1.10 Boron-Centered Radicals

Boryl radicals have emerged as powerful radical intermediates in organic synthesis. This review summarizes recently developed transformations involving boryl radical species, including C—B bond formation reactions, reduction reactions, and radical catalysis.

Accumulation of an unprecedented 5′-deoxyadenos-4′-yl radical unmasks the kinetics of the radical-mediated C-C bond formation step in MoaA catalysis

Radical S-adenosyl-L-methionine (SAM) enzymes catalyze various free radical-mediated reactions. In these enzymes, the rate-determining SAM cleavage kinetically masks all the subsequent steps. Due to this kinetic masking, detailed mechanistic characterization of radical transformations catalyzed by these enzymes is very difficult. Here, we report a successful kinetic characterization of the radical C-C bond formation catalyzed by a MoaA radical SAM enzyme. MoaA catalyzes an unprecedented 3′,8-cyclization of GTP into 3′,8-cyclo-7,8-dihydro-GTP (3′,8-cH2GTP) during the molybdenum cofactor (Moco) biosynthesis. Through a series of EPR and biochemical characterization, we found that MoaA accumulates a 5′-deoxyadenos-4′-yl radical (5′-dA-C4′•) under the turnover conditions, and forms (4′S)-5′-deoxyadenosine ((4′S)-5′-dA), which is a C-4′ epimer of the naturally occurring (4′R)-5′-dA. Together with kinetic characterizations, these observations revealed the presence of a shunt pathway in which an on-pathway intermediate, GTP C-3′ radical, abstracts H-4′ atom from 5′-dA to transiently generate 5′-dA-C4′• that is subsequently reduced stereospecifically to yield (4′S)-5′-dA. Detailed kinetic characterization of the shunt and the main pathways provided the comprehensive view of MoaA kinetics, and determined the rate of the on-pathway 3′,8-cyclization step as 2.7 ± 0.7 s−1. Together with DFT calculations, this observation suggested that the 3′,8-cyclization is accelerated by 6 ∼ 9 orders of magnitude by MoaA. Potential contributions of the active-site amino acid residues, and their potential relationships with human Moco deficiency disease are discussed. This is the first determination of the magnitude of catalytic rate acceleration by a radical SAM enzyme, and provides the foundation for understanding how radical SAM enzymes achieve highly specific radical catalysis.

Recent advances in N-heterocyclic carbene-based radical catalysis

This minireview examines the history and state-of-the-art of the N-heterocyclic carbene-based radical catalysis.