Towards Rational Understandings of α-C–H Functionalization: Energetic Studies of Representative Tertiary Amines

Functionalization of α-C–H bonds of tertiary amines to build various α-C–X bonds has become a mainstream in synthetic chemistry. However, due to lack of fundamental knowledge on α-C–H bond strength, rational exploration of new synthetic methodologies remains a far-reaching anticipation. Herein, we report a unique hydricity-based approach to establish the first integrated energetic scale covering both the homolytic and heterolytic energies of α-C–H bonds for 45 representative tertiary amines and their radical cations. As showcased from the studies on tetrahydroisoquinolines by virtue of the thermodynamic criteria, the feasibility and mechanisms of their oxidation were deduced, and indeed, were found to correspond well with experimental observations. This energetic scale actually provides a good example among the α-C–H categories to relate the bond thermodynamics with mechanisms/reactivity of their α-C–H transformation, and hence, may be referenced for analyzing similar structure-property problems for a wide variety of substrates.