Hetero Diels-Alder Reaction of N-Aeyl Imines. I. The Reaction of N’-Thiobenzoyl- N,N-dimethylformamidine with Electron-Deficient Dienophiles. Stereochemical and Mechanistic Aspects

Abstract

The reaction of N’-thiobenzoyl-N,N-dimethylformamidine (I) with electron-deficient dienophiles was investigated. The reaction of I with N-substituted maleimides (II) afforded exo and endo 1:1 cycloadducts (III). The stereochemistry was determined by analysis of 1H-nuclear magnetic resonance (1H-NMR) spectral data based on the modified neglect of diatomic overlap (MNDO) optimized structures. An equilibrium was observed between the starting materials (I and II) and 1:1 cycloadducts (III). The reaction of I with II in the presence of acetic acid afforded thiazine derivatives (IV), through elimination of dimethylamine from the primary cycloadduct (III). The reactions of I with several electron-deficient dienophiles were also examined. The reaction behavior is discussed in terms of frontier molecular orbital (FMO) theory and kinetic factors. © 1993, The Pharmaceutical Society of Japan. All rights reserved.