Enantioselective synthesis of constrained phenylalanine analogues

Constrained phenylalanine derivatives containing hydrophobic groups and hydrogen bond acceptor and/or donor functionalities were synthesized through a tandem palladium-mediated Heck reaction followed by a rhodium(II)-catalyzed asymmetric hydrogenation. Aryl bromides were found to be better substrates in providing products with higher purity and in good yield. The cesium carbonate-mediated cyclization proceeded smoothly in good yield and optical purity. Aryl iodides reacted selectively over bromides under Jeffery-type conditions (Pd(OAc)2, Bu4NCl, Et3N) providing an opportunity for further metal-mediated functionalization.

Constrained phenylalanine derivatives containing hydrophobic, hydrogen bond acceptor and/or donor functionalities were synthesized through a tandem palladium-mediated Heck reaction followed by a rhodium(II)-catalyzed asymmetric hydrogenation. Aryl bromides were found to be better substrates and provided products with higher purity and in good yield. The cesium carbonate-mediated cyclization proceeded smoothly in good yield and optical purity. Aryl iodides reacted selectively over bromides under Jeffery-type conditions (Pd(OAc)2, Bu4NCl, Et3N) providing an opportunity for further functionalization.