Enantioselective reductive multicomponent coupling reactions between isatins and aldehydesElectronic supplementary information (ESI) available: Experimental procedures and characterizations of compounds. CCDC 1055582. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5sc02170g

A metal-free stereoselective reductive coupling reaction between isatins and aldehydes is reported. The reaction relies on commercial diethyl phosphite (∼€70 kg −1 ) as the stoichiometric reductant. Base-catalyzed Pudovik addition and phosphonate/phosphate rearrangement achieved polarity inversion on the isatin, and the derived carbanions were trapped by aldehydes with subsequent dialkoxyphosphinyl migration. Chiral iminophosphoranes were used as basic catalysts to achieve high diastereo- and enantioselectivities with excellent yields. A reductive coupling of two different carbonyls via a polar two-electron reaction mechanism was developed and the stereochemical outcome of this multicomponent process is precisely controlled by a chiral triaminoiminophosphorane.