Carbonyl Insertion Research Articles

Cobalt-Catalyzed Reductive C-O Bond Cleavage of Lignin β-O-4 Ketone Models via In Situ Generation of the Cobalt-Boryl Species.

An efficient and mild method for reductive C-O bond cleavage of lignin β-O-4 ketone models was developed to afford the corresponding ketones and phenols with PDI-CoCl2 as the precatalyst and diboron reagent as the reductant. The synthetic utility of the methodology was demonstrated by depolymerization of a polymeric model and gram-scale transformation. Mechanistic studies suggested that this transformation involves steps of carbonyl insertion, 1,2-Brook type rearrangement, β-oxygen elimination, and rate-limiting regeneration of the catalytic active Co-B species.

Recent Advances in Synthesis of 3,4‐Dihydroisoquinolin‐1(2H)‐one

AbstractThe 3,4‐dihydroisoquinolin‐1(2H)‐one motifs found in many natural products, synthetic molecules with a diverse range of the biological activities and represent a privilege scaffold. Thereby the number of the innovative synthetic methodologies has been reported for constructions of this scaffold, which includes metal catalyzed and metal free method, multicomponent, domino one pot protocol, oxidation, Friedel‐Crafts type of cyclization. In the recent years many general protocols for the construction of this scaffold were reported in the literature and there is no focussed individual review for the 3,4‐dihydroisoquinolin‐1(2H)‐one since 2001. This review focuses on the reports describing the new method for the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐one, published since 2001 to till date. In this review, we approach method of the synthesis of 3,4‐dihydroisoquinolin‐1(2H)‐one according to the strategy used for its synthesis, which includes, the intramolecular cyclization of carbamate/ urea/ thiourea/ isocyanate/ azidoamide, carbonylation/ carbomylation/ carbonyl insertion, metal catalyzed protocols by C−H activation by directing group, metal free domino procedures and oxidations of isoquinoline derivatives that were included in recent publications. Moreover, the reports published since 2001 for the synthesis of the chiral 3,4‐dihydroisoquinolin‐1(2H)‐one are included.

Cationic Iridium/Chiral Bisphosphine-Catalyzed Enantioselective Hydroacylation of Ketones.

A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine-catalyzed asymmetric intramolecular carbonyl hydroacylation of 2-keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium-labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the C-H activation step is not included in the turnover-limiting step.

Oxidative Addition Promoted C–C Bond Cleavage in Rh-Mediated Cyclopropenone Activation: A DFT Study

Computational characterization of the oxidation addition promoted in rhodium-catalyzed cyclopropenone activation and conversion via quinolyl-, pyridyl-, and nitrone-directed C–H activation is presented. Our theoretical studies found that a common catalytic cycle for these reactions starts with Rh(III)-mediated concerted metalation–deprotonation or electrophilic deprotonation to afford the aryl-Rh(III) intermediate. Oxidative addition of cyclopropenone to aryl-Rh(III) then gives a cyclorhoda(V)butanone intermediate, leading to the cleavage of the cyclopropene moiety through a concerted three-membered cyclic transition state. Subsequent reductive elimination of the intermediate generates a target C(aryl)–C(acyl) bond. The final product is produced by further transformations with concomitant regeneration of active Rh(III) catalyst. The previously proposed carbonyl insertion mode for the activation of cyclopropenones is excluded by the density functional theory calculations. The directing group effect in cyclopropenone activation was theoretically investigated. Distortion–interaction analysis, noncovalent interaction analysis, and global electrophilicity/nucleophilicity index calculations reveal the lower oxidation addition reactivity with the nitrone directing group, which is coincident with experimental observations. Distortion–interaction analysis was also performed to reveal the regioselectivity of the oxidative addition with asymmetrical cyclopropenones.

Redox‐Neutral Coupling between Two C(sp3)−H Bonds Enabled by 1,4‐Palladium Shift for the Synthesis of Fused Heterocycles

AbstractThe intramolecular coupling of two C(sp3)−H bonds to forge a C(sp3)−C(sp3) bond is enabled by 1,4‐Pd shift from a trisubstituted aryl bromide. Contrary to most C(sp3)−C(sp3) cross‐dehydrogenative couplings, this reaction operates under redox‐neutral conditions, with the C−Br bond acting as an internal oxidant. Furthermore, it allows the coupling between two moderately acidic primary or secondary C−H bonds, which are adjacent to an oxygen or nitrogen atom on one side, and benzylic or adjacent to a carbonyl group on the other side. A variety of valuable fused heterocycles were obtained from easily accessibleortho‐bromophenol and aniline precursors. The second C−H bond cleavage was successfully replaced with carbonyl insertion to generate other types of C(sp3)‐C(sp3) bonds.

Redox-Neutral Coupling between Two C(sp3 )-H Bonds Enabled by 1,4-Palladium Shift for the Synthesis of Fused Heterocycles.

The intramolecular coupling of two C(sp3 )-H bonds to forge a C(sp3 )-C(sp3 ) bond is enabled by 1,4-Pd shift from a trisubstituted aryl bromide. Contrary to most C(sp3 )-C(sp3 ) cross-dehydrogenative couplings, this reaction operates under redox-neutral conditions, with the C-Br bond acting as an internal oxidant. Furthermore, it allows the coupling between two moderately acidic primary or secondary C-H bonds, which are adjacent to an oxygen or nitrogen atom on one side, and benzylic or adjacent to a carbonyl group on the other side. A variety of valuable fused heterocycles were obtained from easily accessible ortho-bromophenol and aniline precursors. The second C-H bond cleavage was successfully replaced with carbonyl insertion to generate other types of C(sp3 )-C(sp3 ) bonds.

Something special about CO-dependent CO2 fixation.

Carbon dioxide enters metabolism via six known CO 2 fixation pathways, of which only one is linear, exergonic in the direction of CO 2‐assimilation, and present in both bacterial and archaeal anaerobes – the Wood‐Ljungdahl (WL) or reductive acetyl‐CoA pathway. Carbon monoxide (CO) plays a central role in the WL pathway as an energy rich intermediate. Here, we scan the major biochemical reaction databases for reactions involving CO and CO 2. We identified 415 reactions corresponding to enzyme commission (EC) numbers involving CO 2, which are non‐randomly distributed across different biochemical pathways. Their taxonomic distribution, reversibility under physiological conditions, cofactors and prosthetic groups are summarized. In contrast to CO 2, only 15 reaction classes involving CO were detected. Closer inspection reveals that CO interfaces with metabolism and the carbon cycle at only two enzymes: anaerobic carbon monoxide dehydrogenase (CODH), a Ni‐ and Fe‐containing enzyme that generates CO for CO 2 fixation in the WL pathway, and aerobic CODH, a Mo‐ and Cu‐containing enzyme that oxidizes environmental CO as an electron source. The CO‐dependent reaction of the WL pathway involves carbonyl insertion into a methyl carbon‐nickel at the Ni‐Fe‐S A‐cluster of acetyl‐CoA synthase (ACS). It appears that no alternative mechanisms to the CO‐dependent reaction of ACS have evolved in nearly 4 billion years, indicating an ancient and mechanistically essential role for CO at the onset of metabolism.

DFT study on mechanism of carbonyl hydrosilylation catalyzed by high-valent molybdenum (IV) hydrides

Density functional theory (DFT) calculations have been employed to investigate hydrosilylation of carbonyl compounds catalyzed by three high-valent molybdenum (VI) hydrides: Mo(NAr)H(Cp)(PMe3) (1A), Mo(NAr)H(PMe3)3 (1B), and Mo(NAr)H (Tp)(PMe3) (Tp = tris(pyrazolyl) borate) (1C). Three independent mechanisms have been explored. The first mechanism is “carbonyl insertion pathway”, in which the carbonyls insert into Mo−H bond to give a metal alkoxide complex. The second mechanism is the “ionic hydrosilylation pathway”, in which the carbonyls nucleophilically attacks η1-silane molybdenum adduct. The third mechanism is [2 + 2] addition mechanism which was proposed to be favorable for the high-valent di-oxo molybdenum complex MoO2Cl2 catalyzing the hydrosilylation. Our studies have identified the “carbonyl insertion pathway” to be the preferable pathway for three molybdenum hydrides catalyzing hydrosilylation of carbonyls. For Mo(NAr)H (Tp)(PMe3) (Tp = tris(pyrazolyl) borate), the proposed nonhydride mechanism experimentally is calculated to be more than 32.6 kcal/mol higher than the “carbonyl insertion pathway”. Our calculation results have derived meaningful mechanistic insights for the high-valent transition metal complexes catalyzing the reduction reaction.

Decisive effects of solvent and substituent on the reactivity of Ru-catalyzed hydrogenation of ethyl benzoate to benzyl alcohol and ethanol: A DFT study

Density functional theory (DFT) calculations have been implemented to clarify the hydrogenation mechanism of a non-active ester: ethyl benzoate (PhCOOC2H5) to ethanol (C2H5OH) and benzyl alcohol (PhCH2OH) catalyzed by RuIIPNN. The calculated catalytic cycle involves two similar hydrogenation processes with the persistent participation of the catalyst: hydrogenation of PhCOOC2H5 to C2H5OH and intermediate PhCHO, and further hydrogenation to PhCH2OH. Three potential mechanisms, named as carbonyl insertion mechanism, stepwise double-hydrogen-transfer mechanism, and direct reduction mechanism, have been investigated in details in different solvents. It is found that the solvent has decisive influence on the hydrogenation mechanism. In a less polar solvent, the reaction prefers a stepwise double-hydrogen-transfer hydrogenation mechanism consisting of dihydrogen activation, stepwise double-hydrogen-transfer, and hydrogen abstraction rather than the carbonyl insertion mechanism proposed in the experimental work. However, in a more polar solvent, the reaction proceeds via the direct reduction mechanism involving the separated ions (PhCH(OC2H5)O− and monocation) instead of the experimentally proposed hemiacetal intermediate PhCH(OH)OC2H5. The dihydrogen activation as common starting point of the reaction in all three potential mechanisms can be facilitated by the products (C2H5OH and PhCH2OH). The substituent group on an ester has little influence on the reaction mechanism while it greatly affects the reactivity: the electron withdrawing group favors the hydrogenation, while the electron donating group makes the reaction more difficult. These theoretical results are expected to provide valuable guidance for the experimental study of the hydrogenation of non-active esters.

Novel dinuclear and trinuclear ruthenium clusters derived from 2‐aryl‐substituted indenylphosphines via C─H bond cleavage

Treatment of Ru3(CO)12 with an equivalent of (2‐phenyl‐1H‐inden‐3‐yl)dicyclohexylphosphine (1) and (2‐pyridyl‐1H‐inden‐1‐yl)dicyclohexylphosphine (4) in refluxing heptane gave the novel trinuclear ruthenium clusters (μ3‐η1:η2:η5–2‐phenyl‐3‐Cy2PC9H4)Ru3(CO)8 (1c) and [μ2‐η1–2‐(pyridin‐2‐yl)‐3‐Cy2PC9H6]Ru3(CO)9 (4a), respectively, via C─H bond cleavage. (2‐Mesityl‐1H‐inden‐3‐yl)dicyclohexylphosphine (2) reacted with Ru3(CO)12 in refluxing heptane to give the trinuclear ruthenium cluster [μ‐2‐mesityl‐(3‐Cy2PC9H5)](μ2‐CO)Ru3(CO)9 (2c) via C─H bond cleavage and carbonyl insertion. 2‐(Anthracen‐9‐yl)‐1H–inden‐3‐yldicyclohexylphosphine (3) reacted with Ru3(CO)12 in refluxing heptane to give the dinuclear ruthenium cluster [μ2‐η3:η3–2‐(anthracen‐9‐yl)‐3‐Cy2PC9H6]Ru2(CO)5 (3a). The structures of 1c, 2c, 3a and 4a were fully characterized using IR and NMR spectroscopy, elemental analysis and single‐crystal X‐ray diffraction. These results suggest that the 2‐aryl substituent on the indenyl ring has a pronounced effect on the reaction and coordination modes of Ru3(CO)12.

Mechanism of Rhodium-Catalyzed Formyl Activation: A Computational Study.

Metal-catalyzed transfer hydroformylation is an important way of cleaving C-C bonds and constructing new double bonds. The newly reported density functional theory (DFT) method, M11-L, has been used to clarify the mechanism of the rhodium-catalyzed transfer hydroformylation reported by Dong et al. DFT calculations depict a deformylation and formylation reaction pathway. The deformylation step involves an oxidative addition to the formyl C-H bond, deprotonation with a counterion, decarbonylation, and β-hydride elimination. After olefin exchange, the formylation step takes place via olefin insertion into the Rh-H bond, carbonyl insertion, and a final protonation with the conjugate acid of the counterion. Theoretical calculations indicate that the alkalinity of the counterion is important for this reaction because both deprotonation and protonation occur during the catalytic cycle. A theoretical study into the formyl acceptor shows that the driving force of the reaction is correlated with the stability of the unsaturated bond in the acceptor. Our computational results suggest that alkynes or ring-strained olefins could be used as formyl acceptors in this reaction.

Facile C–H, C–F, C–Cl, and C–C Activation by Oxatitanacyclobutene Complexes

Aryl ketones react readily with oxatitanacyclobutenes bearing pentamethylcyclopentadienyl ligands to form unique titanocene complexes resulting from Cp* modification and C–H activation. An intermediate in this reaction is intercepted with various functional groups to form carbonyl insertion, C–F activation, and cyclopropane ring-opening products.

Scope and Mechanistic Studies of the Cationic Ir/Me-BIPAM-Catalyzed Asymmetric Intramolecular Direct Hydroarylation Reaction

Results of mechanistic studies on asymmetric hydroarylation of α-keto amides via direct C–H bond addition to a carbonyl group catalyzed by a cationic Ir/Me-BIPAM complex are presented in this paper. A catalytic cycle involving C–H bond cleavage to give an Ar-[Ir]+ intermediate, insertion of a carbonyl group into the aryl-iridium bond, giving iridium alkoxide, and finally reductive elimination to reproduce active [Ir]+ species is proposed. The mechanistic insight for the iridium hydride species indicated that the C–H bond cleavage is caused in a reversible manner. Furthermore, the kinetic isotope effect was measured by product analysis of the reaction to compare H/D, and it was determined that kH/kD was 1.85. These experimental results suggest that the C–H bond cleavage step is not included in the turnover-limiting step. In addition, Hammett studies of substrates (ρ = −0.99) demonstrated that electron-donating groups at the para position to the reactive C–H bond accelerate the reaction rate. This linear relationship obtained in the Hammett plot indicates that the nucleophilicity of the aryl-iridium intermediate is an important factor in this reaction. All of the data indicate that carbonyl insertion into aryl-iridium is included in the turnover-limiting step of the catalytic cycle.

Theoretical studies of cobalt(I)-catalyzed hydroacylation of vinylsilanes and alkyl aldehydes

Density functional theory (DFT) was used to investigate computationally cobalt(I)-catalyzed hydroacylation of vinylsilanes and alkyl aldehydes to give ketones. Calculation indicated that cobalt(I)-catalyzed hydroacylation had eight possible reaction pathways. In the cobalt-hydride complexes IM2a and IM2b, the hydrogen migration occurred prior to the carbon–carbon bond-forming reaction. In the complexes IM3a1 and IM3b1, the carbonyl elimination reaction occurred prior to the direct reductive elimination reaction. In the cobalt–carbonyl complexes IM4a and IM4b, the carbonyl insertion reaction was much easier to achieve than the decarbonylation reaction. The dominant reaction pathway was the reaction channel IM1a TS1a IM2a TS2a1 IM3a1 TS4a IM4a TS5a IM5a TS6a IM6a, and the reductive elimination reaction was the rate-determining step for this channel, so the dominant product predicted theoretically was the linear ketone. Furthermore, the solvation effect was remarkable, and it decreased generally the free energies of the species. Copyright © 2015 John Wiley & Sons, Ltd.

Phosphine addition to the σ,π–thienyl complex [Fe2(CO)6(μ-Th)(μ-PTh2)] (Th = C4H3S): Carbonyl substitution and migratory carbonyl insertion to give the thienyl–acyl complexes [Fe2(CO)4(diphosphine)(μ-O[dbnd]C-Th)(μ-PTh2)

The reactivity of the σ,π–thienyl complex [Fe2(CO)6(μ-Th)(μ-PTh2)] (1) towards a range of phosphines has been studied. With PR3 (R=Ph, Th) carbonyl substitution affords [Fe2(CO)5(PR3)(μ-Th)(μ-PTh2)] (2a–b) as the major product, with smaller amounts of the thienyl–acyl complexes [Fe2(CO)5(PR3)(μ-OC-Th)(μ-PTh2)] (3a–b) resulting from a migratory carbonyl insertion into the thienyl ligand. With diphosphines, thienyl–acyl complexes are the major products in all cases. With dppm, [Fe2(CO)4(μ-dppm)(μ-OC-Th)(μ-PTh2)] (4) results in which the diphosphine bridges the iron–iron bond, while with other diphosphines the chelate complexes [Fe2(CO)4(κ2-diphosphine)(μ-OC-Th)(μ-PTh2)] (5–9) are isolated, as established through crystallographic studies on [Fe2(CO)4(κ2-dppe)(μ-OC-Th)(μ-PTh2)] (5) and [Fe2(CO)4(κ2-dppb)(μ-OC-Th)(μ-PTh2)] (9), both of which show that the diphosphine binds selectively to the oxygen-bound metal centre with phosphorus atoms lying trans to the metal–metal bond and μ-PTh2 bridge. With 1,2-bis(diphenylphosphino)benzene (dppb), [Fe2(CO)5{μ,κ2-C6H4PPh(C6H4)PPh2}(μ-PTh2)] (10) is isolated in low yields and results from cyclometalation of a phenyl ring and putative elimination of thiophene. In a separate experiment, it has been shown that heating 9 results in the slow formation of 10.

Alkoxycarbonylpiperidines as N-nucleophiles in the palladium-catalyzed aminocarbonylation

Piperidines possessing ester functionality, such as 2-(methoxycarbonyl)piperidine (methyl pipecolinate), 3-(ethoxycarbonyl)piperidine (ethyl nipecotate), and 4-(ethoxycarbonyl)piperidine (ethyl isonipecotate), were used as N-nucleophiles in palladium-catalyzed aminocarbonylation of iodobenzene and iodoalkenes such as 1-iodocyclohexene and 17-iodoandrost-16-ene. While the aminocarbonylation of both iodoalkenes, carried out under mild reaction conditions, resulted in the exclusive formation of the carboxamide, the same reaction of iodobenzene brought about the mixture of the corresponding carboxamide and 2-ketocarboxamide. The chemoselectivity toward the latter compounds, formed via double carbonyl insertion, was substantially increased by using high carbon monoxide pressure (up to 40 bar). Carboxamides derived from iodoalkenes and ketocarboxamides derived from iodoarene have been obtained in moderate to high yields.

Synthesis of Multicyclic Heterocycles Initiated by C–H Bond Activation Along with “Rollover” Using a Rh(III) Catalyst

ABSTRACTVarious multicyclic heterocycles were synthesized via “rollover” as the key pathway using a Rh(III) catalyst with a catalytic amount of sodium pivalate or copper(II) acetate. 3‐Alkynyl‐2‐heteroarylpyridines were transformed into tri‐ or tetracyclic heterocycles containing two heteroatoms via an intramolecular alkyne insertion. 3‐Aryloyl‐2‐arylpyridines were derived into 4‐azafluoren‐9‐ols via the intramolecular carbonyl insertion.

Adaptable synthesis of C-lactosyl glycoclusters and their binding properties with galectin-3.

We report here the syntheses of mono- to tetravalent glycoclusters containing 1-methylene-C-β-lactose. The 1-methylene-C-β-lactose moiety has been synthesized from octa-acetyl-β-lactose using the key carbonyl insertion reaction and linked to a series of alkynlated scaffolds via CuAAC reaction to afford mono- to tetravalent glycoclusters. The binding affinities of the final products to galectin-3 were found in the range of 10-100 μM.

Reactions of the σ,π-furyl complex [Fe2(CO)6(μ-Fu)(μ-PFu2)] (Fu = C4H3O) with phosphines: Carbonyl substitution, migratory carbonyl insertion and cyclometallation-induced furan elimination

The reactivity of the σ,π-furyl complex [Fe2(CO)6(μ-Fu)(μ-PFu2)] (1) towards PPh3 and a range of bidentate phosphines has been studied and a number of different reaction products have been identified. With PPh3, carbonyl substitution affords [Fe2(CO)5(PPh3)(μ-Fu)(μ-PFu2)] (2) in which the new phosphine is coordinated to the iron center that is σ-coordinated by the bridging furyl moiety. With small bite-angle diphosphines – bis(diphenylphosphino)methane (dppm) and 1,8-bis(diphenylphosphino)naphthalene (dppn) – carbonyl substitution and migratory carbonyl insertion result to give the furyl–acyl complexes with bridging, [Fe2(CO)4(μ-dppm)(μ-OCFu)(μ-PFu2)] (3), or chelating, [Fe2(CO)4(κ2-dppn)(μ-OC–Fu)(μ-PFu2)] (4), diphosphines, respectively. With the more flexible diphosphines Ph2P(CH2)nPPh2 (n = 2, dppe, n = 3, dppp), the cyclometallated products [Fe2(CO)5{μ,κ2-C6H4PPh(CH2)nPPh2}(μ-PFu2)] (n = 2, 5; n = 3, 6) are isolated as a result of carbonyl substitution and furan elimination, and a similar complex [Fe2(CO)5{μ,κ2-C6H4PPh(C6H4)PPh2}(μ-PFu2)] (7) is generated from the more rigid diphosphine bis(diphenylphosphino)benzene (dppb). With bis(diphenylphosphino)-1,1-binaphthalene (1,1-BINAP) the novel tridentate phosphine complex [Fe2(CO)5{μ,κ3-C6H4P(C20H12PPh2)C6H4PFu}] (8) results from the putative coupling of cyclometallated diphosphine and difurylphosphido ligands, following elimination of two equivalents of furan. The crystal structures of 2, 3, 5 and 8 have been determined and allow a detailed insight into the overall reaction profile.

ChemInform Abstract: Aminocarbonylation of (Hetero)aryl Bromides with Ammonia and Amines Using a Palladium/DalPhos Catalyst System.

AbstractAmmonia acts as both nucleophile and base in these reactions.