Catalyst-free reactions of anilines with β-chloroenones: synthesis of α-chloroenaminones and 1,4-benzodiazepines

The Michael addition of anilines to β-chloroenones gives enaminones by the elimination of hydrochloric acid (HCl). These enaminones are transformed into α-chloroenaminones via in situ sp² C-H functionalization. Anilines that are attached to an electron-donating group react more readily with β-chloroenone to give the corresponding products in excellent yields. A highly atom-economical method has been developed using dimethyl sulfoxide (DMSO) as a green oxidant and solvent. The desired α-functionalized enaminones are formed in good yields with excellent Z-selectivity. We have established the generality of this reaction with many substrates, and scaled-up reactions have been performed to showcase the practical applications. A catalyst-free double annulation of β-chloroenones with o-phenylenediamine has also been demonstrated for the synthesis of 1,4-benzodiazepine derivatives in moderate yields under mild reaction conditions.