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Asymmetric Synthesis of γ‐Fluorinated α‐Amino Acid Derivatives
Author(s) -
Shendage Deepak M.,
Fröhlich Roland,
Bergander Klaus,
Haufe Günter
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400665
Subject(s) - chemistry , racemization , deamidation , hydrolysis , alkylation , derivative (finance) , enantioselective synthesis , organic chemistry , amino acid , acid hydrolysis , medicinal chemistry , catalysis , enzyme , biochemistry , financial economics , economics
Asymmetric alkylation of ( S )‐Boc‐BMI ( 1a , BMI = 2‐ tert ‐butyl‐3‐methylimidazolidin‐4‐one) and its α‐methyl derivative 1b with 2‐fluoroallyl tosylate, subsequent mild acidic deprotection of the products 2a and 2b , and basic hydrolysis of the thus formed N ‐methylamides 4a and 4b gave ( S )‐2‐amino‐4‐fluoropent‐4‐enoic acid ( 5a ) and ( S )‐2‐amino‐4‐fluoro‐2‐methylpent‐4‐enoic acid ( 5b ). Basic hydrolysis of compound 4a was accompanied by partial racemization, which was overcome by applying a new stereoconservative deamidation procedure. The alkylated cis ‐configured product 2a formed under kinetic control epimerized on refluxing with 2 n NaOH to give the thermodynamically more stable trans isomer 9 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)