Double 1,2-Migration of Bromine and Silicon in Directed C-H Alkynylation Reactions with Silyl-Substituted Alkynyl Bromides through an Iridium Vinylidene Intermediate

The iridium(III)-catalyzed C-H alkynylation of 2-acylimidazoles with alkynyl bromides, which was recently developed by our group, provides an efficient strategy for the construction of both C(sp)-C(sp(2)) and C(sp)-C(sp(3)) bonds. The mechanism for this reaction was extensively studied using density functional theory (DFT) calculations. The computed catalytic cycle is initiated by C-H activation, and the formed iridacycle undergoes a strain-controlled regioselective migratory insertion of an alkynyl bromide. The resulting alpha-bromovinyl iridium species is rapidly converted into a more stable iridium vinylidene intermediate by a 1,2-bromine migration, and the adjacent silyl group subsequently migrates to furnish a C-H-alkynylated product. The origin of the unique difference in reactivity with respect to the substituent on the alkynyl bromide is the 1,2-migration step, in which a silyl group can highly stabilize the transition state by the beta-silicon effect.

Automated summary

We have developed an iridium(III)-catalyzed C-H alkynylation reaction of 2-acylimidazoles with alkynyl bromides, which efficiently constructs both C(sp)-C(sp(2)) and C(sp)-C(sp(3)) bonds. The mechanism of this reaction was extensively studied using density functional theory (DFT) calculations. The calculated catalytic cycle starts with C-H activation, followed by a strain-controlled selectivity migratory insertion of an alkynyl bromide into the formed iridacycle. The resulting alpha-bromovinyl iridium species undergoes a rapid conversion into a more stable iridium vinylidene intermediate through a 1,2-bromine migration, and the adjacent silyl group migrates to give the C-H alkynylated product. The unique reactivity difference with respect to the substituent on the alkynyl bromide occurs during the 1,2-migration step, where a silyl group can highly stabilize the transition state through the beta-silicon effect.