Radical Functionalization of Unsaturated Amino Acids: Synthesis of Side-Chain-Fluorinated, Azido-Substituted, and Hydroxylated Amino Acids

A range of enantiomerically pure protected side-chain-fluorinated amino acids has been prepared (13 examples) by treatment of protected amino acids containing unsaturated side chains with a combination of Fe(III)/NaBH₄ and Selectfluor. The modification of the conditions by replacement of Selectfluor with NaN₃ allowed the preparation of side-chain azido-substituted amino acids (five examples), which upon catalytic hydrogenation gave the corresponding amines, isolated as lactams (four examples). Radical hydration of the unsaturated side chains leading to side-chain-hydroxylated protected amino acids has also been demonstrated.