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

摘要

Pd-phosphinooxazoline (Pd-PHOX)-catalyzed asymmetric hydroalkylation of 1,3-dienes with azlactones was successfully developed for the first time, affording various enantioenriched alpha-quaternary alpha-amino acid derivatives bearing contiguous quaternary and tertiary stereogenic centers in good yields with exclusive regioselectivity and excellent stereo selective 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 beta-amino alcohol and alpha-quaternary cyclic alpha-amino acid derivatives.