Mechanism of Copper-Catalyzed Hydroalkylation of Alkynes: An Unexpected Role of Dinuclear Copper Complexes

This article describes
a mechanistic study of copper-catalyzed
hydroalkylation of terminal alkynes. Relying on the established chemistry
of N-heterocyclic carbene copper hydride (NHCCuH) complexes, we previously
proposed that the hydroalkylation reaction proceeds by hydrocupration
of an alkyne by NHCCuH followed by alkylation of the resulting alkenylcopper
intermediate by an alkyl triflate. NHCCuH is regenerated from NHCCuOTf
through substitution with CsF followed by transmetalation with silane.
According to this proposal, NHCCuH must react with an alkyne faster
than with an alkyl triflate to avoid reduction of the alkyl triflate.
However, we have determined that NHCCuH reacts with alkyl triflates
significantly faster than with terminal alkynes, strongly suggesting
that the previously proposed mechanism is incorrect. Additionally,
we have found that NHCCuOTf rapidly traps NHCCuX (X = F, H, alkenyl)
complexes to produce (NHCCu)2(μ-X)­(OTf) (X = F, H,
alkenyl) complexes. In this article, we propose a new mechanism for
hydroalkylation of alkynes that features dinuclear (NHCCu)2(μ-H)­(OTf) (X = F, H, alkenyl) complexes as key catalytic intermediates.
The results of our study establish feasible pathways for the formation
of these intermediates, their ability to participate in the elementary
steps of the proposed catalytic cycle, and their ability to serve
as competent catalysts in the hydroalkylation reaction. We also provide
evidence that the unusual reactivity of the dinuclear complexes is
responsible for efficient hydroalkylation of alkynes without concomitant
side reactions of the highly reactive alkyl triflates.