Biomimetic 1,2-amino migration via photoredox catalysis
Wei‐Tai Fan, Yuang Cui, Bei‐Bei Zhan, Yizhou Chen, Lei Bao, Yufan Liang, Xiaheng Zhang
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.