Transition metal-catalyzed couplings of alkynes to 1,3-enynes: modern methods and synthetic applications

Abstract

The metal-catalyzed coupling of alkynes is a powerful method for the preparation of 1,3-enynes, compounds that are of broad interest in organic synthesis. Numerous strategies have been developed for the homo- and cross coupling of alkynes to enynes via transition metal catalysis. In such reactions, a major issue is the control of regio-, stereo-, and, where applicable, chemoselectivity. Herein, we highlight prominent methods for the selective synthesis of these valuable compounds. Further, we illustrate the utility of these processes through specific examples of their application in carbocycle, heterocycle, and natural product syntheses.

Cobalt‐Catalyzed Dimerization and Homocoupling of Terminal Alkynes

“…[3][4][5] In particular,d irect dimerization [6] and Glaserh omocoupling [7] of terminal alkynes are of significant interestd ue to their atom-economy assembling av ariety of useful organic compounds, such as 1,3-diynes [8] and 1,3-enynes. [9] In addition, these products are valuable building blocks for the synthesis of polysubstituted aromatic rings, drug intermediates and natural products.I np reviousr eported works, dimerizationo ft erminal alkynes often gave E-1,3-enynes [10] and Z-1,3-enynes, [11] and only af ew examples has been reportedg iving high selectivity.A lso, to our knowledge,t he efficient Glaser homocoupling of terminal alkynes catalyzed by cobalt complexes has rarely been developed.[12]Thus, we envisionedt hat cobaltc omplexes promoted reaction of terminal alkynes would provide alternative access to 1,3-diynes and Z-selective 1,3-enynes through fine tuningo f the ligand structure. In this regard,w eh erein describe cobaltcatalyzed dimerization/homocoupling of terminala lkynes in the presence of tBuOK, depending on the cobalt complexes and reaction conditions.…”

Terminal Alkyne Coupling Reactions through a Ring: Mechanistic Insights and Regiochemical Switching

“…Crystallographic (1,3,8)a nd high-resolution mass-spectrometry data were collected using instruments purchased through support from Advantage West Midlands and the European Regional Development Fund. ), the University of Warwick (R.E.A.…”

“…[1,2] These reactions involve the formal addition of the C(sp) À H bond of one alkyne across the C Cb ond of the other, aprocess that can in principle result in three different regioor stereochemical isomers: gem-, E-, and Z-enynes.W ith the additional possibility for the substrates to be consumed through competing metal-catalysed reaction pathways-for instance leading to butatrienes,a renes,o ro ther polyenesthe widespread application of terminal alkyne coupling reactions in organic synthesis rests on the development of catalysts that can enforce high reaction control. [1,2] These reactions involve the formal addition of the C(sp) À H bond of one alkyne across the C Cb ond of the other, aprocess that can in principle result in three different regioor stereochemical isomers: gem-, E-, and Z-enynes.W ith the additional possibility for the substrates to be consumed through competing metal-catalysed reaction pathways-for instance leading to butatrienes,a renes,o ro ther polyenesthe widespread application of terminal alkyne coupling reactions in organic synthesis rests on the development of catalysts that can enforce high reaction control.…”

“…[7] Although closely related Rh(PNP) and Rh(PCP) systems demonstrate reduced selectivity,they predominantly give mixtures of only gem-and E-enynes. [1] Motivated by these precedents and as part of our research exploring the organometallic chemistry of NHC-based pincer ligands, [10,11] we set about evaluating the use of rhodium complexes containing neutral lutidine-based CNC ligands in terminal alkyne coupling reactions.I np articular,w ew ere interested in ascertaining the capacity of macrocyclic variants for imparting additional reaction control. Thef ormation of Z-enynes instead typically evokes vinylidene intermediates.…”

Lactone Synthesis by Enantioselective Orthogonal Tandem Catalysis

“…Considering these factors,weenvisioned that an enantioselective alkyne addition process could be coupled with aregioselective alkyne heterofunctionalization via sequential s-a nd p-activations,b ut the catalyst(s) would need to effectively control these types of selectivity and also be chemoselective for reaction sequencing.M any types of enantioselective nucleophilic addition reactions of alkynes are known, [18] and we envisioned that the heteroatom incorporated into adduct 2 would be amenable to alkyne addition (e.g., 2!4/5 via 3,Scheme 1). This type of sequence would provide direct access to highly useful products, especially if 6-membered rings could be formed, considering their prevalence in bioactive natural products and the fact that there are few reports of favoring the 6-endo products.…”