Regioselective N- and C-Metalation of Neutral 2-Halogenobenzimidazole Derivatives

Neutral 2-chlorobenzimidazole (1) and its derivatives 8-chlorotheophylline (2) and 8-bromotheophylline (3) undergo at low temperature in THF an N-H polar oxidative addition reaction with Ni-0 to give exclusively the nickel(II) hydrido complexes trans-[4]-trans-[6] featuring an N-metalated five-membered azolato heterocycle. In spite of the reactive C-halogen bond, no C-metalation was observed in any of these reactions. At 45 degrees C, however, 2-chlorobenzimidazole (1) reacts in toluene/hexane in a polar oxidative addition of the C2-Cl bond to Ni-0 to yield a mixture of the complexes trans-[8] and trans-[9] both bearing a C-metalated benzimidazolato ligand. The related complex trans-[10] bearing a C-metalated azolato ligand is formed in the oxidative addition of 2-chlorocaffeine, featuring one alkylated ring nitrogen atom within the diaminoheterocycle to Ni-0.