Enantioselective Cascade Michael/Hemiaminal Formation of α,β-Unsaturated Iminoindoles with Aldehydes Using a Chiral Aminomethylpyrrolidine Catalyst Bearing a SO<sub>2</sub>C<sub>6</sub>F<sub>5</sub> Group as a Strongly Electron Withdrawing Arylsulfonyl Group
Katsuhiko Moriyama, Yukari Oka
Abstract
An enantioselective cascade Michael/hemiaminal formation of α,β-unsaturated iminoindoles with aldehydes using a chiral aminomethylpyrrolidine catalyst bearing a SO2C6F5 group as strongly electron withdrawing arylsulfonyl group was developed to furnish anti-2-hydroxy-hydro-1H-pyrido[2,3-b]indole (anti-α-carbolinol) derivatives in high yields with high stereoselectivity. DFT calculation studies indicate that multiple hydrogen-bonding interactions between the enamine species and the α,β-unsaturated iminoindole form a favored transition state (TSmajor) in the Michael reaction step, thereby inducing high enantioselectivity in the reaction. Furthermore, various transformations of the reaction product, namely, C–O bond formation, oxidation, reduction, and C–C bond formation of the anti-α-carbolinol derivatives, gave a wide range of hydro-1H-pyrido[2,3-b]indole derivatives in high yields.