Claire L. McMullin

Accurate modelling of Pd(0) + PhX oxidative addition kinetics

We have used dispersion-corrected DFT (DFT-D) together with solvation to examine possible mechanisms for reaction of PhX (X = Cl, Br, I) with Pd(P(t)Bu(3))(2) and compare our results to recently published kinetic data (F. Barrios-Landeros, B. P. Carrow and J. F. Hartwig, J. Am. Chem. Soc., 2009, 131, 8141-8154). The calculated activation free energies agree near-quantitatively with experimentally observed rate constants.

Reaction of CuI with Dialkyl Peroxides: CuII-Alkoxides, Alkoxy Radicals, and Catalytic C–H Etherification

Kinetic analysis of the reaction of the copper(I) β-diketiminate [Cl(2)NN]Cu ([Cu(I)]) with (t)BuOO(t)Bu to give [Cu(II)]-O(t)Bu (1) reveals first-order behavior in each component implicating the formation of free (t)BuO(•) radicals. Added pyridine mildly inhibits this reaction indicating competition between (t)BuOO(t)Bu and py for coordination at [Cu(I)] prior to peroxide activation. Reaction of [Cu(I)] with dicumyl peroxide leads to [Cu(II)]-OCMe(2)Ph (3) and acetophenone suggesting the intermediacy of the PhMe(2)CO(•) radical. Computational methods provide insight into the activation of (t)BuOO(t)Bu at [Cu(I)]. The novel peroxide adduct [Cu(I)]((t)BuOO(t)Bu) (4) and the square planar [Cu(III)](O(t)Bu)(2) (5) were identified, each unstable toward loss of the (t)BuO(•) radical. Facile generation of the (t)BuO(•) radical is harnessed in the catalytic C-H etherification of cyclohexane with (t)BuOO(t)Bu at rt employing [Cu(I)] (5 mol %) to give the ether Cy-O(t)Bu in 60% yield.

C-H Functionalization Reactivity of a Nickel-Imide

We report bifunctional reactivity of the β-diketiminato Ni(III)-imide [Me(3)NN]Ni═NAd (1), which undergoes H-atom abstraction (HAA) reactions with benzylic substrates R-H (indane, ethylbenzene, toluene). Nickel-imide 1 competes with the nickel-amide HAA product [Me(3)NN]Ni-NHAd (2) for the resulting hydrocarbyl radical R(•) to give the nickel-amide [Me(3)NN]Ni-N(CHMePh)Ad (3) (R-H = ethylbenzene) or aminoalkyl tautomer [Me(3)NN]Ni(η(2)-CH(Ph)NHAd) (4) (R-H = toluene). A significant amount of functionalized amine R-NHAd is observed in the reaction of 1 with indane along with the dinickel imide {[Me(3)NN]Ni}(2)(μ-NAd) (5). Kinetic and DFT analyses point to rate-limiting HAA from R-H by 1 to give R(•), which may add to either imide 1 or amide 2, each featuring significant N-based radical character. Thus, these studies illustrate a fundamental competition possible in C-H amination systems that proceed via a HAA/radical rebound mechanism.

Experimental and DFT Studies Explain Solvent Control of C–H Activation and Product Selectivity in the Rh(III)-Catalyzed Formation of Neutral and Cationic Heterocycles

A range of novel heterocyclic cations have been synthesized by the Rh(III)-catalyzed oxidative C-N and C-C coupling of 1-phenylpyrazole, 2-phenylpyridine, and 2-vinylpyridine with alkynes (4-octyne and diphenylacetylene). The reactions proceed via initial C-H activation, alkyne insertion, and reductive coupling, and all three of these steps are sensitive to the substrates involved and the reaction conditions. Density functional theory (DFT) calculations show that C-H activation can proceed via a heteroatom-directed process that involves displacement of acetate by the neutral substrate to form charged intermediates. This step (which leads to cationic C-N coupled products) is therefore favored by more polar solvents. An alternative non-directed C-H activation is also possible that does not involve acetate displacement and so becomes favored in low polarity solvents, leading to C-C coupled products. Alkyne insertion is generally more favorable for diphenylacetylene over 4-octyne, but the reverse is true of the reductive coupling step. The diphenylacetylene moiety can also stabilize unsaturated seven-membered rhodacycle intermediates through extra interaction with one of the Ph substituents. With 1-phenylpyrazole this effect is sufficient to suppress the final C-N reductive coupling. A comparison of a series of seven-membered rhodacycles indicates the barrier to coupling is highly sensitive to the two groups involved and follows the trend C-N(+) > C-N > C-C (i.e., involving the formation of cationic C-N, neutral C-N, and neutral C-C coupled products, respectively).

Combined experimental and computational investigations of rhodium- and ruthenium-catalyzed C–H functionalization of pyrazoles with alkynes

Detailed experimental and computational studies are reported on the mechanism of the coupling of alkynes with 3-arylpyrazoles at [Rh(MeCN)3Cp*][PF6]2 and [RuCl2(p-cymene)]2 catalysts. Density functional theory (DFT) calculations indicate a mechanism involving sequential N-H and C-H bond activation, HOAc/alkyne exchange, migratory insertion, and C-N reductive coupling. For rhodium, C-H bond activation is a two-step process comprising κ(2)-κ(1) displacement of acetate to give an agostic intermediate which then undergoes C-H bond cleavage via proton transfer to acetate. For the reaction of 3-phenyl-5-methylpyrazole with 4-octyne k(H)/k(D) = 2.7 ± 0.5 indicating that C-H bond cleavage is rate limiting in this case. However, H/D exchange studies, both with and without added alkyne, suggest that the migratory insertion transition state is close in energy to that for C-H bond cleavage. In order to model this result correctly, the DFT calculations must employ the full experimental system and include a treatment of dispersion effects. A significantly higher overall barrier to catalysis is computed at {Ru(p-cymene)} for which the rate-limiting process remains C-H activation. However, this is now a one-step process corresponding to the κ(2)-κ(1) displacement of acetate and so is still consistent with the lack of a significant experimental isotope effect (k(H)/k(D) = 1.1 ± 0.2).

Organometallic reactivity: the role of metal–ligand bond energies from a computational perspective

The association and dissociation of ligands plays a vital role in determining the reactivity of organometallic catalysts. Computational studies with density functional theory often fail to reproduce experimental metal-ligand bond energies, but recently functionals which better capture dispersion effects have been developed. Here we explore their application and discuss future challenges for computational studies of organometallic catalysis.

Copper(II) Anilides in sp3 C-H Amination

We report a series of novel β-diketiminato copper(II) anilides [Cl2NN]Cu-NHAr that participate in C-H amination. Reaction of H2NAr (Ar = 2,4,6-Cl3C6H2 (Ar(Cl3)), 3,5-(CF3)2C6H3 (Ar(F6)), or 2-py) with the copper(II) t-butoxide complex [Cl2NN]Cu-(t)OBu yields the corresponding copper(II) anilides [Cl2NN]Cu-NHAr. X-ray diffraction of these species reveal three different bonding modes for the anilido moiety: κ(1)-N in the trigonal [Cl2NN]Cu-NHAr(Cl3) to dinuclear bridging in {[Cl2NN]Cu}2(μ-NHAr(F6))2 and κ(2)-N,N in the square planar [Cl2NN]Cu(κ(2)-NH-2-py). Magnetic data reveal a weak antiferromagnetic interaction through a π-stacking arrangement of [Cl2NN]Cu-NHAr(Cl3); solution EPR data are consistent with monomeric species. Reaction of [Cl2NN]Cu-NHAr with hydrocarbons R-H (R-H = ethylbenzene and cyclohexane) reveals inefficient stoichiometric C-H amination with these copper(II) anilides. More rapid C-H amination takes place, however, when (t)BuOO(t)Bu is used, which allows for HAA of R-H to occur from the (t)BuO(•) radical generated by reaction of [Cl2NN]Cu and (t)BuOO(t)Bu. The principal role of these copper(II) anilides [Cl2NN]Cu-NHAr is to capture the radical R(•) generated from HAA by (t)BuO(•) to give functionalized aniline R-NHAr, resulting in a novel amino variant of the Kharasch-Sosnovsky reaction.

Dehydrogenative Boron Homocoupling of an Amine‐Borane

The dehydrogenative coupling of amine-boranes as catalyzed by transition-metal fragments offers the potential for controlled hydrogen release and the formation of oligomeric and polymeric materials in which head-to-tail coupling yields products with B N bonds that are isoelectronic with technologically pervasive polyolefins. Because of this, the area has received considerable attention recently and there are now a wide range of catalysts available, which operate using inner-sphereor outer-sphere-type mechanisms, that dehydrogenatively couple amine-boranes of the general formula H3B·NRR’H (R, R’= H, alkyl) to give monomeric, cyclic, or polymeric amino-borane materials based on H2B=NRR’. By contrast, the homocoupling of amine-boranes to form welldefined products with B B single bonds has not been reported, although dehydrogenation of H3B·NH3 by [Pd(NCMe)4][BF4] has been reported to form insoluble polymeric materials with B B bonds. This preference for heterocoupling likely stems from the fact that B-H/N-H activation of amine-boranes gives amino-boranes that are well set up for further oligomerization through the formation of dative B N bonds, a process that is also driven thermodynamically by the differences in relative s-bond strengths between B B (70 kcalmol ) and B N (107 kcal mol ) single bonds. Well-defined homocoupling of boranes, as mediated by transition metals, is essentially limited to B B bond formation in polyhedral boranes, for example pentaborane(9) (A), guanidine bases (B), and most recently the homocoupling of HBCat and related derivatives to give the corresponding diboranes (C) (Scheme 1). By contrast, the homocoupling of phosphines or silanes is well established. 14] The homocoupling of boranes requires the B-H activation of two boranes at a metal center; we, and others, have recently reported on B-H activation at group 9 metal centers in both amineand amino-boranes. In particular, H3B·NMe3 undergoes B-H activation at {Rh(PR3)n} + fragments to give bimetallic hydrido-boryl products (n = 1, R3 = Cy3), [17] or in the presence of the alkene tert-butylethene (TBE, n = 2, R3 = iBu2tBu) catalytic hydroboration occurs to afford Me3N·BH2CH2CH2tBu, I. [18] The suggested mechanism for this process involves reversible B-H activation to give a hydrido-boryl complex, alkene insertion, and subsequent reductive elimination of I. Homocoupling of H3B·NMe3 was not observed, possibly because the approach of the second equivalent of H3B·NMe3 to the metal is hindered. However, the Ir pincer system Ir(tBuPOCOPtBu)(H)2 [tBuPOCOPtBu = kP,C,P-1,3-(OPtBu2)2C6H3] catalyzes the dehydropolymerization of H3B·NMeH2, for which polymer growth kinetics suggest a coordination insertion mechanism consistent with the activation of two amine-boranes at the metal center before B N bond formation. Taking clues from this and using a related pincer system based on the {Rh(Xantphos)} fragment, we now report that H3B·NMe3 undergoes stoichiometric homo-dehydrocoupling to form the diborane(4) H4B2·2 NMe3 II (Scheme 1D), a compound previously synthesized from the combination of NMe3 with B3H7L (L = THF, SMe2). [20] Addition of H3B·NMe3 to the precursor [Rh(k 2 P,PXantphos)(NBD)][BAr4] [21] under a H2 atmosphere resulted in rapid hydrogenation of the diene and coordination of the amine-borane to the resulting Rh dihydride to give Scheme 1. Homocoupling to form B B bonds.

Computed ligand effects on the oxidative addition of phenyl halides to phosphine supported palladium(0) catalysts

The manifold of reaction pathways for the oxidative addition of phenyl bromide and phenyl chloride substrates to phosphine-modified palladium(0) complexes has been investigated with dispersion-corrected density functional theory (B3LYP-D2) for a range of synthetically relevant ligands, permitting the evaluation of ligand, substrate and method effects on calculated predictions. Bulky and electron-rich ligands P(t)Bu3 and SPhos can access low-coordinate complexes more easily, facilitating formation of the catalytically active species throughout the cycle. While the bisphosphine oxidative addition step is reasonably facile for the smaller PCy3 and PPh3 ligands, the dissociation of these ligands to generate reactive palladium complexes becomes more important and the catalyst is more likely to become trapped in unreactive intermediates. This study demonstrates the feasibility of exploring the catalytic manifold for synthetically relevant ligands with computational chemistry, but also highlights the remaining challenges.

Combined experimental and computational investigations of rhodium-catalysed C - H functionalisation of pyrazoles with alkenes.

Detailed experimental and computational studies have been carried out on the oxidative coupling of the alkenes C2H3Y (Y=CO2Me (a), Ph (b), C(O)Me (c)) with 3-aryl-5-R-pyrazoles (R=Me (1 a), Ph (1 b), CF3 (1 c)) using a [Rh(MeCN)3Cp*][PF6]2/Cu(OAc)2⋅H2O catalyst system. In the reaction of methyl acrylate with 1 a, up to five products (2 aa–6 aa) were formed, including the trans monovinyl product, either complexed within a novel CuI dimer (2 aa) or as the free species (3 aa), and a divinyl species (6 aa); both 3 aa and 6 aa underwent cyclisation by an aza-Michael reaction to give fused heterocycles 4 aa and 5 aa, respectively. With styrene, only trans mono- and divinylation products were observed, whereas with methyl vinyl ketone, a stronger Michael acceptor, only cyclised oxidative coupling products were formed. Density functional theory calculations were performed to characterise the different migratory insertion and β-H transfer steps implicated in the reactions of 1 a with methyl acrylate and styrene. The calculations showed a clear kinetic preference for 2,1-insertion and the formation of trans vinyl products, consistent with the experimental results.