A short and efficient synthesis of L-5,5,5,5',5',5'-hexafluoroleucine from N-Cbz-L-serine.
[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.
Anderson
James T
JT
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Toogood
Peter L
PL
Marsh
E Neil G
EN
D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D015394:Molecular Structure; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*
C428006:5,5,5,5',5',5'-hexafluoroleucine; C470642:N-carbobenzoxy-serine; D012694:Serine; D007930:Leucine