Stereoselective synthesis of cyclobutyl α-aminocyclopropyl carboxylic acid derivatives

The highly stereoselective cyclopropanation of chiral cyclobutyl dehydro amino acids, synthesized from (-)-alpha -pinene or (-)-verbenone, has been achieved by means of a 1,3-dipolar cycloaddition with diazomethane. The proximity of the double bond to the neighbouring stereogenic center of the cyclobutyl moiety is crucial to obtain cyclopropanes as single diastereomers whose configuration has been determined by X-ray structural analysis. DFT theoretical calculations of the more stable conformations allow us to understand the pi -facial diastereoselection Els the result of steric hindrance by the gem-dimethyl substitutuents and the side chain of the cyclobutane-ring. Chiroptical properties of these products have been studied by ORD and CD techniques and their behavior in CSA-NMR experiments has been ascertained. (C) 2001 Elsevier Science Ltd. All rights reserved.