Organocatalysed Asymmetric C-H Activation

T Akiyama et al (JACS, 2011, 133, (16), 6166) report an interesting reaction where organocatalysis has been used to achieve activation of a C-H bond via what is described as an overall internal redox process to generate tetrahydroquinolines in 9 of the 11 examples shown, with >90%ee from achiral starting material.

The reaction is outlined below using an organocatalyst.

Interestingly, they also report the use of chiral starting material (>98%ee) but this time using a lewis acid catalyst (Yb(OTf)₃) and found that the product had 85%ee, so considerable retention of stereochemistry.  This suggested that the stereoselectivity in the reaction does not reside entirely with the facial selectivity of the attack on the iminium species, but in fact is mostly controlled at the time of the hydride shift process.