Development of Enantioselective Lithium-Isothiourea-Boronate-Catalyzed Matteson Homologations

Our group's discovery of lithium-isothiourea-boronate-catalyzed Matteson homologations is chronicled. Chiral thiourea dual-hydrogen bond donors were initially found to promote enantioselective dichloromethyl boronate rearrangements, albeit with poor reproducibility. Systematic investigations of the fate of the thiourea led to the discovery that lithium-isothiourea-boronate derivatives were being generated in situ as highly enantioselective catalytically active species. The optimal lithium-isothiourea-boronate catalyst displays significant generality in the rearrangement of primary alkyl migrating groups, affording synthetically valuable α-chloro boronic ester products with consistently high enantioselectivities. The catalyst is proposed to act as a structurally rigid chiral framework that precisely positions two lithium cations to enable a dual-lithium-mediated chloride abstraction.