Asymmetric Construction of 4 H-Pyrano[3,2- b]indoles via Cinchonine-Catalyzed 1,4-Addition of 2-Ylideneoxindole with Malononitrile.

A highly enantioselective [4 + 2] annulation of 2-ylideneoxindole with malononitrile has been accomplished by cinchonine catalysis under mild conditions. The corresponding enantiomerically enriched 4 H-pyrano[3,2- b]indoles were generated in moderate to high yields (up to 94%) with excellent enantioselectivities (up to 98% ee). To explain the stereoselectivity of the organocatalytic Michael-ammonization cascade, we also carried out the control experiments and proposed plausible transition-state models for the catalytic cycle based on the observed stereochemistry of the products. In addition, some of the products showed moderate antibacterial activity against S. aureus and S. epidermidis in vitro, which might be considered as a potential clue for the discovery of new antimicrobial agents.