Light‐Driven Epimerization: Diastereoconvergent Synthesis of [ ¹² C, ¹³ C] β ²,³ ‐Amino Acids

ABSTRACT β ‐Amino acids are crucial building blocks for bioactive peptides and pharmaceuticals, wherein the stereochemistry of C 2 , C 3 ‐disubstituted β 2,3 ‐amino acids dictates the secondary structure of β ‐peptides. However, the diastereoselective synthesis of these scaffolds remains a formidable challenge. Herein, we report a novel photocatalytic cascade enabling the one‐pot hydrogenation, carboxylation, and epimerization of α , β ‐unsaturated imines. This method provides direct and highly diastereoselective (d.r. up to 35:1) access to valuable syn ‐ β 2,3 ‐amino acids. Time‐course analysis and DFT calculations reveal a unique light‐driven dynamic kinetic epimerization process that ensures stereoconvergence to the thermodynamically favored syn ‐isomer. Notably, this strategy also facilitates the facile synthesis of 13 C‐labeled syn ‐ β 2,3 ‐amino acids using commercially available 13 C‐sodium formate, achieving exceptional isotope incorporation (93%–98%) that surpasses existing 13 CO 2 ‐based methods. Furthermore, the system's utility is demonstrated through the gram‐scale synthesis of N‐unprotected α ‐amino acids from imines (11 g, 75% yield), more significantly, via a one‐pot procedure directly from diaryl ketones.