Catalyst-Counterion Controlled, Regioselective C-C Bond Cleavage in 1-Azabiphenylene: Synthesis of Selectively Substituted Benzoisoquinolines
Abstract
Catalytic C-C bond cleavage processes followed by further transformations are some of the most fascinating reactions in chemistry and valuable organic synthesis tools. Herein, we demonstrate that the regioselectivity of C-C bond cleavage in 1-azabiphenylene and its derivatives can be switched by using neutral or cationic transition metal catalysts.
The use of the former leads to selective distal C-C bond cleavage (with respect to the position of the nitrogen atom), whereas use of the latter leads to selective proximal bond cleavage. This process enables synthesis of a variety of complex heterocycles by regioselective C-C bond cleavage switched on demand.
Density functional theory calculations (SMD/M06/DGDZVP level of theory) show that the regioselectivity is a result of kinetically controlled oxidative addition into the C-C bond. In neutral complexes the transition states (TS) for distal cleavage have lower energy, in agreement with experiments.
For the cationic catalyst, the proximal TSs are stabilized presumably by relieving the Cl-N dipole dipole repulsion when the Rh-bound Cl is removed whereas the distal TSs remain largely unaffected.