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Enantiomerically Pure β‐Amino Acids: A Convenient Access to Both Enantiomers of trans ‐2‐Aminocyclohexanecarboxylic Acid
Author(s) -
Berkessel Albrecht,
Glaubitz Katja,
Lex Johann
Publication year - 2002
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 - 10.1002/1099-0690(200209)2002:17<2948::aid-ejoc2948>3.0.co;2-e
Subject(s) - chemistry , enantiomer , phenethylamine , amide , yield (engineering) , cyclohexane , amino acid , organic chemistry , stereochemistry , biochemistry , materials science , metallurgy
Enantiomerically pure trans ‐2‐aminocyclohexanecarboxylic acid is an important building block for helical β‐peptides. We report here that this amino acid can be obtained from trans ‐cyclohexane‐1,2‐dicarboxylic acid in good yield by a simple one‐pot procedure comprising cyclization to the anhydride, amide formation with ammonia, and a subsequent Hofmann‐type degradation with phenyliodine( III ) bis(trifluoroacetate) (PIFA) as the oxidant. The N ‐Fmoc‐ and N ‐BOC‐protected derivatives were obtained by treatment of the amino acid with Fmoc‐OSu and BOC 2 O, respectively. The N ‐BOC derivative could be prepared in even better overall yield by a one‐pot procedure leading directly from trans ‐cyclohexane‐1,2‐dicarboxylic acid to the N ‐BOC‐protected amino acid. Both enantiomers of the starting trans ‐1,2‐cyclohexanedicarboxylic acid can be obtained easily and in large quantities by separating commercially available racemic trans ‐1,2‐cyclohexanedicarboxylic acid using either ( R )‐ or ( S )‐1‐phenethylamine. X‐ray crystallography of the diastereomerically pure salt obtained from ( R )‐1‐phenethylamine revealed that the configuration of the diacid component is (1 R ,2 R ), and not (1 S ,2 S ) as reported in the literature. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)