A new methodology for synthesis of a chiral phosphinocarboxylic acid through Michael cyclization-aldol tandem reaction of chiral alpha,beta,chi,psi-unsaturated bisphosphine oxide and application in palladium-catalyzed asymmetric allylic alkylation.

Abstract

Upon successive treatment with lithium diisopropylamide and then benzaldehyde, a chiral alpha,beta,psi,omega-unsaturated bisphosphine oxide underwent Michael cyclization-aldol tandem reaction to afford the corresponding endo-alpha,beta-unsaturated cyclic bisphosphine oxides. Sequential stereoselective reduction and Horner-Wadsworth-Emmons olefination gave the corresponding monophosphine oxide. Oxidative conversion of an olefin moiety into a carboxyl group and subsequent deoxygenation of an oxide gave the corresponding chiral phosphinocarboxylic acid, which was successfully applied as a chiral and functionalized monophosphine ligand in a palladium-catalyzed asymmetric allylic alkylation.