Simple and efficient syntheses of Boc- and Fmoc-protected 4(R)- and 4(S)-fluoroproline solely from 4(R)-hydroxyproline

As building blocks of collagen model peptides, Boc- and Fmoc-protected 4(R)- and 4(S)-fluoroproline, which will be widely used in peptide synthesis including solid-phase strategy, were synthesized from the readily available 4(R)-hydroxyproline in higher yield than with conventional methods. To establish the stereospecificity of the Mitsunobu reaction and the subsequent fluorination that were presumed to cause the inversion of configuration at the C-4 position of a proline derivative, the absolute configuration of one of the key products, Boc-4(S)-fluoroproline, was determined by X-ray crystallography.