Regio- and Enantioselective Alkoxycarbonylation of Unactivated Terminal Alkenes under Palladium-Bromide-Monophosphine...

Regio- and stereoselective hydrocarbonylation of unactivated alkenes, including abundant light olefins produced on a large scale and a diverse range of other commercial and synthetic materials, remains a formidable challenge in fine-chemical synthesis. Here, we report a highly regio- and enantioselective alkoxycarbonylation of a range of unactivated terminal olefins with a variety of alcohols, including biologically relevant motifs, to afford valuable chiral esters in typically >95:5 enantiomeric ratios, >95:5 regioisomeric ratios, and >80% yields. Chiral alcohols bearing adjacent stereogenic centers can be transformed into either diastereomer of the products with >92:8 diastereomeric ratios and >80% yields. Central to this method is a palladium-bromide catalyst featuring a newly developed valley-shaped monophosphorus ligand, ValleyPhos. The crystal structure of the precatalyst (ValleyPhos)PdBr₂ reveals that the chiral ligand forms a deep asymmetric pocket around the metal center, enabling precise enantiocontrol. The bromide ligand, in turn, is essential for achieving branched regioselectivity and suppressing deleterious chain-walking processes.