Palladium-catalyzed enantioselective alkenylation of acyclic alkenols: Broad scope with alkenyl bromides.

Abstract

Palladium-catalyzed enantioselective Heck alkenylation of acyclic alkenols offers a promising strategy for constructing highly valuable stereodefined alkenylated carbonyl compounds from simple precursors. However, precise control of site-selective β-hydride elimination in this transformation remains an unresolved challenge. We have developed a highly enantioselective intermolecular Heck reaction to encompass various alkenyl bromides and acyclic primary or racemic secondary alkenols. The success of this reaction is attributed to the use of chiral BINOL ligands substituted with halogens at the 3,3'-positions, which offer selective β-hydride elimination followed by migration of the catalyst along the alkyl chain to provide the alkenylated carbonyl products. Successive applications enable alkenylation of trisubstituted alkenols and stereodivergent access to four stereoisomers with excellent enantio- and diastereoselectivity. Mechanistic studies indicated that 3,3'-<i>di</i>-Cl-BINOL controlled both pathway and stereochemistry, enabling selective β-hydride elimination, ligand acceleration, and nonlinear amplification.