Synthesis of conformationally restricted 1,2,3-triazole-substituted ethyl β- and γ-aminocyclopentanecarboxylate stereoisomers. Multifunctionalized alicyclic amino esters

Stereoisomers of 1,2,3-triazole-functionalized, conformationally restricted beta- or gamma-amino esters with a cyclopentane skeleton were efficiently synthetized from the bicyclic beta-lactam 6-azabicyclo[3.2.0]hept-3-en-7-one (1) and Vince gamma-lactam (15) in five or six steps involving the azide-alkyne 1,3-dipolar cycloaddition of azido-substituted amino ester stereoisomers with nonsymmetric acetylenes. The azide-alkyne click reactions were investigated under thermal and Cu(I)-catalyzed conditions. Surprisingly, the thermally induced cycloaddition furnished the corresponding 1,4-triazoles regioselectively, which also took place selectively in response to Cu(I) catalysis. (C) 2010 Elsevier Ltd. All rights reserved.