Toward Iridium-Catalyzed Asymmetric Branched-Selective α-Alkylation of Aldehydes with Unactivated Alkenes Enabled by a Pyrazole Mediator.

Abstract

Aldehyde α-alkylation remains a challenging transformation. On the other hand, given the wide availability of alkenes, it has been an attractive objective to use unactivated alkenes as alkylating agents. Here, as an initial model study, we report a stepwise asymmetric α-alkylation of aldehydes with simple alkenes as the coupling partner. The reaction is enabled by a distinct pyrazole mediator and catalyzed by a chiral cationic Ir complex. The C-H alkylation of the N-alkenyl pyrazole intermediates proceeded with excellent enantioselectivity and high branched selectivity. Preliminary mechanistic studies indicate that the branched selectivity is consistent with the involvement of an Ir-carbon migratory insertion pathway. This asymmetric alkylation method shows promise to simplify syntheses of chiral fragments of bioactive compounds.