Biomimetic 1,2-amino migration via photoredox catalysis

Abstract

Synthetic organic chemists continually draw inspiration from biocatalytic processes to innovate synthetic methodologies beyond existing catalytic platforms. Within this context, although 1,2-amino migration represents a viable biochemical process, it remains underutilized within the synthetic organic chemistry community. Here we present a biomimetic 1,2-amino migration accomplished through the synergistic combination of biocatalytic mechanism and photoredox catalysis. This platform enables the modular synthesis of γ-substituted β-amino acids by utilizing abundant α-amino-acid derivatives and readily available organic molecules as coupling partners. This mild method features excellent substrate and functionality compatibility, affording a diverse range of γ-substituted β-amino acids (more than 80 examples) without the need for laborious multistep synthesis. Mechanistic studies, supported by both experimental observations and theoretical analysis, indicate that the 1,2-amino migration mechanism involves radical addition to α-vinyl-aldimine ester, 3-exo-trig cyclization and a subsequent rearrangement process. We anticipate that this transformation will serve as a versatile platform for the highly efficient construction of unnatural γ-substituted β-amino acids. Enzyme-catalysed 1,2-amino migration represents a viable biochemical process that is currently underutilized within the synthetic organic chemistry community. Building upon this biocatalytic mechanism, a biomimetic photoredox-catalysed 1,2-amino migration method has been developed. By integrating photoredox-catalysed conditions, this approach enables the modular synthesis of a diverse library of γ-substituted β-amino acids.