Laura L. Santos

C−H Bond Activation Reactions of Ethers That Generate Iridium Carbenes

Two important objectives in organometallic chemistry are to understand C-H bond activation reactions mediated by transition metal compounds and then to develop efficient ways of functionalizing the resulting products. A particularly ambitious goal is the generation of metal carbenes from simple organic molecules; the synthetic chemist can then take advantage of the almost unlimited reactivity of this metal-organic functionality. This goal remains very difficult indeed with saturated hydrocarbons, but it is considerably more facile for molecules that possess a heteroatom (such as ethers), because coordination of the heteroatom to the metal renders the ensuing C-H activation an intramolecular reaction. In this Account, we focus on the activation reaction of different types of unstrained ethers, both aliphatic and hemiaromatic, by (mostly) iridium compounds. We emphasize our recent results with the Tp(Me2)Ir(C(6)H(5))(2)(N(2)) (1.N(2)) complex (where Tp(Me2) denotes hydrotris(3,5-dimethylpyrazolyl)borate). Most of the reactivity observed with this system, and with related electronically unsaturated iridium species, starts with a C-H activation reaction, which is then followed by reversible alpha-hydrogen elimination. An alpha-C-H bond is, in every instance, broken first; when there is a choice, cleavage of the stronger terminal C(sp(3))-H bonds is always preferred over the weaker internal C(sp(3))-H (methylene) bonds of the ether. Nevertheless, competitive reactions of the unsaturated [Tp(Me2)Ir(C(6)H(5))(2)] iridium intermediate with ethers that contain C(sp(3))-H and C(sp(2))-H bonds are also discussed. We present theoretical evidence for a sigma-complex-assisted metathesis mechanism (sigma-CAM), although for other systems oxidative addition and reductive elimination events can be effective reaction pathways. We also show that additional unusual chemical transformations may occur, depending on the nature of the ether, and can result in C-O and C-C bond-breaking and bond-forming reactions, leading to the formation of more elaborate molecules. Although the possibility of extending these results to saturated hydrocarbons appears to be limited for this iridium system, the findings described in this Account are of fundamental importance for various facets of C-H bond activation chemistry, and with suitable modifications of the ancillary ligands, they could be even broader in scope. We further discuss experimental and theoretical studies on unusual alkene-to-alkylidene equilibria for some of the products obtained in the reactions of iridium complex 1.N(2) with alkyl aryl ethers. The rearrangement involves reversible alpha- and beta-hydrogen eliminations, with a rate-determining metal inversion step (supported by theoretical calculations); the alkylidene is always favored thermodynamically over the alkene. This startling result contrasts with the energetically unfavorable isomerization of free ethene to ethylidene (by about 80 kcal mol(-1)), showing that the tautomerism equilibrium can be directed toward one product or the other by a judicious choice of the transition metal complex.

C–H bond activation reactions by TpMe2Ir(III) centres. Generation of Fischer-type carbenes and development of a catalytic system for H/D exchange

The unsaturated [TpMe2Ir(C6H5)2] fragment, readily generated from [TpMe2Ir(C6H5)2(N2)], or from [TpMe2Ir(C2H4)2] and C6H6, is able to induce the regioselective cleavage of two sp3 C–H bonds of anisole, with formation of a Fischer-type carbene, 1. The process involves additionally ortho-metallation of the anisole aromatic ring, hence three C–H bonds are sequentially broken, the last one in the course of an α-H elimination reaction. Phenetole (ethyl phenyl ether) gives an analogous product, 3, despite the possibility of competitive α- or β-H eliminations in the last step. For C6H5NMe2, two hydride-carbenes, 5a and 5b, are produced. In the latter, the aniline phenyl ring is also metallated, but the former contains a C6H5 aryl group and a C6H5N(Me)CH carbene ligand. The same Ir(III) fragment, viz. [TpMe2Ir(C6H5)2], alternatively generated from C6H6 and [TpMe2Ir(η4-CH2C(Me)C(Me)CH2)], accomplishes the efficient, catalytic H/D exchange between C6D6 (used as the deuterium source) and a variety of organic and organometallic molecules that contain C–H bonds of different nature.

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

Reaction of the Ir(III) complex [(Tp(Me2))Ir(C(6)H(5))(2)(N(2))] (1N(2)) with ortho-cresol (2-methylphenol) occurs with cleavage of the O-H and two C(sp(3))-H bonds of the phenol and formation of the electrophilic hydride alkylidene derivative [(Tp(Me2))Ir(H){=C(H)C(6)H(4)-o-O}] (2). The analogous reaction of 2-ethylphenol gives a related product 3. Both 2 and 3 have been shown to be identical to the minor, unidentified products of the already reported reactions of 1 with anisole and phenetole, respectively. Thus, in addition to the route that leads to the known heteroatom-stabilized hydride carbene [(Tp(Me2))Ir(H){=C(H)OC(6)H(4)-o-}] (B), anisole can react with 1 with cleavage of the O-CH(3) bond and formation of a new carbon-carbon bond. In contrast, only C-H bond-activation products with structures akin to B result from 1N(2) and 3,5-dimethylanisole (complex 8) or 4-fluoroanisole (9). Using anisole as a model, a computational study of the triple C-H bond activation (two aliphatic C-H bonds plus an ortho-metalation reaction) that is responsible for the formation of these heteroatom-stabilized hydride carbenes has been undertaken.

Synthetic, mechanistic, and theoretical studies on the generation of iridium hydride alkylidene and iridium hydride alkene isomers.

Experimental and theoretical studies on equilibria between iridium hydride alkylidene structures, [(Tp(Me2))Ir(H){=C(CH(2)R)ArO}] (Tp(Me2) = hydrotris(3,5-dimethylpyrazolyl)borate; R = H, Me; Ar = substituted C(6)H(4) group), and their corresponding hydride olefin isomers, [(Tp(Me2))Ir(H){R(H)C=C(H)OAr}], have been carried out. Compounds of these types are obtained either by reaction of the unsaturated fragment [(Tp(Me2))Ir(C(6)H(5))(2)] with o-C(6)H(4)(OH)CH(2)R, or with the substituted anisoles 2,6-Me(2)C(6)H(3)OMe, 2,4,6-Me(3)C(6)H(2)OMe, and 4-Br-2,6-Me(2)C(6)H(2)OMe. The reactions with the substituted anisoles require not only multiple C-H bond activation but also cleavage of the Me-OAr bond and the reversible formation of a C-C bond (as revealed by (13)C labeling studies). Equilibria between the two tautomeric structures of these complexes were achieved by prolonged heating at temperatures between 100 and 140 degrees C, with interconversion of isomeric complexes requiring inversion of the metal configuration, as well as the expected migratory insertion and hydrogen-elimination reactions. This proposal is supported by a detailed computational exploration of the mechanism at the quantum mechanics (QM) level in the real system. For all compounds investigated, the equilibria favor the alkylidene structure over the olefinic isomer by a factor of between approximately 1 and 25. Calculations demonstrate that the main reason for this preference is the strong Ir-carbene interactions in the carbene isomers, rather than steric destabilization of the olefinic tautomers.

Iridium solutes effect C-H bond activation and C-C bond forming reactions of C6H6-MeOCH2CH2OMe solvent mixtures

The in situ generated [Tp(Me2)Ir(C(6)H(5))(2)] fragment induces both aromatic and aliphatic C-H bond activation reactions, along with C-C bond formation, when heated with benzene and 1,2-dimethoxyethane.

Reaction of [TpRh(C2H4)2] with Dimethyl Acetylenedicarboxylate: Identification of Intermediates of the [2+2+2] Alkyne and Alkyne–Ethylene Cyclo(co)trimerizations

The reaction between the bis(ethylene) complex [TpRh(C2 H4 )2 ], 1, (Tp=hydrotris(pyrazolyl)borate), and dimethyl acetylenedicarboxylate (DMAD) has been studied under different experimental conditions. A mixture of products was formed, in which TpRh(I) species were prevalent, whereas the presence of trapping agents, like water or acetonitrile, allowed for the stabilization and isolation of octahedral TpRh(III) compounds. An excess of DMAD gave rise to a small amount of the [2+2+2] cyclotrimerization product hexamethyl mellitate (6). Although no catalytic application of 1 was achieved, mechanistic insights shed light on the formation of stable rhodium species representing the resting state of the catalytic cycle of rhodium-mediated [2+2+2] cyclo(co)trimerization reactions. Metallacyclopentene intermediate species, generated from the activation of one alkyne and one ethylene molecule from 1, and metallacyclopentadiene species, formed by oxidative coupling of two alkynes to the rhodium centre, are crucial steps in the pathways leading to the final organometallic and organic products.

Chlorido[1-(2-oxidophen­yl)ethyl­idene][tris­(3,5-dimethyl­pyrazol-1-yl)hydro­borato]iridium(III) chloro­form monosolvate

In the title compound, [Ir(C15H22BN6)(C8H7O)Cl]·CHCl3, the Ir atom is formally trivalent and is coordinated in a slightly distorted octahedral geometry by three facial N atoms, one C atom, one O atom and one Cl atom. The Ir=Ccarbene bond is strong and short and exerts a notable effect on the trans-Ir—N bond, which is about 0.10 Å longer than the two other Ir—N bonds. The chloroform solvent molecule is anchored via a weak C—H⋯Cl hydrogen bond to the Cl atom of the Ir complex molecule. In the crystal, the constituents adopt a layer-like arrangement parallel to (010) and are held together by weak intermolecular C—H⋯Cl hydrogen bonds, as well as weak Cl⋯Cl [3.498 (2) Å] and Cl⋯π [3.360 (4) Å] interactions. A weak intramolecular C—H⋯O hydrogen bond is also observed.

(Butane-1,4-di­yl)(trimethyl­phosphane-κP)[tris­(3,5-dimethyl­pyrazol-1-yl-κN2)hydro­borato]iridium(III)

In the mononuclear title iridium(III) complex, [Ir(C4H8)(C15H22BN6)(C3H9P)], which is based on the [tris(3,5-dimethylpyrazol-1-yl)hydroborato]iridium moiety, Ir[TpMe2], the IrIII atom is coordinated by a chelating butane-1,4-diyl fragment and a trimethylphosphane ligand in a modestly distorted octahedral coordination environment formed by three facial N, two C and one P atom. The iridium–butane-1,4-diyl ring has an envelope conformation. This ring is disordered because alternately the second or the third C atom of the butane-1,4-diyl fragment function as an envelope flap atom (the occupancy ratio is 1:1). In the crystal, molecules are organized into densely packed columns extending along [101]. Coherence between the molecules is essentially based on van der Waals interactions.