Premium
Solution‐, Solid‐Phase, and Fluorous Synthesis of β,β‐Difluorinated Cyclic Quaternary α‐Amino Acid Derivatives: A Comparative Study
Author(s) -
Fustero Santos,
SánchezRoselló María,
Rodrigo Vanessa,
SanzCervera Juan F.,
Piera Julio,
SimónFuentes Antonio,
del Pozo Carlos
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200702009
Subject(s) - stereocenter , chemistry , reagent , amino acid , nucleophile , metathesis , yield (engineering) , combinatorial chemistry , allylic rearrangement , peptide synthesis , ether , salt metathesis reaction , organic chemistry , solid phase synthesis , transesterification , dipeptide , peptide , catalysis , enantioselective synthesis , materials science , biochemistry , polymer , polymerization , metallurgy
The diastereoselective synthesis of cyclic β,β‐difluorinated α‐amino acid derivatives bearing a quaternary stereocenter is described. The process relies on the chemo‐ and diastereoselective addition of allylic organometallic reagents to fluorinated α‐imino esters and a subsequent ring‐closing metathesis reaction (RCM). Complete selectivity in the nucleophilic addition was achieved with ( R )‐phenylglycinol methyl ether as a chiral auxiliary. The resulting amino acids were introduced into peptide chains, which could facilitate the preparation of potentially bioactive dipeptide derivatives. In addition, the solution synthesis of these cyclic fluorinated α‐amino acids was successfully adapted to solid‐phase and fluorous‐phase techniques. The reaction times and final deprotection were clearly more favorable in the latter, in which a fluorous trimethylsilylethanol (TMSE) tag was used. The tag was then easily removed upon treatment with TBAF in a high‐yield transesterification process.