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

Abstract

Reaction of (PNP)Ir(COE)+PF6 - (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 14e complex. This is followed by formation of a η2 C-C intermediate, which is converted into an η2 C-H complex, both being important intermediates in the C−H activation process. In the case of chlorobenzene, bromobenzene, and anisole, η1-coordination via the heteroatom to the 14e species followed by formation of the ortho η2 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.

Experimental and Computational Studies on the Iridium Activation of Aliphatic and Aromatic CH Bonds of Alkyl Aryl Ethers and Related Molecules

“…In accord with previous studies, [12] a fast equilibrium between the three C À H coordination isomers must be attained and since the ortho-species 23 is somewhat more stable (hence it is the most populated one) the observed reactivity starts at this point.…”

“…[12] In our system, the CÀO bond cleavage is accompanied by the formation of a new CÀC bond, which gives rise in appropriate cases to hydride alkylidene and hydride alkene iridium tautomers that exist in equilibrium. This facet of the chemistry of the alkyl aryl ethers investigated here will be dealt with in the following paper in this issue, [11] taking advantage of the observation of such a reactivity in the reactions of 1 with 2,6-methylanisole and related molecules.…”

“…Yield: 42 % (0.040 g). 151.6,150.7,143.8,143.2,142.7 (C qpz );127.8,125.1,114.5,114.1 (CH ar );115.0 (NCMe);108.3,107.6,106.6 (CH pz );14.4,12.9,12.8,12.8,12.6,12.0 (Me pz ); 3.8 (NCMe); À0.6 ppm ( 1 JA C H T U N G T R E N N U N G (C,H) = 128 Hz; Ir-CH 2 ); elemental analysis calcd (%) for C 24 H 31 BN 7 OIr·0.5 CH 2 Cl 2 : C 43.3, H 4.7, N 14.4; found: C 43.5, H 4.8, N 13.9. 8,150.8,150.5,145.2,144.2,143.0 (C qpz );129.1,129.0,127.0,117.4 (CH ar );107.5,106.4,105.1 (CH pz );15.8,15.3,13.0,12.7,12.5,12.4 (Me pz H 5.2, N 11.1; found: C 40.9, H 5.0, N 10.7.…”

“…For the alternative possibility, namely, initial CÀH bond activation of the methoxy unit (Scheme 6a), oxygen coordination is a prerequisite. As already noted, Martin, Milstein, and co-workers performed experimental and computational studies [12] on the aromatic C À H bond activation of benzene, anisole, and other aromatic molecules.…”

Olefin Substitution in (silox)3M(olefin) (silox = tBu3SiO; M = Nb, Ta): The Role of Density of States in Second vs Third Row Transition Metal Reactivity

“…37 The structural differences can be traced to the relatively lower lying 5d z 2 orbital, which is occupied as the geometry approaches square planar. In terms of reactivity studies, Ozerov, 38 Smith, 39 and Milstein 40 have noted a greater propensity for ArX bond activation in d 8 Rh complexes relative to their Ir congeners, which tend to exhibit ArH bond activation chemistry. It is plausible that the relatively higher lying 4d z 2 orbital of Rh acts in a nucleophilic fashion to activate aryl-halide bonds via L 2 -YRh(ArX), whereas the 5d z 2 orbital of Ir is quite low in energy, and the electrophilic activation of aryl-hydrogen bonds takes precedence via L 2 YIr(ArH).…”