(27a) Photoenzymatic Asymmetric Hydroamination of Simple Aliphatic Amines and Vinyl Arene Olefins

Given the ubiquity of chiral amines in bioactive molecules, the synthesis community at large is interested in the construction of such valuable molecules in an efficient and straightforward manner. Compared to traditional approaches for chiral amine synthesis, the hydroamination is underdeveloped due to the lack of significant thermodynamic driving force for product formation, ground state electrostatic repulsion between coupling partners, and high transition state energy barriers. Herein, we disclose an enantioselective photoenzymatic hydroamination for the coupling of simple aliphatic amines and vinyl arene olefins. Our system utilizes the photoinduced promiscuity of an engineered flavin-dependent ene-reductase to (1) access highly energetic nitrogen-centered radicals which overcome the traditional reaction barriers and (2) impose stereo- and chemoselective control over radical intermediates. This work expands the catalytic repertoire of photoenzymes for the construction of β-chiral amines and delivers different regioselectivity compared to other hydroamination methodologies.