Asymmetric synthesis of the stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate.
The stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate may be prepared stereoselectively from diester derivatives of (E,E)-octa-2,6-diendioc acid, with the key step utilising the conjugate addition of homochiral lithium N-benzyl-N- alpha-methylbenzylamide. The trans-C(1)-C(2)-stereoisomers are readily prepared via a diastereoselective tandem conjugate addition cyclisation protocol with lithium (R)-N-benzyl-N- alpha-methylbenzylamide, with subsequent hydrogenolysis and ester hydrolysis giving the (1R,2R,5R)- and (1R,2R,5S)- beta-amino diacids in good yields. The preparation of the cis-C(1)-C(2)-stereoisomers utilises a protocol involving N-oxidation and Cope elimination of the major diastereoisomeric product arising from conjugate addition and cyclisation, giving homochiral (R)-5-carboxymethyl-cyclopentene-1-carboxylate. Conjugate addition of either lithium (R)- or (S)-N-benzyl-N- alpha-methylbenzylamide to (R)-5-carboxymethyl-cyclopentene-1-carboxylate, and diastereoselective protonation with 2,6-di-tert-butyl phenol gives, after hydrogenolysis and ester hydrolysis, the (1S,2R,5R)- and (1R,2S,5R)- beta-amino diacids in good yield. The use of (S)-N-benzyl-N- alpha-methylbenzylamide in the initial conjugate addition and cyclisation reaction, and subsequent repetition of the elimination and conjugate addition strategy allows stereoselective access to all stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate.
Urones
Julio G
JG
Departamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008, Salamanca, Spain. nmg@usal.es
Garrido
Narciso M
NM
Díez
David
D
El Hammoumi
Mohamed M
MM
Dominguez
Sara H
SH
Antonio Casaseca
J
J
Davies
Stephen G
SG
Smith
Andrew D
AD