Pd-Catalyzed Asymmetric Hydroalkylation of 1,3-Dienes: Access to Unnatural α-Amino Acid Derivatives Containing Vicinal Quaternary and Tertiary Stereogenic Centers.

Abstract

Pd-phosphinooxazoline (Pd-PHOX)-catalyzed asymmetric hydroalkylation of 1,3-dienes with azlactones was successfully developed for the first time, affording various enantioenriched α-quaternary α-amino acid derivatives bearing contiguous quaternary and tertiary stereogenic centers in good yields with exclusive regioselectivity and excellent stereoselective control (up to 92% yield, >20:1 dr, and >99% ee). The scale-up catalytic asymmetric hydroalkylation was performed well without loss of reactivity and stereoselectivities, which exhibited great potential application. The synthetic utility of the current methodology was demonstrated through product transformations to access other biologically important compounds such as chiral β-amino alcohol and α-quaternary cyclic α-amino acid derivatives.