Chiral phosphoric acid catalyzed enantioselective addition of thiols to in situ generated ketimines: Synthesis of N,S-ketals

The chiral Bronsted acid catalyzed enantioselective 1,2-addition of thiols to in situ generated ketimines, derived from 3-hydroxyisoindolinones, has been studied. The protocol provides a variety of isoindolinone-derived N,S-ketals in up to 98% yield and up to 99% enantioselectivity. The products have been converted to a known non-nucleoside HIV-1 reverse transcriptase inhibitor and a 1,3-thiazine derivative. (C) 2016 Elsevier Ltd. All rights reserved.