Novel synthetic route to 1,4-dihydropyridines from β-amino acrylates by using titanium(IV) chloride under facile conditions

The reactions of Boc-beta-amido- and beta-amino acrylates, in which the C=C possesses both nucleophilic and electrophilic sites, were investigated under acidic conditions. The trifluoroacetic-acid induced cyclization of the beta-amido acrylates to the corresponding oxazolidin-2-ones involves a rarely seen nucleophilic attack of the carbamate carbonyl group. The cyclotrimerization of beta-amino acrylates to N-substituted 1,4-dihydropyridines was observed in the presence of a Lewis acid. High yields of 1,4-dihydropyridines (70-83%) were readily obtained by using substoichiometric amount TiCl(4) under mild condition. The cyclotrimerization is presumably occurring via a Hantzsch related mechanism involving three addition/elimination reactions of the amphiphilically reactive C=C. (C) 2010 Elsevier Ltd. All rights reserved.