Tetrasubstituted allenes via the palladium-catalysed kinetic resolution of propargylic alcohols using a supporting ligand

Abstract

Efficient enantioselective construction of fully substituted allenes from simple starting materials is still a fundamental challenge due to the difficulty to discriminate between the four substituents at the 1- and 3-positions of the three-carbon axis of chirality. Here, we report a straightforward catalytic asymmetric synthesis of tetrasubstituted 2,3-allenoic acids from readily available racemic propargylic alcohols. Enabled by the co-catalysis of palladium and a Bronsted acid in the presence of a commercially available chiral ligand (DTBM-SEGphos) and an achiral monophosphine supporting ligand (PPh3), the kinetic resolution of propargylic alcohols proceeded efficiently in the presence of water and 1 atm CO, affording tetrasubstituted 2,3-allenoic acids in excellent enantioselectivity and atom economy with a good functional group compatibility. Performing a second kinetic resolution on the unreacted alcohol gave access to the other enantiomer of the product. These allenes are precursors to compounds with quaternary carbon centres and other chiral tetrasubstituted allene building blocks, which are of great interest. Asymmetric routes for the formation of tetrasubstituted allenes are scarce and limited in scope. Now, a catalytic asymmetric process is reported giving access to tetrasubstituted allenes from readily available propargylic alcohols, and a potential role for an achiral supporting ligand is postulated.