NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes and the ligand effects on regioselectivity

Difunctionalization of olefins is an ongoing and important focus of synthetic organic chemistry. Here the authors report a nickel-catalysed hydroalkylation of unactivated alkenes to obtain branched alkyl carboxylic acids or alkyl amines, using aminoquinoline and picolinamide as directing groups. Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation method applied to a broad range of unactivated alkenes remains challenging. Herein, we report a NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes to access beta- or gamma-branched alkyl carboxylic acids and beta-, gamma- or delta-branched alkyl amines. A broad range of alkyl iodides and bromides with different functional groups can be installed with excellent regiocontrol and availability for site-selective late-stage functionalization of biorelevant molecules. Under modified reaction conditions with NiCl2(PPh3)(2) as the catalyst, migratory hydroalkylation takes place to provide beta- (rather than gamma-) branched products. The keys to success are the use of aminoquinoline and picolinamide as suitable directing groups and combined experimental and computational studies of ligand effects on the regioselectivity and detailed reaction mechanisms.

Automated summary

The authors report a nickel-catalysed hydroalkylation of unactivated alkenes to obtain branched alkyl carboxylic acids or alkyl amines. The reaction shows excellent regioselectivity and allows for site-selective late-stage functionalization of biorelevant molecules. The success of the reaction relies on the use of suitable directing groups and the investigation of ligand effects and reaction mechanisms.