Carboxylate Switch between Hydro‐ and Carbopalladation Pathways in Regiodivergent Dimerization of Alkynes

Abstract

Experimental and theoretical investigation of the regiodivergent palladium-catalyzed dimerization of terminal alkynes is presented. Employment of N-heterocyclic carbene-based palladium catalyst in the presence of phosphine ligand allows for highly regio- and stereoselective head-to-head dimerization reaction. Alternatively, addition of carboxylate anion to the reaction mixture triggers selective head-to-tail coupling. Computational studies suggest that reaction proceeds via the hydropalladation pathway favoring head-to-head dimerization under neutral reaction conditions. The origin of the regioselectivity switch can be explained by the dual role of carboxylate anion. Thus, the removal of hydrogen atom by the carboxylate directs reaction from the hydropalladation to the carbopalladation pathway. Additionally, in the presence of the carboxylate anion intermediate, palladium complexes involved in the head-to-tail dimerization display higher stability compared to their analogues for the head-to-head reaction.

Palladium‐Catalyzed Tail‐to‐Tail Reductive Dimerization of Terminal Alkynes to 2,3‐Dibranched Butadienes

“…Among them, the dimerization of terminal alkynes as an atom‐economic and straightforward method for synthesizing conjugated enynes, [2] dienes, [3] and diynes [4] has attracted considerable interest. The dimerization of terminal alkynes through head‐to‐tail [2d,f,g,i–k,p] and head‐to‐head [2e–i,l–o,3,4] processes has been established in the presence of catalytic or stoichiometric amounts [3] of transition metals. As far as we know, tail‐to‐tail reductive dimerization of terminal alkynes for the generation of 2,3‐dibranched butadienes hasn't been reported (Scheme 1).…”

Pseudo‐tetrahedral Rhodium and Iridium Complexes: Catalytic Synthesis of E‐Enynes

“…Two main mechanistic pathways are recognized for alkyne dimerization . The first one involves oxidative addition of the C−H bond generating a rhodium‐alkynyl‐hydride complex, followed by coordination of a second alkyne and either insertion of the coordinated alkyne into the M−H bond (hydrometalation) or into the M−C bond (carbometalation) and subsequent reductive elimination to afford the enyne.…”

“…A plausible mechanism for the dimerization of alkynes by using complex 2 as catalyst precursor is shown in Scheme . Only the hydrometalation path has been considered because this step is typically lower in energy than the carbometalation …”

Regiodivergent Catalysis: A Powerful Tool for Selective Catalysis

“…In examples 5 and 6, regioselectivity of the transformations of achiral substrates is achieved by non‐identical catalysts. They are generated from common precursors by changing the solvent and anionic ligand, respectively . Therefore, these three sets of reactions are chemically different, highly regioselective transformations.…”