1-yn-1-ylbenzene **1p** led to full conversion and an excellent 97% isolated yield of **2p**, a class of 1,3-dienes scarcely reported employing olefin metathesis [57].

<table><caption>**Table 2.** Ene-yne cross-metathesis of unsymmetrical diarylacetylenes with ethylene <sup>a</sup>.</caption><thead><tr><th>Entry</th><th>Substrate</th><th>t (h)</th><th>Conversion (%)<sup>b</sup></th><th>Product</th><th>Yield (%)<sup>c</sup></th></tr></thead><tbody><tr><td>1</td><td><img src="image_0_0_1.png" alt="Chemical structure of 1b"></td><td>24</td><td>100</td><td><img src="image_0_0_2.png" alt="Chemical structure of 2b"></td><td>91</td></tr><tr><td>2</td><td><img src="image_0_0_3.png" alt="Chemical structure of 1c"></td><td>17</td><td>100</td><td><img src="image_0_0_4.png" alt="Chemical structure of 2c"></td><td>98</td></tr><tr><td>3</td><td><img src="image_0_0_5.png" alt="Chemical structure of 1d"></td><td>17</td><td>100</td><td><img src="image_0_0_6.png" alt="Chemical structure of 2d"></td><td>99</td></tr><tr><td>4</td><td><img src="image_0_0_7.png" alt="Chemical structure of 1e"></td><td>17</td><td>100</td><td><img src="image_0_0_8.png" alt="Chemical structure of 2e"></td><td>91</td></tr><tr><td>5</td><td><img src="image_0_0_9.png" alt="Chemical structure of 1f"></td><td>17</td><td>100</td><td><img src="image_0_0_10.png" alt="Chemical structure of 2f"></td><td>99</td></tr><tr><td>6</td><td><img src="image_0_0_11.png" alt="Chemical structure of 1g"></td><td>24</td><td>100</td><td><img src="image_0_0_12.png" alt="Chemical structure of 2g"></td><td>97</td></tr></tbody></table>
a variety of substituents on the other aryl group, except in the case of bulky aromatic substituents and substitution at the *ortho*-position.

**Supplementary Materials:** The following are available online at www.mdpi.com/2073-4344/7/12/365/s1,
(1) General information, (2) Alkyne syntheses, (3) 2,3-diarylbutadiene syntheses.

**Author Contributions:** C.B. and C.F. conceived and designed the experiments and wrote the paper; M.K.A. performed the experimental work and analyzed the analytical data. Z.K. supervised the work at the Université Frères Mentouri Constantine (Algeria).

**Conflicts of Interest:** The authors declare no conflict of interest.

**References and Notes**

1. Hayashi, S.; Kasuya, M.; Machida, J.; Koizumi, T. From propargylic biscarbonate to diaryl[n]dendralenes. *Tetrahedron Lett.* **2017**, *58*, 2429–2432. [CrossRef]

2. Hopf, H.; Sherburn, M.S. Dendralenes branch out: Cross-conjugated oligoenes allow for rapid generation of molecular complexity. *Angew. Chem. Int. Ed.* **2012**, *51*, 2298–2338. [CrossRef] [PubMed]

3. Sherburn, M.S. Preparation and synthetic value of n-bond rich branched hydrocarbons. *Acc. Chem. Res.* **2015**, *48*, 1961–1970. [CrossRef] [PubMed]

4. Kotha, S.; Meshram, M.; Tiwari, A. Advanced approach to polycyclics by a synergetic combination of enyne metathesis and Diels-Alder reaction. *Chem. Soc. Rev.* **2009**, *38*, 2065–2092. [CrossRef] [PubMed]

5. Omura, S.; Fukuyama, T.; Horiguchi, J.; Murakami, Y.; Ryu, I. Ruthenium hydride-catalyzed addition of aldehydes to dienes leading to β,γ-unsaturated ketones. *J. Am. Chem. Soc.* **2008**, *130*, 14094–14095. [CrossRef] [PubMed]

6. Balla, A.; Al-Hashimi, M.; Hlil, A.; Bazzi, H.; Tuba, R. Ruthenium-catalyzed metathesis of conjugated polyenes. *ChemCatChem* **2016**, *8*, 2865–2875. [CrossRef]

7. Mori, Y.; Mori, T.; Onodera, G.; Kimura, M. Nickel-catalyzed multicomponent coupling of alkyne, buta-1,3-diene, and dimethylzinc under carbon dioxide. *Synthesis* **2014**, *46*, 2287–2292. [CrossRef]

8. Takimoto, M.; Kajima, Y.; Sato, Y.; Mori, M. Nickel-catalyzed enantioselective three-component coupling of bis-1,3-dienes, aldehydes, and dimethylzinc. *J. Org. Chem.* **2005**, *70*, 8605–8608. [CrossRef] [PubMed]

9. Schwartz, B.D.; Denton, J.R.; Lian, Y.; Davies, H.M.L.; Williams, C.M. Asymmetric [4 + 3] cycloaddition between vinylcarbenoids and dienes: Application to the total synthesis of the natural product (6)-5-*epi*-vibsanin E. *J. Am. Chem. Soc.* **2009**, *131*, 8329–8332. [CrossRef] [PubMed]

10. Torrente-Murciano, L.; Lapkin, A.; Nielsen, D.J.; Fallis, I.; Cavell, K.J. Telomerisation of long-chain dienes with alcohols using Pd(IMes)(dvds) catalyst. *Green Chem.* **2010**, *12*, 866–869. [CrossRef]

11. Behr, A.; Becker, M.; Beckmann, T.; Johnen, L.; Leschinski, J.; Reyer, S. Telomerization: Advances and applications of a versatile reaction. *Angew. Chem. Int. Ed.* **2009**, *48*, 3598–3614. [CrossRef] [PubMed]

12. Neubert, P.; Meier, I.; Gaide, T.; Kuhlmann, R.; Behr, A. First telomerisation of piperylene with morpholine using palladium-carbene catalysts. *Catal. Commun.* **2016**, *77*, 70–74. [CrossRef]

13. Neubert, P.; Meier, I.; Gaide, T.; Behr, A. Additive-free palladium-catalysed hydroamination of piperylene with morpholine. *Synthesis* **2016**, *48*, 2287–2293.

14. Behr, A.; Neubert, P. Piperylene—A versatile basic chemical in catalysis. *ChemCatChem* **2014**, *6*, 412–428. [CrossRef]

15. Li, H.; Fang, X.; Jackstell, R.; Neumann, H.; Beller, M. Palladium-catalysed hydroamidocarbonylation of 1,3-dienes. *Chem. Commun.* **2016**, *52*, 7142–7145. [CrossRef] [PubMed]

16. Eom, D.; Park, S.; Park, Y.; Ryu, T.; Lee, P.H. Synthesis of indenes via Bronsted acid-catalyzed cyclization of diaryl-and alkyl aryl-1,3-dienes. *Org. Lett.* **2012**, *14*, 5392–5395. [CrossRef] [PubMed]

17. Clark, J.R.; Griffiths, J.R.; Diver, S.T. Ruthenium hydride-promoted dienyl isomerization: Access to highly substituted 1,3-dienes. *J. Am. Chem. Soc.* **2013**, *135*, 3327–3330. [CrossRef] [PubMed]

18. Liao, L.; Sigman, M.S. Palladium-catalyzed hydroarylation of 1,3-dienes with boronic esters via reductive formation of π-allyl palladium intermediates under oxidative conditions. *J. Am. Chem. Soc.* **2010**, *132*, 10209–10211. [CrossRef] [PubMed]
19. Raya, B.; Jing, S.; Balasanthiran, V.; RajanBabu, T.V. Control of selectivity through synergy between catalysts, silanes, and reaction conditions in cobalt-catalyzed hydrosilylation of dienes and terminal alkenes. *ACS Catal.* **2017**, *7*, 2275-2283. [CrossRef] [PubMed]

20. Sharma, R.K.; RajanBabu, T.V. Asymmetric hydrovinylation of unactivated linear 1,3-dienes. *J. Am. Chem. Soc.* **2010**, *132*, 3295-3297. [CrossRef] [PubMed]

21. Shibata, T.; Fujiwara, D.; Endo, K. Rh-catalyzed intermolecular and enantioselective [4 + 2] cycloaddition of 1,3-dienes with dimethyl acetylenedicarboxylate. *Org. Biomol. Chem.* **2008**, *6*, 464-467. [CrossRef] [PubMed]

22. Kotha, S.; Seema, V. Diversity-oriented synthesis of biaryl derivatives using cross-enyne metathesis, Diels Alder reaction, and Suzuki-Miyaura cross-coupling as key steps. *Synlett* **2011**, 2329-2334. [CrossRef]

23. Lewis, R.B.; de Alaniz, J.R. Nitrosocarbonyl hetero-Diels-Alder cycloaddition with 2-substituted 1,3-butadienes. *Tetrahedron* **2017**, *73*, 4045-4051. [CrossRef]

24. Srour, H.; Abidi, K.; Sahli, Z.; Sundararaju, B.; Hamdi, N.; Achard, M.; Bruneau, C. Dendralenes preparation via ene-yne cross-metathesis from in situ generated 1,3-enynes. *ChemCatChem* **2011**, *3*, 1876-1879. [CrossRef]

25. Nguyen, K.D.; Herkommer, D.; Krische, M.J. Enantioselective formation of all-carbon quaternary centers via C-H functionalization of methanol: Iridium-catalyzed diene hydrohydroxymethylation. *J. Am. Chem. Soc.* **2016**, *138*, 14210-14213. [CrossRef] [PubMed]

26. Smejkal, T.; Han, H.; Breit, B.; Krische, M.J. All-carbon quaternary centers via ruthenium-catalyzed hydromethylation of 2-substituted butadienes mediated by formaldehyde: Beyond hydroformylation. *J. Am. Chem. Soc.* **2009**, *131*, 10366-10367. [CrossRef] [PubMed]

27. Nakayama, J.; Machida, H.; Saito, R.; Akimoto, K.; Hoshino, M. Efficient preparation of polysubstituted 1,3-dienes. *Chem. Lett.* **1985**, *14*, 1173-1176. [CrossRef]

28. Hu, Y.; Li, N.; Li, G.; Wang, A.; Cong, Y.; Wang, X.; Zhang, T. Solid acid-catalyzed dehydration of pinacol derivatives in ionic liquid: Simple and efficient access to branched 1,3-dienes. *ACS Catal.* **2017**, *7*, 2576-2582. [CrossRef]

29. Böhmer, J.; Grigg, R. Pd(0)-catalysed formation of diarylated dienes from propargyl carbonates and organoboron and organotin(IV) reagents. *Tetrahedron* **1999**, *55*, 13463-13470. [CrossRef]

30. Green, N.J.; Willis, A.C.; Sherburn, M.S. Direct cross-coupling of propargylic diols. *Angew. Chem. Int. Ed.* **2016**, *55*, 9244-9248. [CrossRef] [PubMed]

31. Ishino, Y.; Nishiguchi, I.; Takihira, F.; Hirashima, T. Novel synthesis of 2,3-diarylbuta-1,3-dienes from 1,4-dimethoxybutyne-2. *Tetrahedron Lett.* **1980**, *21*, 1527-1528. [CrossRef]

32. Li, J.; Li, S.; Jia, X. Direct one-pot synthesis of 2,3-diarylbuta-1,3-dienes via self-coupling of acetophenones. *Synlett* **2008**, 1529-1531. [CrossRef]

33. Addie, M.S.; Taylor, R.J.K. 1,3-Dienes from ketones via the Shapiro reaction. *ARKIVOC* **2000**, *2000*, 660-666.

34. Ojha, D.P.; Prabhu, K.R. Pd-catalyzed cross-coupling reactions of hydrazones: Regioselective synthesis of highly branched dienes. *J. Org. Chem.* **2013**, *78*, 12136-12143. [CrossRef] [PubMed]

35. Jiang, H.; He, L.; Li, X.; Chen, H.; Wu, W.; Fu, W. Facile synthesis of dibranched conjugated dienes via palladium-catalyzed oxidative coupling of N-tosylhydrazones. *Chem. Commun.* **2013**, 9218-9220. [CrossRef] [PubMed]

36. Amaya, T.; Suzuki, R.; Hirao, T. Quinonediimines as redox-active organocatalysts for oxidative coupling of aryl- and alkenylmagnesium compounds under molecular oxygen. *Chem. Commun.* **2016**, *52*, 7790-7793. [CrossRef] [PubMed]

37. Lee, P.H.; Seomoon, D.; Lee, K. Palladium-catalyzed inter- and intramolecular coupling reactions of aryl and vinyl halides mediated by indium. *Org. Lett.* **2005**, *7*, 343-345. [CrossRef] [PubMed]

38. Contreras-Celedon, C.A.; Rincon-Medina, J.A.; Mendoza-Rayo, D.; Chacon-Garcia, L. Oxidative homocoupling of arylboronic acids catalyzed by a 4-aminoantipyrine-Pd(II) complex. *Appl. Organomet. Chem.* **2015**, *29*, 439-442. [CrossRef]

39. Ikeda, Z.; Oshima, K.; Matsuatma, S. Preparation and reaction of 2-aryl-3-silyl-1,3-butadiene. *Org. Lett.* **2005**, *7*, 4859-4861. [CrossRef] [PubMed]

40. Shimizu, M.; Kurahashi, T.; Shimono, K.; Tanaka, K.; Nagao, I.; Kiyomoto, S.-I.; Hiyama, T. Facile synthesis and palladium-catalyzed cross-coupling reactions of 2,3-bis(pinacolatoboryl)-1,3-butadiene. *Chem. Asian J.* **2007**, *2*, 1400-1408. [CrossRef] [PubMed]
41. Ansari, N.H.; Dacko, C.A.; Akhmedov, N.G.; Söderberg, B.C.G. Double Palladium Catalyzed Reductive Cyclizations. Synthesis of 2,2'-, 2,3'-, and 3,3'-Bi-1H-indoles, Indolo[3,2-b]indoles, and Indolo[2,3-b]indoles. *J. Org. Chem.* **2016**, *81*, 9337–9349. [CrossRef] [PubMed]

42. Fischmeister, C.; Bruneau, C. Ene-yne cross-metathesis with ruthenium carbene catalysts. *Beilstein J. Org. Chem.* **2011**, *7*, 156–166. [CrossRef] [PubMed]

43. Mori, M. Enyne metathesis. *Top. Organomet. Chem.* **1998**, *1*, 133–154.

44. Mori, M. Ruthenium-catalyzed ROM, RCM and CM of enyne. *J. Mol. Catal. A: Chem.* **2004**, *213*, 73–79. [CrossRef]

45. Diver, S.T.; Griffiths, J.R. Ene-yne metathesis. In *Olefin Metathesis: Theory and Practice*; Grela, K., Ed.; John Wiley & Sons: Hoboken, NJ, USA, 2014; pp. 153–185. ISBN 978-1-118-20794-9.

46. Kinoshita, A.; Sakakiatma, N.; Mori, M. Novel 1,3-diene synthesis from alkyne and ethylene by ruthenium-catalyzed enyne metathesis. *J. Am. Chem. Soc.* **1997**, *119*, 12388–12389. [CrossRef]

47. Galan, B.R.; Giessert, A.J.; Keister, J.B.; Diver, S.T. Studies on the mechanism of intermolecular enyne metathesis: Kinetic method and alkyne substituent effect. *J. Am. Chem. Soc.* **2005**, *127*, 5762–5763. [CrossRef] [PubMed]

48. Griffiths, J.R.; Keister, J.B.; Diver, S.T. From resting state to the steady state: Mechanistic studies of the ene-yne metathesis promoted by the Hoveyda complex. *J. Am. Chem. Soc.* **2016**, *138*, 5380–5391. [CrossRef] [PubMed]

49. Smulik, J.A.; Diver, S.T. Expanded scope in ethylene-alkyne cross-metathesis: Coordinating heteroatom functionality at the propargylic position. *Org. Lett.* **2000**, *2*, 2271–2274. [CrossRef] [PubMed]

50. Smulik, J.A.; Diver, S.T. Terminal-alkyne-ethylene cross-metathesis: Reaction of 1-substituted propargyl esters at elevated ethylene pressure. *J. Org. Chem.* **2000**, *65*, 1788–1792. [CrossRef] [PubMed]

51. Kinoshita, A.; Sakakiatma, N.; Mori, M. Novel 1,3-diene synthesis from alkyne and ethylene by ruthenium-catalyzed enyne metathesis. *Tetrahedron* **1999**, *55*, 8155–8167. [CrossRef]

52. Achard, M.; Derrien, N.; Demerseman, B.; Zhang, H.-J.; Bruneau, C. Ruthenium-catalyzed synthesis of functionalized 1,3-dienes. *Org. Lett.* **2009**, *11*, 185–188. [CrossRef] [PubMed]

53. Tonogaki, K.; Mori, M. An improved 1,3-diene synthesis from alkyne and ethylene using cross-enyne metathesis. *Tetrahedron Lett.* **2002**, *43*, 2235–2238. [CrossRef]

54. Lauchli, R.; Shea, K.J. A synthesis of the Welwistatin core. *Org. Lett.* **2006**, *8*, 5287–5289. [CrossRef] [PubMed]

55. Karabulut, S.; Sariaslan, B.; Öztürk, B.Ö. A ruthenium-based catalytic system with switchable selectivity between cyclotrimerization and enyne metathesis/Diels-Alder reactions of terminal alkynes. *Catal. Commun.* **2013**, *41*, 12–16. [CrossRef]

56. Sauvage, X.; Borguet, Y.; Noels, A.F.; Delaude, L.; Demonceau, A. Homobimetallic Ruthenium–N-Heterocyclic carbene complexes: Synthesis, characterization, and catalytic applications. *Adv. Synth. Catal.* **2007**, *349*, 255–265. [CrossRef]

57. Hilt, G.; Roesner, S. Substrate-controlled regioselective cobalt(I)-catalysed 1,4-hydrovinylation reactions. *Synthesis* **2011**, *4*, 662–668. [CrossRef]

58. Yi, C.S.; Lee, D.W.; Chen, Y. Hydrovinylation and [2 + 2] cycloaddition reactions of alkynes and alkenes catalyzed by a weel-defined cationic ruthenium-alkylidene complex. *Organometallics* **1999**, *18*, 2043–2045. [CrossRef]

59. Miao, X.; Fischmeister, C.; Bruneau, C.; Dixneuf, P.H. Dimethyl carbonate: An eco-friendly solvent in ruthenium-catalyzed olefin metathesis transformations. *ChemSusChem* **2008**, *1*, 813–816. [CrossRef] [PubMed]

60. The lower reactivity of first generation catalyst in ene-yne cross-metathesis with ethylene had previously been established with propargylic esters. See Ref. [45].

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