Cycloaddition of nitrile oxides to cyclic and acyclic α,β-unsaturated amides.: Frontier orbital interactions and an unexpected steric drift determine regiochemistry

The regiochemistry of the cycloadditions of nitrile oxides to alpha,beta-unsaturated amides is determined by frontier orbital interactions and by a regiochemical drift due to steric effects. Cycloadditions to alpha,beta-unsaturated lactames afford mainly 4-carboxamido-isoxazolines with high regioselectivity. In cycloadditions to acyclic alpha,beta-unsaturated amides the regioselectivity relaxes and finally reverses in the case of N,N-disubstituted derivatives, because of the increasing steric congestion at the amine nitrogen. (C) 1999 Elsevier Science Ltd. All rights reserved.