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.