Mechanism of C[bond]H bond activation/C[bond]C bond formation reaction between diazo compound and alkane catalyzed by dirhodium tetracarboxylate

The B3LYP density functional studies on the dirhodium tetracarboxylate-catalyzed C-H bond activation/C-C bond formation reaction of a diazo compound with an alkane revealed the energetics and the geometry of important intermediates and transition states in the catalytic cycle. The reaction is initiated by complexation between the rhodium catalyst and the diazo compound. Driven by the back-donation from the Rh 4d(xz) orbital to the C[bond]N sigma*-orbital, nitrogen extrusion takes place to afford a rhodium[bond]carbene complex. The carbene carbon of the complex is strongly electrophilic because of its vacant 2p orbital. The C[bond]H activation/C[bond]C formation proceeds in a single step through a three-centered hydride transfer-like transition state with a small activation energy. Only one of the two rhodium atoms works as a carbene binding site throughout the reaction, and the other rhodium atom assists the C[bond]H insertion reaction. The second Rh atom acts as a mobile ligand for the first one to enhance the electrophilicity of the carbene moiety and to facilitate the cleavage of the rhodium[bond]carbon bond. The calculations reproduce experimental data including the activation enthalpy of the nitrogen extrusion, the kinetic isotope effect of the C[bond]H insertion, and the reactivity order of the C[bond]H bond.     

Carbon [bond] hydrogen bond activation by titanium imido complexes. Computational evidence for the role of alkane adducts in selective C [bond] H activation

This paper reports calculations that probe the role of R (hydrocarbon) and R' (ligand substituent) effects on the reaction coordinate for C [bond] H activation: Ti(OR')(2)(=NR') + RH --> adduct --> transition state --> (OR')(2)Ti(N(H)R')(R). Compounds with R = H, Me, Et, Vy, cPr, Ph, Cy, Bz, and cubyl are studied using quantum (R' = H, SiH(3), SiMe(3)) and classical (R' = Si(t)Bu(3)) techniques. Calculated geometries are in excellent agreement with data for experimental models. There is little variability in the calculated molecular structure of the reactants, products, and most interestingly, transition states as R and R' are changed. Structural flexibility is greatest in the adducts Ti(OR')(2)(=NR')...HR. Despite the small structural changes observed for Ti(OR')(2)(double bond] NR') with different R', significant changes are manifested in calculated electronic properties (the Mulliken charge on Ti becomes more positive and the Ti [double bond] N bond order decreases with larger R'), changes that should facilitate C [bond] H activation. Substantial steric modification of the alkane complex is expected from R [bond] R' interactions, given the magnitude of Delta G(add) and the conformational flexibility of the adduct. Molecular mechanics simulations of Ti(OSi(t)Bu(3))(2)([double bond] NSi(t)Bu(3))...isopentane adducts yield an energy ordering as a function of the rank of the C [bond] H bond coordinated to Ti that is consistent with experimental selectivity patterns. Calculated elimination barriers compare very favorably with experiment; larger SiH(3) and TMS ligand substituents generally yield better agreement with experiment, evidence that the modeling of the major contributions to the elimination barrier (N [bond] H and C [bond] H bond making) is ostensibly correct. Calculations indicate that weakening the C [bond] H bond of the hydrocarbon yields a more strongly bound adduct. Combining the different conclusions, the present computational research points to the adduct, specifically the structure and energetics of the substrate/Ti-imido interaction, as the main factor in determining the selectivity of hydrocarbon (R) C [bond] H activation.     

Convenient synthesis of [3]catenane by olefin metathesis dimerizations

[3]Catenane 5a and 5b were synthesized conveniently by olefin metathesis dimerization of pseudorotaxanes 3a and 3b. The yields of 5a and 5b were influenced by concentrations of 3a and 3b, and a ring size of a center wheel of [3]catenane.     

Transition metal-catalyzed olefin arylation via C–H bond activation of arenes

In this article, two kinds of our transition metal-catalyzed olefin arylations are summarized and discussed. The first one is Ir-catalyzed novel anti-Markovnikov hydroarylation of olefins with benzene. Using this reaction catalyzed by [Ir(μ-acac-O,O′,C₃)(acac-O,O′)(acac-C₃)]₂ (acac = acetylacetonato), 1, straight-chain alkylarenes, which were not obtainable by the conventional Friedel-Crafts aromatic alkylation with olefins, were able to be successfully synthesized directly from arenes and olefins with the higher selectivity than that of branched alkylarenes. This is the first efficient catalyst which shows the desirable high regioselectivity. The reaction of benzene with propylene gave n-propylbenzene and cumene in 61% and 39% selectivities, respectively, and the reaction of benzene and styrene afforded 1,2-diphenylethane in 98% selectivity. The reaction of alkylarene and olefin showed meta and para orientations. A wide range of olefins and arenes can be employed for the synthesis of alkylarenes. The mechanism of the reaction involves C–H bond activation of benzene by Ir center to form Ir–phenyl species. The second reaction is Rh-catalyzed oxidative arylation of ethylene with benzene to directly produce styrene, namely one-step synthesis of styrene. The reaction of benzene with ethylene catalyzed by Rh(ppy)₂(OAc) (ppyH = 2-phenylpyridine, OAc = acetate), 3 with Cu oxidizing agent gave styrene and vinyl acetate in 77% and 23% selectivities, respectively, in contrast to those by Pd(OAc)₂, 47% of styrene and 53% of vinyl acetate. The mechanism of the reaction involves Rh-mediated C–H bond activation of benzene, which appears to be a rate-determining step. Furthermore, Rh complexes in a Rh(I) oxidation state at the beginning of the reaction work as catalysts for the reaction by addition of acacH and O₂ without any oxidizing agent, like Cu salt.     

Room temperature ring-opening metathesis of pyridines by a transient Ti[triple bond]C linkage

The transient titanium alkylidyne complex (PNP)TiCtBu (PNP = N[2-P(CHMe2)2-4-methylphenyl]2-), prepared from alpha-hydrogen abstraction of the corresponding alkylidene-alkyl species (PNP)Ti=CHtBu(CH2tBu), can readily cleave the C-N bond of N-heterocycles such as pyridine and 4-picoline at room temperature to afford azametallabicyclic systems. Experimental and theoretical studies strongly favor a ring-opening metathesis pathway where [2 + 2] cycloaddition of pyridine across the TiC linkage ultimately leads to C-N bond rupture.     

A double ring-closing olefin metathesis approach to [3]catenanes

A [3]catenane with peripheral olefinic macrocycles was conveniently synthesized via a double ring-closing olefin metathesis. Highlights of this work include the synthesis of a 65-membered macrocycle featuring two phenanthroline ligands, a Cu(I)-templated synthesis of a [3]pseudorotaxane, and the key double ring-closing olefin metathesis to afford the desired [3]catenane in 71% yield.     

Activation of arene C[bond]H bonds by a cationic hafnium silyl complex possessing an alpha-agostic Si[bond]H interaction

The reaction of Cp2Hf(SiMes2H)Me (1) with B(C6F5)3 produces zwitterionic Cp2Hf(eta2-SiHMes2)(mu-Me)B(C6F5)3 (2), which is stable for >8 h at -40 degrees C in toluene-d8. Spectroscopic data provide evidence for an unusual alpha-agostic Si-H interaction in 2. At room temperature, 2 reacts with the C-H bonds of aromatic hydrocarbons such as benzene and toluene to produce Cp2Hf(Ph)(mu-Me)B(C6F5)3 (3), isomers of Cp2Hf(C6H4Me)(mu-Me)B(C6F5)3 (4-6), and Cp2Hf(CH2Ph)(mu-Me)B(C6F5)3 (7), respectively. The reaction involving benzene is first-order in both 2 and benzene; rate = k[2][C6H6]. Mechanistic data including activation parameters (DeltaH = 19(1) kcal/mol; DeltaS = -17(3) eu), a large primary isotope effect of 6.9(7), and the experimentally determined rate law are consistent with a mechanism involving a concerted transition state for C-H bond activation.     

Protonolysis of a ruthenium-carbene bond and applications in olefin metathesis

The synthesis of a ruthenium complex containing an N-heterocylic carbene (NHC) and a mesoionic carbene (MIC) is described wherein addition of a Br?nsted acid results in protonolysis of the Ru-MIC bond to generate an extremely active metathesis catalyst. Mechanistic studies implicated a rate-determining protonation step in the generation of the metathesis-active species. The activity of the NHC/MIC catalyst was found to exceed those of current commercial ruthenium catalysts.     

Air stable,sterically hindered ferrocenyl dialkylphosphines for palladium-catalyzed C[bond]C,C[bond]N,and C[bond]O bond-forming cross-couplings

Pentaphenylferrocenyl di-tert-butylphosphine has been prepared in high yield from a two-step synthetic procedure, and the scope of various cross-coupling processes catalyzed by complexes bearing this ligand has been investigated. This ligand creates a remarkably general palladium catalyst for aryl halide amination and for Suzuki coupling. Turnovers of roughly 1000 were observed for aminations with unactivated aryl bromides or chlorides. In addition, complexes of this ligand catalyzed the formation of selected aryl ethers under mild conditions. The reactions encompassed electron-rich and electron-poor aryl bromides and chlorides. In the presence of catalysts containing this ligand, these aryl halides coupled with acyclic or cyclic secondary alkyl- and arylamines, with primary alkyl- and arylamines, and with aryl- and primary alkylboronic acids. These last couplings provide the first general procedure for reaction of terminal alkylboronic acids with aryl halides without toxic or expensive bases. The ligand not only generates highly active palladium catalysts, but it is air stable in solution and in the solid state. Palladium(0) complexes of this ligand are also air stable as a solid and react only slowly with oxygen in solution.     

Electronic and medium effects on the rate of arene C [bond] H activation by cationic Ir(III) complexes

A detailed mechanistic study of arene C [bond] H activation in CH(2)Cl(2) solution by Cp(L)IrMe(X) [L = PMe(3), P(OMe)(3); X = OTf, (CH(2)Cl(2))BAr(f); (BAr(f) = B[3,5-C(6)H(3)(CF(3))(2)](4))(-)] is presented. It was determined that triflate dissociation in Cp(L)IrMe(OTf), to generate tight and/or solvent-separated ion pairs containing a cationic iridium complex, precedes C [bond] H activation. Consistent with the ion-pair hypothesis, the rate of arene activation by Cp(L)IrMe(OTf) is unaffected by added external triflate salts, but the rate is strongly dependent upon the medium. Thus the reactivity of Cp(PMe(3))IrMe(OTf) can be increased by almost 3 orders of magnitude by addition of (n-Hex)(4)NBAr(f), presumably because the added BAr(f) anion exchanges with the OTf anion in the initially formed ion pair, transiently forming a cation/borate ion pair in solution (special salt effect). In contrast, addition of (n-Hex)(4)NBAr(f) to [CpPMe(3)Ir(Me)CH(2)Cl(2)][BAr(f)] does not affect the rate of benzene activation; here there is no initial covalent/ionic pre-equilibrium that can be perturbed with added (n-Hex)(4)NBAr(f). An analysis of the reaction between Cp(PMe(3))IrMe(OTf) and various substituted arenes demonstrated that electron-donating substituents on the arene increase the rate of the C [bond] H activation reaction. The rate of C(6)H(6) activation by [Cp(PMe(3))Ir(Me)CH(2)Cl(2)][BAr(f)] is substantially faster than [Cp(P(OMe)(3))Ir(Me)CH(2)Cl(2)][BAr(f)]. Density functional theory computations suggest that this is due to a less favorable pre-equilibrium for dissociation of the dichloromethane ligand in the trimethyl phosphite complex, rather than to a large electronic effect on the C [bond] H oxidative addition transition state. Because of these combined effects, the overall rate of arene activation is increased by electron-donating substituents on both the substrate and the iridium complex.     

Intramolecular metathesis of a vinyl group with vinylidene C=C double bond in Ru complexes

The cationic complex {[Ru]=C=CHCPh2CH2CH=CH2}BF4 (3a, [Ru] = (eta5-C5H5)(PPh3)2Ru) in solution transforms to {[Ru]=C=CHCH2CPh2CH=CH2}BF4 (4a) via a new metathesis process of the terminal vinyl group with the C=C of the vinylidene group which is confirmed by 13C labeling studies. This transformation is irreversible as revealed by deuteration and decomplexation studies. The cationic complex {[Ru]=C=CHCPh2CH2CMe=CH2}BF4 (3b) undergoes a cyclization process yielding 6b containing a eta2-cyclic allene ligand which is fully characterized by single-crystal X-ray diffraction analysis. Analogous complexes 4a' and 6b' ([Ru] = (eta5-C5H5)(dppe)Ru) containing dppe ligands were similarly obtained from protonation of the corresponding acetylide complexes via formation of vinylidene intermediate. Protonation of the acetylide complex containing a terminal alkynyl group [Ru]-CCCPh2CH2CCH (2c) generates the vinylidene complex {[Ru]=C=CHCPh2CH2CCH}BF4 (3c) which again undergoes an irreversible transformation to give {[Ru]=C=CHCH2CPh2CCH}BF4 (4c) possibly via a pi-coordinated alkynyl complex followed by hydrogen and metal migration. No similar transformation is observed for the analogous dppe complex 3c'. With an extra methylene group, complex {[Ru]=C=CHCPh2CH2CH2CH=CH2}BF4 (3d) and complex {[Ru]=C=CHCPh2CH2Ph}BF4 (3e) are stable. The presence of a gem-diphenylmethylene moiety at the vinylidene ligand with the appropriate terminal vinyl or alkynyl group along with the correct steric environment implements such a novel reactivity in the ruthenium vinylidene complexes.     

Synthesis of the EF-ring of ciguatoxin 3C based on the [2,3]-Wittig rearrangement and ring-closing olefin metathesis

The EF-ring segment of ciguatoxin 3C, a causative toxin of ciguatera fish poisoning, was synthesized in three major steps: 1,4-addition for the C20O-C27 bond connection, chirality transferring anti selective [2,3]-Wittig rearrangement for the construction of the anti-2-hydroxyalkyl ether part, and ring-closing olefin metathesis for the F-ring formation.     

Enantioselective synthesis of [7]helicene: dramatic effects of olefin additives and aromatic solvents in asymmetric olefin metathesis

The asymmetric synthesis of [7]helicene was accomplished in good ee (80%) by kinetic resolution by means of asymmetric olefin metathesis. Three key factors contributed to the success of the kinetic resolution: the use of new Ru-based olefin metathesis catalysts bearing C1-symmetric N-heterocyclic carbene ligands, simple olefins as additives to control the nature of the propagating alkylidene and hexafluorobenzene as a solvent.     

Total synthesis of (-)-rhazinilam: asymmetric C[bond]H bond activation via the use of a chiral auxiliary

The antitumor agent (-)-rhazinilam was synthesized in three major steps, namely the pyrrole synthesis, selective C[bond]H bond activation, and direct macrolactam formation. The key step involved asymmetric C[bond]H bond functionalization (dehydrogenation) of the diethyl group segment in intermediate 6. This was achieved by the attachment of chiral platinum complexes to the proximal nitrogen atom. A high degree of selectivity (60-75% ee) was achieved via the use of oxazolinyl ketone chiral auxiliaries.     

Equatorial preference in the C[bond]H activation of cycloalkanes: GaCl3-catalyzed aromatic alkylation reaction

GaCl(3) catalyzes the aromatic alkylation of naphthalene or phenanthrene using cycloalkanes. The C[bond]C formation predominantly takes place at the least hindered positions of the substrates, and equatorial isomers regarding the cycloalkane moiety are generally obtained. The reaction of bicyclo[4.4.0]decane and naphthalene occurs at the 2-position of naphthalene and at the 2- or 3-carbons of the cycloalkane, and the products possess a trans configuration at the junctures and an equatorial configuration at the naphthyl groups. Notably, cis-bicyclo[4.4.0]decane turns out to be much more reactive than the trans isomer, and a turnover number "TON" up to 20 based on GaCl(3) is attained. 1,2-Dimethylcyclohexane reacts similarly, and the cis isomer is more reactive than the trans isomer. Monoalkylcycloalkanes react at the secondary carbons provided that the alkyl group is smaller than tert-butyl. Adamantanes react at the tertiary 1-position. The alkylation reaction is considered to involve the C[bond]H activation of cycloalkanes with GaCl(3) at the tertiary center followed by the migration of carbocations and electrophilic aromatic substitution yielding thermodynamically stable products. The stereochemistry of the reaction reveals that GaCl(3) activates the equatorial tertiary C[bond]H rather than the axial tertiary C[bond]H.