C-C and C-H bond activation reactions in N-heterocyclic carbene complexes of ruthenium

Thermolysis of Ru(PPh3)3(CO)H2 with the N-heterocyclic carbene bis(1,3-(2,4,6-trimethylphenyl)imidazol-2-ylidene) (IMes) results in C-C activation of an Ar-CH3 bond in one of the mesityl rings of the carbene ligand. Upon addition of IMes to Ru(PPh3)3(CO)H2 at room temperature in the presence of an alkene, C-H bond activation is observed instead. The thermodynamics of these C-C and C-H cleavage reactions have been probed using density functional theory.     

C-C, C-O and C-N bond formation via rhodium(III)-catalyzed oxidative C-H activation

Rhodium(III)-catalyzed direct functionalization of C-H bonds under oxidative conditions leading to C-C, C-N, and C-O bond formation is reviewed. Various arene substrates bearing nitrogen and oxygen directing groups are covered in their coupling with unsaturated partners such as alkenes and alkynes. The facile construction of C-E (E = C, N, S, or O) bonds makes Rh(III) catalysis an attractive step-economic approach to value-added molecules from readily available starting materials. Comparisons and contrasts between rhodium(III) and palladium(II)-catalyzed oxidative coupling are made. The remarkable diversity of structures accessible is demonstrated with various recent examples, with a proposed mechanism for each transformation being briefly summarized (critical review, 138 references).     

Palladium-catalyzed intramolecular C-H activation/C-C bond formation: a straightforward synthesis of phenanthridines

The palladium-catalyzed intramolecular C-H activation/C-C cross-coupling has been developed for a straightforward and efficient synthesis of phenanthridines. With Pd(OAc)(2) (4 mol %) as the catalyst, PCy(3) (8 mol %) as the ligand, and Cs(2)CO(3) as the base, this protocol was applied to synthesize a small library of phenanthridine derivatives in good yields in THF.     

Oxidative C-H activation/C-C bond forming reactions: synthetic scope and mechanistic insights

This paper describes a new palladium-catalyzed method for C-H activation/carbon-carbon bond formation with hypervalent iodine arylating agents. This transformation has been applied to a variety of arene and benzylic substrates containing different directing groups (pyridines, quinolines, oxazolidinones, and amides) and proceeds with high levels of regiocontrol. Mechanistic experiments provide preliminary evidence in support of an unusual mechanism for this transformation involving a Pd(II)/Pd(IV) catalytic cycle.     

Branch-selective reductive coupling of 2-vinyl pyridines and imines via rhodium catalyzed C-C bond forming hydrogenation

Hydrogenation of 2-vinyl azines 1a-1e in the presence of N-arylsulfonyl imines 2a-2l at ambient temperature and pressure employing cationic rhodium catalysts ligated by tri-2-furylphosphine results in regioselective reductive coupling to furnish branched products of imine addition 3a-3v, which embody modest to high levels of syn-diastereoselectivity. Catalytic coupling of 6-bromo-2-vinylpyridine 1a to imine 2l under an atmosphere of elemental deuterium provides deuterio-3l, with deuterium exclusively at the former beta-position of the vinyl moiety. These data are consistent with a catalytic mechanism involving oxidative coupling of the vinyl azine and imine partners to furnish a cationic aza-rhodacyclopentane, which upon deuteriolytic cleavage releases the adduct and regenerates cationic rhodium(I) to close the catalytic cycle. These studies represent the first metal catalyzed reductive C-C couplings of vinyl azines.     

C-C bond formation via C-H bond activation: synthesis of the core of teleocidin B4

The core of teleocidin B4, a complex fragment of a natural product containing two quaternary stereocenters and a penta-substituted benzene ring, was synthesized in four C-C bond-forming steps starting from tert-butyl derivative 1. The first step involved alkenylation of the tert-butyl group with a vinyl boronic acid, followed by the successful annulation of the cyclohexane ring to the benzene nucleus via an intramolecular Friedel-Crafts reaction. The third step required a diastereoselective oxidative carbonylation of the geminal dimethyl group, followed at last by indole assembly via the alkenylation of the phenol nucleus, to afford the teleocidin B4 core. Noteworthy is the fact that steps 1 and 3 critically depended on the directing role of the aniline nitrogen (directed C-H bond functionalization).     

C-H activation reactions of ruthenium N-heterocyclic carbene complexes: application in a catalytic tandem reaction involving C-C bond formation from alcohols

A series of ruthenium hydride N-alkyl heterocyclic carbene complexes has been investigated as catalysts for a tandem oxidation/Wittig/reduction reaction to give C-C bonds from alcohols. The C-H-activated carbene complex Ru(IiPr(2)Me(2))'(PPh(3))(2)(CO)H (9) proves to be the most active precursor catalyzing the reaction of PhCH(2)OH and Ph(3)P=CHCN in 3 h at 70 degrees C. These results provide (a) a rare case in which N-alkyl carbenes afford higher catalytic activity than their N-aryl counterparts and (b) a novel example of the importance of NHC C-H activation in a catalytic cycle.     

Ligand properties of aromatic azines: C-H activation, metal induced disproportionation and catalytic C-C coupling reactions

The reaction of aromatic azines with Fe₂(CO)₉ yields dinuclear iron carbonyl cluster compounds as the main products. The formation of these compounds may be rationalized by a C-H activation reaction at the aromatic substituent in ortho position with respect to the exocyclic C-N double bond followed by an intramolecular shift of the corresponding hydrogen atom toward the former imine carbon atom. The second imine function of the ligand does not react. Additional products arise from the metal induced disproportionation of the azine into a primary imine and a nitrile. So also one of the imine C-H bonds may be activated during the reaction. Depending on the aromatic substituent of the azine ligands iron carbonyl complexes of the disproportionation products are isolated and characterized by X-ray crystallography. C-C coupling reactions catalyzed by Ru₃(CO)₁₂ result in the formation of ortho-substituted azines. In addition, ortho-substituted nitriles are identified as side-products showing that the metal induced disproportionation reaction also takes place under catalytic conditions.     

Methylene transfer from SnMe groups mediated by a rhodium(I) pincer complex: Sn-C, C-C, and C-H bond activation

The PCP-Rh(I) complex 1a based on the [1,3-phenylenebis(methylene)]bis(diisopropylphosphine) ligand reacts with [diazo(phenyl)methyl]trimethylstannane (2) at room temperature to give novel pincer-type phenyl(dimethylstannyl)methylene]hydrazinato complex 3a. The reaction sequence involves a unique combination of Sn-C bond cleavage, C-C bond formation, C-H activation and intramolecular deprotonation of a rhodium hydride intermediate, which results in methylene transfer from an SnMe group to the pincer system and PCP-chelate expansion. A methylene-transfer reaction was also demonstrated with tetramethyltin as the methylene source in the presence of KOC(CH(3))(3) at room temperature. The resulting unstable "chelate-expanded" Rh(I) complex [(C(10)H(5)(CH(2)PiPr(2))(2))(CH(2))Rh(L)] (L=N(2), THF; 4a) was isolated as its carbonyl derivative 5a. Heating 4a in benzene yielded an equimolar amount of toluene and 1a, which demonstrates the ability of the Rh(I) pincer complex to extract a methylene group from an unactivated alkyl tin substrate and transfer it, via C-C followed by C-H activation, to an arene. Use of fluorobenzene resulted in formation of fluorotoluene. Catalytic methylene-group transfer mediated by 1a was not possible, because of formation of o-xylylene complex 8 under the reaction conditions. Steric parameters play a decisive role in the reactivity with tin compounds; while iPrP derivative 1 a underwent facile reactions, tBuP complex 1b was inert.     

Nickel-catalyzed alkenylation and alkylation of fluoroarenes via activation of C-H bond over C-F bond

Nickel/P(c-C(5)H(9))(3) (PCyp(3)) catalyst effects the addition reactions of fluoroarenes across alkynes, 1,3-dienes, and vinylarenes via the activation of C-H bonds over C-F bonds. The acidic C-H bonds located ortho to fluorine are exclusively activated to afford a range of alkenylated and alkylated fluoroarenes.     

C-C bond formation via C-H bond activation: catalytic arylation and alkenylation of alkane segments

A new system for catalytic arylation and alkenylation of alkane segments has been developed. The ortho-tert-butylaniline substrates and 2-pivaloylpyridine may be arylated and alkenylated at the tert-butyl group, while no functionalization occurred at more reactive C-H and other bonds. Arylation and alkenylation of these substrates are achieved in the presence of Ph2Si(OH)Me and Ph-CH=CH-Si(OH)Me2, respectively, and the catalytic amount of Pd(OAc)2 and stoichiometric oxidant (Cu(OAc)2, 2 equiv) in DMF. In contrast, the ortho-i-propylaniline substrate underwent cyclopalladation, but no arylation product was obtained. Complex compound 14 was synthesized via tandem arylation-alkenylation of tert-butylaniline 11. We hypothesize that the high selectivity of this system stems from the confluence of directing effect of the Schiff base or pyridine moiety and unique reactivity properties of a phenyl-palladium acetate species (Ph-Pd-OAc.Ln).     

A convergent and enantioselective synthesis of (+)-amurensinine via selective C-H and C-C bond insertion reactions

A convergent and enantioselective synthesis of the natural product amurensinine is described. The synthetic strategy takes advantage of mild and selective C-H and C-C bond insertion reactions, in addition to the palladium-catalyzed aerobic oxidative kinetic resolution recently developed in these laboratories.     

Oxidative coupling of platinum arylamides: temperature dependent C-H or C-F cleavage

The oxidation of an arylamido platinum complex leads to C-C coupling with selective C-H versus C-F bond cleavage depending on the reaction temperature.     

Regioselective functionalization of iminophosphoranes through Pd-mediated C-H bond activation: C-C and C-X bond formation

The orthopalladation of iminophosphoranes [R(3)P=N-C(10)H(7)-1] (R(3) = Ph(3) 1, p-Tol(3) 2, PhMe(2) 3, Ph(2)Me 4, N-C(10)H(7)-1 = 1-naphthyl) has been studied. It occurs regioselectively at the aryl ring bonded to the P atom in 1 and 2, giving endo-[Pd(μ-Cl)(C(6)H(4)-(PPh(2=N-1-C(10)H(7))-2)-κ-C,N](2) (5) or endo-[Pd(μ-Cl)(C(6)H(3)-(P(p-Tol)(2)=N-C(10)H(7)-1)-2-Me-5)-κ-C,N](2) (6), while in 3 the 1-naphthyl group is metallated instead, giving exo-[Pd(μ-Cl)(C(10)H(6)-(N=PPhMe(2))-8)-κ-C,N](2) (7). In the case of 4, orthopalladation at room temperature affords the kinetic exo isomer [Pd(μ-Cl)(C(10)H(6)-(N=PPh(2)Me)-8)-κ-C,N](2) (11exo), while a mixture of 11exo and the thermodynamic endo isomer [Pd(μ-Cl)(C(6)H(4)-(PPhMe=N-C(10)H(7)-1)-2)-κ-C,N](2) (11endo) is obtained in refluxing toluene. The heating in toluene of the acetate bridge dimer [Pd(μ-OAc)(C(10)H(6)-(N=PPh(2)Me)-8)-κ-C,N](2) (13exo) promotes the facile transformation of the exo isomer into the endo isomer [Pd(μ-OAc)(C(6)H(4)-(PPhMe=N-C(10)H(7)-1)-2)-κ-C,N](2) (13endo), confirming that the exo isomers are formed under kinetic control. Reactions of the orthometallated complexes have led to functionalized molecules. The stoichiometric reactions of the orthometallated complexes [Pd(μ-Cl)(C(10)H(6)-(N=PPhMe(2))-8)-κ-C,N](2) (7), [Pd(μ-Cl)(C(6)H(4)-(PPh(2)[=NPh)-2)](2) (17) and [Pd(μ-Cl)(C(6)H(3)-(C(O)N=PPh(3))-2-OMe-4)](2) (18) with I(2) or with CO results in the synthesis of the ortho-halogenated compounds [PhMe(2)P=N-C(10)H(6)-I-8] (19), [I-C(6)H(4)-(PPh(2)=NPh)-2] (21) and [Ph(3)P=NC(O)C(6)H(3)-I-2-OMe-5] (23) or the heterocycles [C(10)H(6)-(N=PPhMe(2))-1-(C(O))-8]Cl (20), [C(6)H(5)-(N=PPh(2)-C(6)H(4)-C(O)-2]ClO(4) (22) and [C(6)H(3)-(C(O)-1,2-N-PPh(3))-OMe-4]Cl (24).     

C-H bond activation and subsequent C-C bond formation promoted by osmium: 2-vinylpyridine-acetylene couplings

Complex OsH2Cl2(PiPr3)2 promotes the C-H activation of 2-vinylpyridine and subsequently couples the activated substrate with a second 2-vinylpyridine and two acetylene molecules. In the absence of 2-vinylpyridine, the activated substrate is coupled with an acetylene unit to afford a 2-butadienylpyridine derivative.     

Heterogenised N-heterocyclic carbene complexes: synthesis, characterisation and application for hydroformylation and C-C bond formation reactions

The imidazolium salts: 1-mesityl-3-(3-trimethoxysilylpropyl)imidazolium iodide and 1-tert-butyl-3-(3-trimethoxysilylpropyl)imidazolium iodide, abbreviated as (tmpMes)HI (3a) and (tmp(t)Bu)HI (3b), respectively, have been synthesised. The palladium(ii) complexes (η(3)-C(3)H(5)) (tmpMes)PdCl (5a) and (η(3)-C(3)H(5))(tmp(t)Bu)PdCl (5b), rhodium(i) and iridium(i) complexes (η(4)-1,5-COD) (tmpMes)MCl, M = Rh (6a), Ir (7a) and (η(4)-1,5-COD)(tmp(t)Bu)MCl, where M = Rh (6b), Ir (7b), were synthesised by silver transmetallation reactions using the silver(i) complexes (tmpMes)AgI (4a) and (tmp(t)Bu)AgI (4b). The iridium complex 7b has been structurally characterised. The Pd(ii) and Rh(i) complexes have been immobilised by attachment to chemically modified MCM-41. The immobilised palladium(ii) materials have been tested as recyclable catalysts for Suzuki type C-C bond formation reactions in water and the immobilised rhodium(i) materials have been examined for their catalytic ability for the hydroformylation of 1-octene.     

Synthesis and reactivity of silyl ruthenium complexes: the importance of trans effects in C-H activation,Si-C bond formation,and dehydrogenative coupling of silanes

A series of octahedral ruthenium silyl hydride complexes, cis-(PMe(3))(4)Ru(SiR(3))H (SiR(3) = SiMe(3), 1a; SiMe(2)CH(2)SiMe(3), 1b; SiEt(3), 1c; SiMe(2)H, 1d), has been synthesized by the reaction of hydrosilanes with (PMe(3))(3)Ru(eta(2)-CH(2)PMe(2))H (5), cis-(PMe(3))(4)RuMe(2) (6), or (PMe(3))(4)RuH(2) (9). Reaction with 6 proceeds via an intermediate product, cis-(PMe(3))(4)Ru(SiR(3))Me (SiR(3) = SiMe(3), 7a; SiMe(2)CH(2)SiMe(3), 7b). Alternatively, 1 and 7 have been synthesized via a fast hydrosilane exchange with another cis-(PMe(3))(4)Ru(SiR(3))H or cis-(PMe(3))(4)Ru(SiR(3))Me, which occurs at a rate approaching the NMR time scale. Compounds 1a, 1b, 1d, and 7a adopt octahedral geometries in solution and the solid state with mutually cis silyl and hydride (or silyl and methyl) ligands. The longest Ru-P distance within a complex is always trans to Si, reflecting the strong trans influence of silicon. The aptitude of phosphine dissociation in these complexes has been probed in reactions of 1a, 1c, and 7a with PMe(3)-d(9) and CO. The dissociation is regioselective in the position trans to a silyl ligand (trans effect of Si), and the rate approaches the NMR time scale. A slower secondary process introduces PMe(3)-d(9) and CO in the other octahedral positions, most likely via nondissociative isomerization. The trans effect and trans influence in 7a are so strong that an equilibrium concentration of dissociated phosphine is detectable (approximately 5%) in solution of pure 7a. Compounds 1a-c also react with dihydrogen via regioselective dissociation of phosphine from the site trans to Si, but the final product, fac-(PMe(3))(3)Ru(SiR(3))H(3) (SiR(3) = SiMe(3), 4a; SiMe(2)CH(2)SiMe(3), 4b; SiEt(3), 4c), features hydrides cis to Si. Alternatively, 4a-c have been synthesized by photolysis of (PMe(3))(4)RuH(2) in the presence of a hydrosilane or by exchange of fac-(PMe(3))(3)Ru(SiR(3))H(3) with another HSiR(3). The reverse manifold - HH elimination from 4a and trapping with PMe(3) or PMe(3)-d(9) - is also regioselective (1a-d(9)() is predominantly produced with PMe(3)-d(9) trans to Si), but is very unfavorable. At 70 degrees C, a slower but irreversible SiH elimination also occurs and furnishes (PMe(3))(4)RuH(2). The structure of 4a exhibits a tetrahedral P(3)Si environment around the metal with the three hydrides adjacent to silicon and capping the P(2)Si faces. Although strong Si...HRu interactions are not indicated in the structure or by IR, the HSi distances (2.13-2.23(5) A) suggest some degree of nonclassical SiH bonding in the H(3)SiR(3) fragment. Thermolysis of 1a in C(6)D(6) at 45-55 degrees C leads to an intermolecular CD activation of C(6)D(6). Extensive H/D exchange into the hydride, SiMe(3), and PMe(3) ligands is observed, followed by much slower formation of cis-(PMe(3))(4)Ru(D)(Ph-d(5)). In an even slower intramolecular CH activation process, (PMe(3))(3)Ru(eta(2)-CH(2)PMe(2))H (5) is also produced. The structure of intermediates, mechanisms, and aptitudes for PMe(3) dissociation and addition/elimination of H-H, Si-H, C-Si, and C-H bonds in these systems are discussed with a special emphasis on the trans effect and trans influence of silicon and ramifications for SiC coupling catalysis.     

First regioselective cyclometalation reactions of cobalt in arylketones: C-H versus C-F activation

Phenyl ketones react smoothly under mild conditions with low valent cobalt(i) adducts to form new and stable five-membered cobaltacycles via C-H and C-F activation.