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A short and efficient synthesis of L-5,5,5,5',5',5'-hexafluoroleucine from N-Cbz-L-serine
James T Anderson1, Peter L Toogood, E Neil G Marsh
1Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Abstract:
[reaction: see text] 5,5,5,5',5',5'-Hexafluoroleucine (6), a fluorous analogue of leucine, is of considerable interest as a building block in the design of fluorous proteins and peptides. We report a short and efficient synthesis of 6, which is obtained from N-Cbz-L-serine (1) in 50% overall yield, 99% enantiomeric excess, and in multigram quantities. Key steps are addition of a serine-derived organozincate to hexafluoroacetone to construct the hexafluoroleucine side chain, followed by radical-mediated deoxygenation of the resulting tertiary alcohol.
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