Asymmetric synthesis of 3-substituted indole derivatives containing tetrahydrothiophene via cascade sulfa-Michael/Michael additions catalyzed by a chiral squaramide catalyst

The organocatalyzed enantioselective cascade sulfa-Michael/Michael addition reaction of (E)-3-mercapto-2-butenoic acid esters to (E)-3-aryl-2-(indol-3-ylcarbonyl)acrylonitriles has been developed. This process was promoted by a chiral squaramide catalyst to afford chiral 3-substituted indole derivatives containing tetrahydrothiophene with three contiguous stereocenters in excellent diastereoselectivities (up to >20:1 dr) with moderate to good yields and enantioselectivities (up to 93%, 89% ee).