Enantioselective intramolecular tandem cyclization of o-alkynylbenzamides: generation of enantioenriched CF3-containing spiro-isoindolinone-indoles

Abstract

Enantioselective intramolecular tandem cyclization of dielectrophile–dinucleophile assembled o-alkynylbenzamides was realized using a chiral phosphoric acid as the catalyst. A large variety of biologically important spiro-isoindolinone-indoles were achieved in moderate to good enantioselectivities (up to 93% ee). The absolute configuration of one product was assigned by an X-ray crystal structure analysis and a plausible reaction mechanism was proposed. Afterward, scale-up synthesis and transformations of one product were conducted successfully.