B(C6 F5 )3 /Chiral Phosphoric Acid Catalyzed Ketimine-Ene Reaction of 2-Aryl-3H-indol-3-ones and α-Methylstyrenes.

Abstract

The enantioselective ketimine-ene reaction is one of the most challenging stereocontrolled reaction types in organic synthesis. In this work, catalytic enantioselective ketimine-ene reactions of 2-aryl-3H-indol-3-ones with α-methylstyrenes were achieved by utilizing a B(C6 F5 )3 /chiral phosphoric acid (CPA) catalyst. These ketimine-ene reactions proceed well with low catalyst loading (B(C6 F5 )3 /CPA=2 mol %/2 mol %) under mild conditions, providing rapid and facile access to a series of functionalized 2-allyl-indolin-3-ones with very good reactivity (up to 99 % yield) and excellent enantioselectivity (up to 99 % ee). Theoretical calculations reveal that enhancement of the acidity of the chiral phosphoric acid by B(C6 F5 )3 significantly reduces the activation free energy barrier. Furthermore, collective favorable hydrogen-bonding interactions, especially the enhanced N-H⋅⋅⋅O hydrogen-bonding interaction, differentiates the free energy of the transition states of CPA and B(C6 F5 )3 /CPA, thereby inducing the improvement of stereoselectivity.