Work

Radical Disconnection Logic Enables Direct Conversion of α-Amino Acids into Differentiated Vicinal Diamines

Year: 2026

Type: article

Abstract: Functional group interconversions (FGIs) are foundational to synthesis, yet classical acid-to-aminomethyl transformations remain intrinsically step- and redox-intensive. Here we introduce a radical disconnection strategy that enables the direct conversion of α-amino acids into differentiated vicinal diamines in a single step. The method relies on photocatalytic decarboxylation of readily available amino acids to generate α-amino radicals, which are selectively trapped by an in situ-formed, unstabilized N-protected formimine, a transient and previously inaccessible aminomethyl equivalent. This operationally simple approach circumvents harsh hydride reductions, tolerates hydride-sensitive functionalities, and offers broad generality. The robustness of the reaction is showcased by safe and intensified continuous-flow scale-up, with a >400-fold increase in space-time yield. Moreover, the differentiated diamines allow selective downstream functionalization and provide streamlined access to fragments of pharmaceutically active molecules. This work establishes radical disconnection as a powerful blueprint for redox-economical FGIs and unlocks a direct route to privileged vicinal diamine architectures.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.6c16323