Investigation and optimization of metal- and organocatalyzed decarboxylative radical addition of carboxylic acids to Seebach-Beckwith dehydroalanine towards optically pure unnatural amino acids

Four decarboxylative conjugate radical addition methods, including recent and greener methods using Fe- and Eosin Y as photocatalysts, were examined using Seebach-Beckwith dehydroalanine as a radical acceptor. Head-to-head comparison of yields and purity suggests that Ir-photocatalyzed decarboxylation of carboxylic acids is the optimal method for syntheses involving resonance-stabilized radicals. However, approaches relying on cheaper Ni-, Fe-, and Eosin Y-catalyzed processes are quite viable for the conjugate addition of 1°, 2°, and 3° radicals. • Decarboxylative Michael addition to a dehydroalanine gives chiral amino acid analogs. • Different methods of radical generation give different yields depending on structure. • Fe-catalyzed radical formation woks well for tertiary radical Michael addition. • Ir-catalyzed photodecarboxylation is expensive but most versatile for dehydroalanines. • Cheaper Ni & eosin Y catalysis works for conjugate addition of 1°, 2°, & 3° radicals.