Stereoselective Synthesis of Biheterocycles Containing Indole and 5,6-Dihydropyridin-2(1H)-one or α-Methylene-β-butyrolactam Scaffolds

Indium-mediated allylation of N-tert-butanesulfinyl imines derived from indole-2 and 3-carbaldehydes 3 and 5 with allylic bromides 6, proceed with high diastereoselectivity. Homoallylic amide derivatives 13 and 14 are transformed into dihydropyridinones 15 and 16, upon successive desulfinylation, N-acylation with acryloyl chloride and ring-closing-metathesis. Desulfinylation of amine ester derivatives 17 and 18, obtained when ethyl 2-(bromomethyl)acrylate (6 b) is used as the allylating reagent, lead to the corresponding α-methylene-γ-butyrolactams 19 and 20, in modest yields.We thank the continuous financial support from the Spanish Ministerio de Economía y Competitividad (MINECO; project CTQ2016-81797-REDC, CTQ2017-85093-P), Ministerio de Ciencia, Innovación y Universidades (RED2018-102387-T, PID2019-107268GB-100), FEDER, the Generalitat Valenciana (IDIFEDER/2021/013, CIDEGENT/2020/058, APOTIP/2021/020), the University of Alicante (VIGROB-068), and the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique Algérienne; Direction de la Coopération et des Echanges Interuniversitaires; Programme de Formation Résidentielle à l’Étranger au titre de l’année universitaire 2019/2020: Programme National Exceptionnel (PNE)