Diastereo- and enantioselective 1,3-hydrofunctionalization of trisubstituted alkenes by a directing relay.

Abstract

Catalytic alkene hydrofunctionalization is arguably one of the most fundamentally important methodologies to construct diverse C-X bonds with concomitant creation of stereogenic centres. While most catalytic hydrofunctionalization methodologies create a single stereocentre or vicinal stereocentres through 1,2-addition, channelling hydrofunctionalization to 1,3-addition mode to create non-adjacent stereocentres with simultaneous controls of both relative and absolute configurations represents a notable challenge. Here we report a catalytic 1,3-hydrofunctionalization of unactivated trisubstituted alkenes to generate enantiopure products containing α and γ stereocentres. An amide group on the alkene first directs the catalyst to cleave the methylene C-H bond enantioselectively, delivering an allylic stereocentre through C-H transposition. The amide remains bound to the metal centre, subsequently directing the catalyst to hydrofunctionalize the resulting alkene with high regiochemical and stereochemical controls. The separate stereocontrols in this 'directing relay' enables stereodivergent access to 1,3-hydroalkynylation products, in which all four possible stereoisomers are obtained with excellent diastereoselectivities and enantioselectivities.