Introducing the Chiral Transient Directing Group Strategy to Rhodium(III)-Catalyzed Asymmetric C-H Activation

Abstract

The chiral transient directing group (TDG) strategy has been successfully introduced to the rhodium(III)-catalyzed asymmetric C-H activation. In the presence of a catalytic amount of a chiral amine and an achiral rhodium catalyst, various chiral phthalides were synthesized from simple aldehydes with high chemoselectivity, regioselectivity, and enantioselectivity (53 examples, up to 73 % yield and >99 % ee). It is noteworthy that the chiral induction model is different from the previously reported chiral TDG system using amino acid derivatives and palladium salts. The imino group generated in situ from chiral amine and aldehyde acts as the monodentate TDG to promote the C-H activation, stereoselectively generating the chiral rhodacycle bearing a chiral metal center. Moreover, the stereogenic center of the product is created and stereocontrolled during the Grignard-type addition of the C-Rh bond to aldehyde, rather than during the C-H activation step.

Keywords: C−H activation; asymmetric catalysis; chiral transient directing group; phthalide; rhodium(III).