Cooperative Carbene Photocatalysis for -Amino Ester Synthesis

beta-Amino acids are useful building blocks of bioactive molecules, including peptidomimetics and pharmaceutical compounds. The current limited accessibility to beta(2,2)-type amino acids which bear an alpha-quaternary center has limited their use in chemical synthesis and biological investigations. Disclosed herein is the development of a new N-heterocyclic carbene/photocatalyzed aminocarboxylation of olefins, affording beta(2,2)-amino esters with high regioselectivity. The generation of nitrogen-centered radicals derived from simple imides via a sequence of deprotonation and single-electron oxidation allows for the subsequent addition to geminal-disubstituted olefins regioselectively. The intermediate tertiary radicals then cross-couple with a stabilized azolium-based radical generated in situ to efficiently construct the quaternary centers. Mechanistic studies, including Stern-Volmer fluorescence quenching experiments, support the proposed catalytic cycle.