“Excited” Class I Aldolases: EDA ComplexMediated Photo-biocatalytic Enantioselective β‑Alkylationof Enals

The Class I aldolases are known to construct C–C bonds with high enantioselectivity via both natural enamine and promiscuous iminium ion intermediates. However, these enzymes were not explored beyond the nucleophilic or electrophilic addition reactions in the thermal domain. At this juncture, we successfully expanded the catalytic promiscuity of DERA-Michaelase (DERA-MA) towards enantioselective β-alkylation of enals enabled by the direct photoexcitation of their promiscuous iminium ion intermediates. This chemistry exploits potassium salts of readily available aryl(alkyl) acetic acids as alkyl radical precursors. These molecules swiftly donate an electron upon electron donor–acceptor (EDA) complexation with the photoexcited iminium ion species. The scope and synthetic applicability of the developed photo-biocatalytic process were demonstrated on a semipreparative scale with various donor and acceptor substrates. The resulting alkylated products (17 examples) were isolated with good yields (up to 89%) and high enantiopurity (up to >99% ee).