Chelation-assisted carbon-hydrogen and carbon-carbon bond activation by transition metal catalysts

Herein we describe the chelation-assisted C-H and C-C bond activation of carbonyl compounds by Rh1 catalysts. Hydroacylation of olefins was accomplished by utilizing 2-amino-3-picoline as a chelation auxiliary. The same strategy was employed for the C-C bond activation of unstrained ketones. Allylamine 24 was devised as a synthon of formaldehyde. Hydroiminoacylation of alkynes with allylamine 24 was applied to the alkyne cleavage by the aid of cyclohexylamine.     

β-Carbonyl radicals as three-carbon building blocks for carbon-carbon bond forming reactions

From aldehydes, ketones and esters β-carbonyl radicals $\text{47}$ can be generated via enolization, cyclopropanation, solvomercuration and reduction with NaBH₄. Radicals $\text{47}$ react with electron-poor alkenes $\text{27}$ to give products of CC-bond forming reactions (Tables 1–3). Carbonyl compounds are therefore precursors of three-carbon building blocks. The products result from reactions with “Umpolung”.     

Powerful carbon-carbon bond forming reactions based on a novel radical exchange process

Xanthates and related derivatives have proved to be extremely useful for both inter- and intramolecular radical additions. The broad applicability of the intermolecular addition to un-activated olefins opens tremendous opportunities for synthesis, since various functional groups can be brought together under mild conditions and complex structures can be rapidly assembled. The presence of the xanthate in the product is also a powerful asset for further modifications, by both radical and non-radical pathways. Of special importance is the access to highly substituted aromatic and heteroaromatic derivatives and the synthesis of block polymers through a controlled radical polymerisation mediated by various thiocarbonylthio group containing agents (RAFT and MADIX processes).     

Copper-catalyzed oxidative cleavage of carbon-carbon double bond of enol ethers with molecular oxygen

A novel CC bond cleavage reaction of aromatic enol ethers (1) to give ketones (2) using molecular oxygen as oxidant is described. Among the examined catalysts (Cu(II), Pd(II), Ru(II), and H⁺), CuCl₂ exhibited the highest activity. The reaction proceeded smoothly with several kinds of substrates.     

Photosensitized (electron transfer) carbon-carbon bond cleavage of radical cations : The diphenylmethyl system

The photosensitized (electron transfer) reaction of methyl 2,2-diphenylethyl ether (1), 1,1,2,2-tetraphenylethane (5), 2-methyl-1,1,2-triphenylpropane (6), and 2-methoxy-2-diphenylmethylnorbornane (11 endo and exo) with 1,4-dicyanobenzene (4) in acetonitrile-methanol leads to products indicating cleavage of an intermediate radical cation to give the diphenylmethyl radical and a carbocation. The diphenylmethyl radical is then reduced by the radical anion of the photosensitizer and protonated to yield diphenylmethane. The carbocation fragment reacts with methanol to yield ether and/or acetals. The effect of temperature on the efficiency of cleavage of 5 and 6 has been analyzed. The increase in efficiency observed at higher temperatures reflects an activation energy for the cleavage of the radical cations. In cases where no cleavage is observed, the activation energy for cleavage may be so high that back electron transfer from the radical anion of the pbotosensitizer is the dominant reaction. The C—C bond dissociation energies of the radical cations of 5 and 6 were estimated by analysis of the thermochemical cycle using the bond dissociation energies and the oxidation potentials of the neutral molecules and the oxidation potential of the diphenylmethyl and cumyl radicals. The direction of cleavage of the radical cation is explained in terms of the relative oxidation potentials of the two possible radicals.     

Binaphthol-derived phosphoric acid as a versatile catalyst for enantioselective carbon-carbon bond forming reactions

Binaphthol-derived monophosphoric acids have been designed as novel chiral Br?nsted-acid catalysts. The chiral phosphoric acids thus developed function as efficient enantioselective catalysts for a variety of organic transformations, especially for carbon-carbon bond forming reactions.     

Structure-reactivity relationships in oxidative carbon-carbon bond forming reactions: a mild and efficient approach to stereoselective syntheses of 2,6-disubstituted tetrahydropyrones

Homobenzylic ethers with pendent enol acetate nucleophiles undergo highly efficient cleavage reactions followed by 6-endo cyclizations to form 2,6-disubstituted tetrahydropyrones with excellent stereocontrol at room temperature in the presence of the mild oxidant ceric ammonium nitrate. Cyclizations proceed through either stabilized or nonstabilized oxocarbenium ions. Structure-reactivity relationships are presented to provide a predictive guide for the design of radical cation cleavage processes. Unique sequences for preparing cyclization substrates based on stereoselective Lewis acid mediated acetal openings have been developed for the synthesis of complex substrates that are suitable for applications to the synthesis of biologically active natural products.     

Efficient nickel mediated carbon-carbon bond cleavage of organonitriles

The reactions of the nickel complex [Ni(2)(iPr(2)Im)4(COD)] 1 with organonitriles smoothly and irreversibly proceed via intermediates with eta(2)-coordinated organonitrile ligands such as [Ni(iPr(2)Im)2(eta(2)-(CN)-PhCN)] 2 and [Ni(iPr(2)Im)2(eta(2)-(CN)-pTolCN)] 4 to yield aryl cyanide complexes of the type trans-[Ni(iPr(2)Im)2(CN)(Ar)] (Ar = Ph 3, pTol 5, 4-CF(3)C(6)H(4) 6, 2,4-(OMe)2C(6)H(3) 7, 2-C(4)H(3)O 8, 2-C(5)H(4)N 9). The compounds 3, 7, 9 and have been structurally characterized. For the conversion of 2 to 3 a free activation enthalpy DeltaG++(328 K) of 103.47 +/- 0.79 kJ mol(-1) was calculated from time dependent NMR spectroscopy. The analogous reaction of arylnitriles with electron releasing substituents or heteroaromatic organonitriles is significantly faster compared to the reaction with benzonitrile or toluonitrile. The reactions of 1 with acetonitrile or trimethylsilyl cyanide afforded [Ni(iPr(2)Im)2(CN)(Me)] 10 and structurally characterized [Ni(iPr(2)Im)2(CN)(SiMe(3))] 11. The usage of an organonitrile with a longer alkyl chain, adiponitrile, yielded [Ni(iPr(2)Im)2(eta(2)-(CN)-NCC(4)H(8)CN)] 12 as well as the C-CN activation product [Ni(iPr(2)Im)2(CN)(C(4)H(8)CN)]13 in thermal and photochemical reactions, although this pathway seems to be significantly interfered with by decomposition pathways under the formation of the dicyanide complex [Ni(iPr(2)Im)(2)(CN)(2)] 14.     

Regioselective carbon-carbon bond cleavage in the oxidation of cyclopropenylcarbinols

The strained double bond of cyclopropenylcarbinols undergoes a facile oxidation reaction to lead to unsaturated carbonyl derivatives. The distribution of the formed products depends on the relative stability of carbon-centered radical species, and the Sharpless kinetic resolution leads to enantiomerically pure Baylis-Hillman enal adducts.     

Lewis acid promoted carbon-carbon bond cleavage of gamma-silyloxy-beta-hydroxy-alpha-diazoesters

Cyclic gamma-silyloxy-beta-hydroxy-alpha-diazoesters undergo efficient rupture of the Cbeta-Cgamma bond when treated with tin tetrachloride to provide tethered aldehyde ynoate products in high yield.     

Synthesis of sulfur-containing heterocycles through oxidative carbon-hydrogen bond functionalization

Vinyl sulfides react rapidly and efficiently with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) to form α,β-unsaturated thiocarbenium ions through oxidative carbon-hydrogen bond cleavage. These electrophiles couple with appended π-nucleophiles to yield sulfur-containing heterocycles through carbon-carbon bond formation. Several nucleophiles are compatible with the procedure, and the reactions generally proceed through readily predictable transition states.     

Cleavage of a carbon-carbon triple bond via gold-catalyzed cascade cyclization/oxidative cleavage reactions of (Z)-enynols with molecular oxygen

A highly efficient carbon-carbon triple bond cleavage reaction of (Z)-enynols was developed, which offered a new route to highly substituted butenolides. The methodology is realized by a tandem reaction using a single gold(I) catalyst, which could catalyze different reactions of cyclization/oxidative cleavage in the same vessel.     

Carbon dioxide as a carbon source in organic transformation: carbon-carbon bond forming reactions by transition-metal catalysts

Recent carbon-carbon bond forming reactions of carbon dioxide with alkenes, alkynes, dienes, aryl zinc compounds, aryl boronic esters, aryl halides, and arenes having acidic C-H bonds are reviewed in which transition-metal catalysts play an important role.     

Consecutive carbon-carbon bond formation approach in tandem cyclization reactions

The conventional tandem cyclization reactions involve the formation of alternating carbon-carbon bonds, whereas the newly developed cyclization reactions involve the formation of consecutive carbon-carbon bonds, in which N-aziridinylimines have been utilized as geminal radical acceptor and donor equivalents in a single operation. This unprecedented tandem cyclization approach becomes feasible by the successful generation of 5- and 6-membered ring radicals by radical cyclizations of N-aziridinylimines. The same notion can be applied to the anionic cyclizations of N-aziridinylimines, thereby allowing anionic consecutive carbon-carbon bond formation. This approach has great synthetic potential, particularly for the construction of quaternary carbon centers, and it provides highly efficient routes for the synthesis of natural products.     

Palladium-catalyzed sequential carbon-carbon bond cleavage/formation producing arylated benzolactones

3-(2-Hydroxyphenyl)cyclobutanones react with aryl bromides in the presence of palladium catalysts to afford 4-arylmethyl-3,4-dihydrocoumarins in high yields through a sequence involving carbon-carbon bond cleavage and formation. In the case of the reaction with 2-(2-hydroxyphenyl)cyclobutanones, five- or seven-membered lactones were produced depending on the presence of an additional substituent at the 2-position.     

Steady-state and laser flash photolysis study of the carbon-carbon bond fragmentation reactions of 2-arylsulfanyl alcohol radical cations

The N-methylquinolinium tetrafluoroborate (NMQ(+))-sensitized photolysis of the erythro-1,2-diphenyl-2-arylsulfanylethanols 1-3 (1, aryl = phenyl; 2, aryl = 4-methylphenyl; 3, aryl = 3-chlorophenyl) has been investigated in MeCN, under laser flash and steady-state photolysis. Under laser irradiation, the formation of sulfide radical cations of 1-3, in the monomeric (lambda(max) = 520-540 nm) and dimeric form (lambda(max) = 720-->800 nm), was observed within the laser pulse. The radical cations decayed by first-order kinetics, and under nitrogen, the formation of ArSCH(*)Ph (lambda(max) = 350-360 nm) was clearly observed. This indicates that the decay of the radical cation is due to a fragmentation process involving the heterolytic C-C bond cleavage, a conclusion fully confirmed by steady-state photolysis experiments (formation of benzaldehyde and the dimer of the alpha-arylsulfanyl carbon radical). Whereas the fragmentation rate decreases as the C-C bond dissociation energy (BDE) increases, no rate change was observed by the replacement of OH by OD in the sulfide radical cation (k(OH)/k(OD) = 1). This suggests a transition state structure with partial C-C bond cleavage where the main effect of the OH group is the stabilization of the transition state by hydrogen bonding with the solvent. The fragmentation rate of 2-hydroxy sulfanyl radical cations turned out to be significantly slower than that of nitrogen analogues of comparable reduction potential, probably due to a more efficient overlap between the SOMO in the heteroatom and the C-C bond sigma-orbital in the second case. The fragmentation rates of 1(+*)-3(+*) were found to increase by addition of a pyridine, and plots of k(base) against base strength were linear, allowing calculation of the beta Bronsted values, which were found to increase as the reduction potential of the radical cation decreases, beta = 0.21 (3(+*)), 0.34 (1(+*)), and 0.48 (2(+*)). The reactions of 1(+*) exhibit a deuterium kinetic isotope effect with values that increase as the base strength increases: k(OH)/k(OD) = 1.3 (pyridine), 1.9 (4-ethylpyridine), and 2.3 (4-methoxypyridine). This finding and the observation that with the above three bases the rate decreases in the order 3(+*) > 1(+*) > 2(+*), i.e., as the C-C BDE increases, suggest that C-C and O-H bond cleavages are concerted but not synchronous, with the role of OH bond breaking increasing as the base becomes stronger (variable transition state). It is probable that, with the much stronger base, 4-(dimethylamino)pyridine, a change to a stepwise mechanism may occur where the slow step is the formation of a radical zwitterion that then rapidly fragmentates to products.