One-Pot Synthesis of 2-Acylindole-3-acetylketones via Domino Aza-alkylation/Michael Reaction Using o-Aminophenyl α,β-Unsaturated Ketones Followed by Desulfonative Dehydrogenation

The development of novel and practical synthetic methods with a minimum number of operations for the construction of bioactive structurally complex compounds is a major challenge in synthetic organic chemistry. Recently, we reported an efficient method for the stereoselective synthesis of 2,3-disubstituted indoline derivatives; cis-2,3-disubstituted indolines were obtained by the aza-alkylation/Michael cascade reaction of 2-(tosylamino)phenyl α,β-unsaturated ketones with α-bromoacetophenones in good yields and with excellent diastereoselectivities (Scheme 2, Eq. (1)). Among the available synthetic strategies, domino or cascade reactions have received wide acceptance as highly efficient and powerful methods for the synthesis of molecules with a high structural complexity. An efficient synthesis of 2,3-disubstituted indoles was developed by the domino aza-alkylation/intramolecular Michael reaction of 2-(tosylamino)phenyl α,β-unsaturated ketones with α-bromoacetophenones, followed by desulfonative dehydrogenation with DBU. The reaction afforded structurally diverse and highly functionalized 2,3-disubstituted indoles in moderate to excellent yields (up to 99%). The synthesis of 2,3-disubstituted indoles without desulfonation through DDQ-induced oxidative dehydrogenation was also achieved.