Asymmetric Reduction of Lactam-Based β-Aminoacrylates. Synthesis of Heterocyclic β2-Amino Acids

The ability to affect asymmetric reduction of heterocyclic beta-aminoacrylates 1 (n = 1-3) hag been assessed with pyrrolidine and piperidone variants generating the corresponding N-heterocyclic beta(2)-amino acids 3b and 5b with high enantioselectivity (>= 97% ee) using a Rh/WALPHOS catalyst combination. The use of the carboxylic acid substrate was essential; the corresponding esters do undergo reduction but led to racemic products. The seven-ring azepanone variant (as the carboxylic acid 9b) underwent reduction, but only a minimal level of asymmetric induction was observed.