ortho C−H Activation of Haloarenes and Anisole by an Electron-Rich Iridium(I) Complex:  Mechanism and Origin of Regio- and Chemoselectivity. An Experimental and Theoretical Study

Reaction of (PNP)Ir(COE) + PF 6 - ( 1 ) (PNP = 2,6-bis(di- tert -butylphosphinomethyl)pyridine; COE = cyclooctene) with benzene yields a stable unsaturated square pyramidal Ir(III) hydrido-aryl complex, 2, which undergoes arene exchange upon reaction with other arenes at 50 °C. Upon reaction of 1 with haloarenes (chlorobenzene and bromobenzene) and anisole at 50 °C, selective ortho C−H activation takes place. No C−halogen bond activation was observed, even in the case of the normally reactive bromobenzene and despite the steric hindrance imposed by the halo substituent. The ortho -activated complexes ( 8a, 9a, and 10a ) exhibited a higher barrier to arene exchange; that is, no exchange took place when heating at a temperature as high as 60 °C. These complexes were more stable, both thermodynamically and kinetically, than the corresponding meta - and para -isomers ( 8b, c, 9b, c, and 10b, c ). The observed selectivity is a result of coordination of the heteroatom to the metal center, which kinetically directs the metal to the ortho C−H bond and stabilizes the resulting complex thermodynamically. Upon reaction of complex 1 with fluorobenzene under the same conditions, no such selectivity was observed, due to low coordination ability of the fluorine substituent. Competition experiments showed that the ortho -activated complexes 8a, 9a, and 10a have similar kinetic stability, while thermodynamically the chloro and methoxy complexes 8a and 10a are more stable than the bromo complex 9a . Computational studies, using the mPW1K exchange−correlation functional and a variety of basis sets for PNP-based systems, provide mechanistic insight. The rate-determining step for the overall C−H activation process of benzene is COE dissociation to form a reactive 14 e complex. This is followed by formation of a η 2 C-C intermediate, which is converted into an η 2 C-H complex, both being important intermediates in the C−H activation process. In the case of chlorobenzene, bromobenzene, and anisole, η 1 -coordination via the heteroatom to the 14 e species followed by formation of the ortho η 2 C-H complex leads to selective activation. The unobserved C−halide activation process was shown computationally in the case of chlorobenzene to involve the same Cl-coordinated intermediate as in the C−H activation process, but it experiences a higher activation barrier. The ortho C−H activation product is also thermodynamically more stable than the C−Cl oxidative addition complex.