Nucleophilic Attacks on Carbon-Carbon Double Bonds. 33. Approaching the Retention Region from the Stereoconvergence Region in Nucleophilic Substitution of (E)- and (Z)-Methyl p-Substituted α-Formyl- and α-(tert-Butoxycarbonyl)-β-halocinnamates

Article abstract of DOI:10.1021/jo00372a005

The three E/Z pairs of the highly electrophilic vinyl halides β-chloro-α-(methoxycarbonyl)-p-nitrocinnamaldehydes (6), tert-butyl methyl β-bromo(p-methylbenzylidene)- (21) and β-bromo(p-nitrobenzylidene)malonates (26) were prepared and separated.The structures of (E)-6 and (E)-21 and of intermediates in their synthesis were determined by X-ray crystallography.The stereochemistry of the substitution of the halogen by p-toluenethiolate (TolS^-) and p-cresolate (TolO^-) ions was investigated by using 1H NMR as the stereochemical probe.Substitution of 6 in Me2SO-d6 by TolS^- proceeds with nearly complete stereoconvergence, whereas substitution by TolO^- proceeds with high extent of, but not complete, retention of configuration.Cl^--assisted (E)-6<*>(Z)-6 isomerization was observed.The substitution of (E)- and (Z)-21 in Me2SO-d6 and of (E)- and (Z)-26 in 95:5 CD3CN-Me2SO-d6 by TolS^- proceeds with complete retention of configuration and by TolO^- with nearly complete retention.The results are discussed in terms of the multistep route of vinylic substitution via an intermediate carbanion.They corroborate the predictions of the variable transition-state theory in nucleophilic vinylic substitution that stereoconvergence will be observed for highly activated systems and that the stereochemistry should be gradually changed to retention when the electrophilicity of the vinyl halide is decreased and near the borderline when the nature of the nucleophile is changed.Comparison with other systems for which stereoconvergence was observed raises the question of the structural borderline between stereoconvergence and retention, and predictions for the stereochemical outcome in substitutions ofsystems not yet studied are given.Some stereochemical aspects of the condensation, bromine addition, and HBr elimination in the reactions leading to 21 and 26 are briefly discussed.