Ni/Cu-Catalyzed Decarboxylative Addition of Alkynoic Acids to Terminal Alkynes for the Synthesis of gem-1,3-Enynes Sehyeon Han, † Han-Sung Kim, † Maosheng Zhang, ‡ Yuanzhi Xia,* ,‡ and Sunwoo Lee* ,† † Department of Chemistry, Chonnam National University, Gwangju 61186, Republic of Korea ‡ College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang Province 325035, P. R. China * S Supporting Information ABSTRACT: The synthesis of gem-1,3-enynes via Ni/Cu-catalyzed decarboxylative addition of alkynoic acids to terminal alkynes has been developed. It was found that the decarboxylation of an alkynoic acid led predominantly to gem-1,3-enynes instead of 1,3- diynes, which have been known to be formed through the coupling of terminal alkynes. A variety of gem-1,3-enynes were obtained in good yields. This catalytic system exhibited excellent regioselectivity and high functional group tolerance. C onjugated 1,3-enynes are important structural units in synthetic chemistry, materials science, and bioactive product synthesis. 1 A number of synthetic methods for the preparation of 1,3-enynes have been reported, 2 including the Wittig reaction with propargyl aldehydes 3 and dehydration of propargyl alcohols 4 (Scheme 1a,b). In terms of atom economy and availability of starting materials, direct catalytic coupling is very attractive. In this context, transition metal-catalyzed reactions of alkenes with terminal alkynes and hydroalkynation of alkynes have been developed (Scheme 1c). 5 The cross- dimerization of two different terminal alkynes has been challenging because a number of isomers can be formed and because it is difficult to control (Scheme 1d). To achieve different chemo-, regio-, and stereoselectivities, Ir, 6 Rh, 7 Ru, 8 Co, 9 Fe, 10 Pd, 11 and Ni 12 catalysts have been used. However, gem-selective cross-dimerization of alkynes, which occurs through head-to-tail cross-coupling, has been performed successfully only using Rh, 13 Ti, 14 and Pd 15 catalysts. Moreover, all of these methods have been limited to terminal alkynes. We have been developing a number of synthetic methods that use alkynoic acids, including transition metal-catalyzed decarboxylative coupling reactions. 16 Since simple preparation methods for aryl alkynoic acid derivatives were reported, decarboxylative reactions involving them have received much attention and have been widely applied in organic synthesis. 17 There are very few examples of metal-catalyzed coupling reactions between alkynoic acids and terminal alkynes in which they show different reactivity. Recently, we reported metal-free synthesis of propargyl amines and selective synthesis of (Z)- allyl nitriles and showed that only alkynoic acid derivatives afforded the desired products under our optimal conditions. 18 These results and the advantages of aryl alkynoic acids stimulated our interest in developing new synthetic methods using these compounds. In the course of our studies of novel reactions using alkynoic acid derivatives, we found that alkynoic acids provide gem-1,3- enynes when they are allowed to react with terminal alkynes in the presence of Ni/Cu dual catalysts. Decarboxylative addition was preferred, and this preference is not in agreement with findings from other groups. Lei demonstrated that two different terminal alkynes afforded 1,3-diynes in the presence of Ni and Cu catalysts. In 2016, Zhou, Yin, and co-workers reported the selective heterocoupling of terminal alkynes in the presence of a copper catalyst (Scheme 2a). 19 However, 1,3- enynes were not found in either report. Hence, our finding is very interesting and represents the first synthesis of gem-1,3- enynes through a decarboxylative coupling reaction and the Received: May 7, 2019 Published: June 5, 2019 Scheme 1. Synthesis of 1,3-Enynes Letter pubs.acs.org/OrgLett Cite This: Org. Lett. 2019, 21, 5426-5431 © 2019 American Chemical Society 5426 DOI: 10.1021/acs.orglett.9b01625 Org. Lett. 2019, 21, 5426-5431 Downloaded via CHONNAM NATL UNIV on July 28, 2019 at 21:56:58 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.