Improved synthesis of (2S,5S)-5-tert-butylproline

(2S,5S)-N-Boc-5-tert-butylproline (1) was synthesized by an improved proced ure featuring the conversion of (2S)-1-tert-butyl-dimethylsiloxy-2-N-(PhF)a mino-5-oxo-6,6-dimethylheptane (16) into its corresponding imino alcohol fo llowed by directed hydride delivery to reduce the imine functionality with a 95:5 diastereoselectivity. Ketone 16 was obtained from methyl 2-N-(PhF)am ino-5-oxo-6,6-dimethylheptanoate (13), a previously reported precursor for the synthesis of (2S,SR)-5-tert-butylproline, by reduction to its correspon ding diol, selective protection of the primary alcohol and oxidation of the secondary alcohol. This route provided (2S,SS)-N-Boc-5-tert-butylproline ( 1) of > 96% enantiomeric purity suitable for peptide chemistry in 39% overa ll yield from ketone 13. (C) 2001 Elsevier Science Ltd. All rights reserved .