Carbonyl Insertion Research Articles

Aminocarbonylation of (Hetero)aryl Bromides with Ammonia and Amines using a Palladium/DalPhos Catalyst System

AbstractVariants of the DalPhos [2‐aminophenylbisadamantyl)phosphine] ligand family were examined in a palladium‐catalyzed carbonylative amination reaction using inexpensive carbon monoxide and ammonia as reagents. As a result of this survey, the Pyr‐DalPhos ligand was identified as being effective for the selective aminocarbonylation of aryl bromides with ammonia, as well as primary and secondary alkylamines. A variety of primary aromatic, heteroaromatic and N‐substituted benzamides were formed in moderate to good yields. As part of this study, a (Mor‐DalPhos)Pd‐benzoyl complex was prepared and crystallographically characterized, thereby showing the viability of the carbonyl insertion step.

Computational Mechanistic Study of the Hydrogenation of Carbonate to Methanol Catalyzed by the RuIIPNN Complex

Density functional theory computations have been carried out to study the mechanism of hydrogenation-based transformation of dimethyl carbonate to methanol, catalyzed by Ru(II)PNN catalyst. The energetic results show that the catalytic transformation includes three sequential stages consistently involving the catalyst: (stage I) transformation of dimethyl carbonate (3) to methyl formate (5) and methanol; (stage II) transformation of methyl formate 5 to formaldehyde and methanol; (stage III) hydrogenation of formaldehyde to methanol. Stages I and II proceed similarly and follow three steps: hydrogen activation, formation of a hemiacetal intermediate via stepwise hydrogen transfer to dimethyl carbonate in stage I or methyl fomate in stage II, and subsequent decomposition of the hemiacetal intermediate to afford methanol. Hydrogenation via carbonyl insertion into the Ru-H bond is less favorable than the stepwise hydrogen-transfer mechanism. Decomposition of hemiacetal takes places by first breaking the hemiacetal O-H bond to give an alkoxide complex, followed by deprotonation of the benzylic arm ligand to the adjacent methoxy group. Comparing the hydrogenation steps in the three stages, hydrogenation in stage I is most difficult, that in stage II is less difficult, and that in stage III is easiest in terms of both kinetics and thermodynamics. This can be ascribed to the stronger electrophilicity of the carbonyl group in methyl formate or formaldehyde than that in dimethyl carbonate and fewer steric effects between the catalyst and methyl formate or formaldehyde than that between the catalyst and dimethyl carbonate. Thermodynamically, both stages I and II are uphill, but stage III is downhill significantly, which is the driving force for the catalytic transformation. The study indicates that the methanol product could facilitate the hydrogen activation involved in the transformation, implying that transformation could be accelerated by initially adding methanol.

Theoretical studies on the Mo-catalyzed asymmetric intramolecular Pauson-Khand-type [2 + 2 + 1] cycloadditions of 3-allyloxy-1-propynylphosphonates

Density functional theory (DFT) was used to investigate the Mo-catalyzed intramolecular Pauson-Khand reaction of 3-allyloxy-1-propynylphosphonates. All intermediates and transition states were optimized completely at the B3LYP/6-31 G(d,p) level [LANL2DZ(f) for Mo]. In the Mo-catalyzed intramolecular Pauson-Khand reaction, the C–C oxidative cyclization reaction was the chirality-determining step, and the reductive elimination reaction was the rate-determining step. The carbonyl insertion reaction into the Mo–C(sp(3)) bondwas easier than into the Mo–C=C bond. And the dominant product predicted theoretically was of (S)-chirality, which agreed with experimental data. This reaction was solventd ependent, and toluene was the best among the three solvents toluene, CH3CN, and THF.

Oxidative addition of methyl iodide to [Rh(CH3COCHCOCH3)(CO)(P(OCH2)3CCH3)

The reaction rate of the oxidative addition and the following CO insertion step of methyl iodide with [Rh(acac)(CO)(P(OCH2)3CCH3)] is determined. The key finding is that while [Rh(acac)(CO)(P(OCH2)3CCH3)] oxidatively adds methyl iodide ca 300 times faster than the Monsanto catalyst, the CO insertion step is much slower. However, the rate-determining step of the oxidative addition reaction of the phosphorus-containing acetylacetonato-rhodium(I) complex, the carbonyl insertion step, is still in the same order or faster than the rate-determining oxidative addition step of iodomethane to [Rh(CO)2I2]−.

Nonhydride mechanism of metal-catalyzed hydrosilylation.

A 1:1:1 reaction between complex (Tp)(ArN═)Mo(H)(PMe(3)) (3), silane PhSiD(3), and carbonyl substrate established that hydrosilylation catalyzed by 3 is not accompanied by deuterium incorporation into the hydride position of the catalyst, thus ruling out the conventional hydride mechanism based on carbonyl insertion into the M-H bond. An analogous result was observed for the catalysis by (O═)(PhMe(2)SiO)Re(PPh(3))(2)(I)(H) and (Ph(3)PCuH)(6).

Methyl iodide oxidative addition to [Rh(acac)(CO)(PPh3)]: an experimental and theoretical study of the stereochemistry of the products and the reaction mechanism

Density functional theory was used to investigate the oxidative addition and subsequent carbonyl insertion and deinsertion steps of the reaction of methyl iodide to a rhodium(I) acetylacetonato complex of the formula [Rh(acac)(CO)(PPh(3))] (Hacac = acetylacetone). This process has been studied experimentally for many rhodium β-diketonato complexes, but, to the best of our knowledge, this is the first systematic computational study of the complete reaction sequence. Experimental (1)H techniques complement the theoretical results on the stereochemistry of the reaction intermediates and products. (1)H NMR also revealed the existence of a second rhodium(III)-acyl product, which has not been previously observed in this reaction. The calculated Gibbs free energy of activation of the oxidative addition reaction is 71 kJ mol(-1), which is in agreement with the experimental value of 82(1) kJ mol(-1). The DFT-calculated oxidative addition corresponds to an associative S(N)2 nucleophilic attack by the rhodium metal centre on the methyl iodide, which is in agreement with calculated and experimental (in brackets) activation parameters of the reaction, 27 (38.8) kJ mol(-1) for ΔH((≠)) and -147 (-146) J K(-1) mol(-1) for ΔS((≠)).

ChemInform Abstract: [11C]Phosgene, a Versatile Reagent for Radioactive Carbonyl Insertion into Medicinal Radiotracers for Positron Emission Tomography

AbstractReview: 107 refs.

Reactivity of Paramagnetic FeII–Bis(amidinate) Complexes

AbstractSynthesis and characterisation of ether adducts of bis(amidinate) FeII complexes are described [amidinate = 2,6‐iPr2C6H3–NC(Ph)N–Ph]. The isolation of these five‐coordinate complexes contrasts with the homoleptic bis(amidinate) Fe complexes obtained previously with the sterically more demanding amidinate ligands 2,6‐iPr2C6H3–NC(Ph)N–Ar (Ar = 2,6‐iPr2C6H3, 2,6‐Me2C6H3) The more accessible ether adducts show enhanced reactivity towards Lewis bases and towards the π‐acid carbon monoxide. Reaction with excess amounts of CO results in carbonyl insertion into the Fe–N bonds, thereby giving rise to a diamagnetic bis(CO) adduct supported by two carbamoyl ligands.

11C]Phosgene: A Versatile Reagent for Radioactive Carbonyl Insertion Into Medicinal Radiotracers for Positron Emission Tomography

[¹¹C]Phosgene has been playing a relatively modest but continuous and manifest role all along the history of radiochemistry for Positron Emission Tomography. It acts as a radiolabelling agent through carbonyl insertion, usually between heteroatoms, and benefits from a high chemical reactivity allowing for short reaction times. The aim of this review is to give an overview of this radiochemistry from its beginning until the present day. After drawing up the inventory of the various ways of its production, the reactions in which it has been employed and the labelled products that have been synthesised with it are catalogued. This comprises the reactions of [¹¹C]phosgene with primary, secondary and tertiary amines to labelled isocyanates and carbamoyl chlorides, which serve as intermediates for symmetrical and unsymmetrical [¹¹C]ureas and [¹¹C]carbamates, reactions with alcohols leading to labelled carbamates and carbonates via [¹¹C]chloroformates, cyclisation reactions to heterocycles and the radiochemistry of the secondary radiolabelling agents [¹¹C]urea and diethyl- or dimethyl [¹¹C]carbonate. Apart from this already vast field of chemical possibilities there should be room for extension of the use of [¹¹C]phosgene to other chemistry, notably that of C-¹¹C bond formation.

ChemInform Abstract: Hydrozirconation of (E)-3-Methoxy-1-phenyl-1-propene and (E)-3-Phenyl- 2-propenol.

Abstract Hydrozirconation-deuterolysis of ( E )-3-methoxy-1-phenyl-1-propene was found to give α- and ω-deuterated propylbenzenes after elimination of the ether function. An unforeseen higher degree of benzylic substitution in the propylbenzenes was observed. In an effort to account for the regiochemical outcome of the reaction, hydrozirconation of propenylbenzenes with mixed reagents and deuterozirconation was investigated. Hydrozirconation of ( E )-3-propenol-2-propenol results in loss of the hydroxyl group to only a small extent, and after hydrozirconation and deuterolysis fair yields of benzenopropan-γ- d -ol are formed. Carbonyl insertion into 3-hydroxyl-1-phenyl-1-zirconocene-propane gives low yields of the lactone dihydro-3-phenyl-2(3 H )-furanone.

ChemInform Abstract: Highly Chemoselective α-Diazo Carbonyl Insertion Reactions into N-H and S-H Bonds Catalyzed by [RuCl(η5-C5H5) (PPh3)2

ChemInform Abstract: Highly Chemoselective α-Diazo Carbonyl Insertion Reactions into N-H and S-H Bonds Catalyzed by [RuCl(η5-C5H5) (PPh3)2

ESI-MS, DFT, and Synthetic Studies on the H2-Mediated Coupling of Acetylene: Insertion of C═X Bonds into Rhodacyclopentadienes and Brønsted Acid Cocatalyzed Hydrogenolysis of Organorhodium Intermediates

The catalytic mechanism of the hydrogen-mediated coupling of acetylene to carbonyl compounds and imines has been examined using three techniques: (a) ESI-MS and ESI-CAD-MS analyses, (b) computational modeling, and (c) experiments wherein putative reactive intermediates are diverted to alternate reaction products. ESI-MS analysis of reaction mixtures from the hydrogen-mediated reductive coupling of acetylene to alpha-ketoesters or N-benzenesulfonyl aldimines corroborate a catalytic mechanism involving C horizontal lineX (X = O, NSO(2)Ph) insertion into a cationic rhodacyclopentadiene obtained by way of acetylene oxidative dimerization with subsequent Brønsted acid cocatalyzed hydrogenolysis of the resulting oxa- or azarhodacycloheptadiene. Hydrogenation of 1,6-diynes in the presence of alpha-ketoesters provides analogous coupling products. ESI mass spectrometric analysis again corroborates a catalytic mechanism involving carbonyl insertion into a cationic rhodacyclopentadiene. For all ESI-MS experiments, the structural assignments of ions are supported by multistage collisional activated dissociation (CAD) analyses. Further support for the proposed catalytic mechanism derives from experiments aimed at the interception of putative reactive intermediates and their diversion to alternate reaction products. For example, rhodium-catalyzed coupling of acetylene to an aldehyde in the absence of hydrogen or Brønsted acid cocatalyst provides the corresponding (Z)-butadienyl ketone, which arises from beta-hydride elimination of the proposed oxarhodacycloheptadiene intermediate, as corroborated by isotopic labeling. Additionally, the putative rhodacyclopentadiene intermediate obtained from the oxidative coupling of acetylene is diverted to the product of reductive [2 + 2 + 2] cycloaddition when N-p-toluenesulfonyl-dehydroalanine ethyl ester is used as the coupling partner. The mechanism of this transformation also is corroborated by isotopic labeling. Computer model studies based on density functional theory (DFT) support the proposed mechanism and identify Brønsted acid cocatalyst assisted hydrogenolysis to be the most difficult step. The collective studies provide new insight into the reactivity of cationic rhodacyclopentadienes, which should facilitate the design of related rhodium-catalyzed C-C couplings.

On the Mechanism of the Palladium Catalyzed Intramolecular Pauson−Khand-Type Reaction

Density functional theory calculations and experimental studies have been carried out on the intramolecular Pauson-Khand-Type reaction mediated by a PdCl(2)-thiourea catalyst, which proceeds under mild reaction conditions and provides a useful alternative to traditional Pauson-Khand reactions. The classical mechanism of the Pauson-Khand reaction involving the alkyne/alkene C-C bond formation as the key step has been found to be energetically unfavorable and is not in line with the experimental observations. A novel reaction mechanism has been proposed for the reaction. The first step involves the cis-halometalation of the alkyne, followed by sequential alkene and carbonyl insertion. The rate-determining fourth step is an intramolecular C-Cl oxidative addition, leading to a Pd(IV) intermediate. A C-C bond formation by reductive elimination completes the reaction. The mechanism is in agreement with the key experimental observations including (1) the need of a chloride for catalytic activity and the absence of catalysis with Pd(OAc)(2) alone; (2) the rate acceleration by the addition of LiCl; both with PdCl(2) and Pd(OAc)(2) catalysts; and (3) the preferred formation of the trans diastereomer in substituted cases. The cis halometalation and the formation and stability of the Pd(IV) intermediate is studied in detail and provides general insights into these novel steps.

Oxidative Addition of CH3I and CO Migratory Insertion in a Series of Ferrocene-Containing Carbonyl Phosphine β-Diketonato Rhodium(I) Complexes

A kinetic study of the oxidative addition reaction between CH3I and a series of ferrocene-containing β-diketonato carbonyl phosphine rhodium(I) complexes [Rh(FcCOCHCOR)(CO)(PPh3)], with R = CF3 (1), CH3 (2), Ph = phenyl (3), and Fc = ferrocenyl (4), showed that the mechanism consists of three definite sets of reactions involving isomers of at least two distinctly different classes of RhIII-alkyl and two different classes of RhIII-acyl species. The first reaction set involves oxidative addition itself, while the second and third reaction sets lead to different isomerization products involving carbonyl insertion or deinsertion in the Rh-CH3 or Rh-COCH3 bond. Second-order rate constants for the first oxidative addition step in CHCl3 at 25 °C were ki = 0.0061(1), 0.065(1), 0.077(2), and 0.16(1) dm3 mol−1 s−1 for 1, 2, 3, and 4, respectively. The latter is the fastest reaction of this type reported to date for any [Rh(β-diketonato)(CO)(PPh3)] complex. Activation parameters for all reactions from a variable tem...

Theoretical Study on Mechanism of Hydroformylation of Ethene Catalyzed by a Heterobimetallic Rh(I)‐Cr Complex

Abstract The mechanism of ethene hydroformylation catalyzed by a heterobimetallic complex HRh(CO)(PH3)(µ‐PH2)2‐ Cr(CO)4 was investigated by density functional theory (DFT). Both the associative and dissociative mechanisms were studied, and the results were compared. It was found that the introduction of Cr(CO)4 moiety did not remodel the mechanism of hydroformylation of simple alkenes. The dissociative mechanism is predominant. The carbonyl insertion is the rate‐limiting step for the whole catalytic cycle with a free energy barrier of 91.15 kJ/mol at 298.15 K and 101.325 kPa. The aldehyde elimination step was predicted to be irreversible. These results are in good agreement with the previous theoretical and experimental studies.

Carbonylation of Aryl Halides: Extending the Scope of the Reaction

Carbonylation reactions are being increasingly favoured in pharmaceutical chemistry for the atom-efficient introduction of carbonyl centres in aldehydes, acids, esters, and amides. Convenient procedures for simple aryl iodides and bromides are well established, and now the need is to develop improved conditions to allow the reactions to be extended to the more unreactive substrates, such as sterically hindered compounds and aryl chlorides. Sterically hindered compounds such as 2-iodo- or 2-bromo-m-xylenes can be converted using alkoxy and aminocarbonylation, while dehalogenation becomes a significant side reaction for reductive carbonylation. Less hindered compounds such as 2-iodo- or bromotoluene can be reacted successfully. Changing the aryl ligands of PdCl2{Ph2P(CH2)3PPh2} to alkyl groups improves the rate of oxidative addition but slows the carbonyl insertion step such that rates for the majority of aryl bromides are not improved by this change. Complexes such as PdCl2{Cy2P(CH2)3PCy2} offer better performance for alkoxy and aminocarbonylation of aryl chlorides. However, for reductive carbonylation dehalogenation is a significant side reaction. Increasing CO pressure results in additional CO coordination to the catalytic intermediates and slows the reaction, while the dehalogenation is little affected, so reaction selectivity suffers. Thus, CO pressure is a critical parameter, particularly for reductive carbonylation, in achieving the optimum performance.

Dichalcogenide Cleavage and Carbonyl Insertion Reactions on a Dirhodium Bond

AbstractThe reaction of the binuclear rhodium complex [(η−C5H5)2Rh2(μ‐CO)(μ‐η1:η1‐C2(CF3)2)] with a series of dichalcogenides, R2E2 (E = S, Se, Te; R = Me, Et, i‐Pr, Ph, Fc; not all combinations) has provided mixtures of complexes, the majority of which have been characterized by standard spectroscopic techniques. These complexes arise as a consequence of carbonyl substitution followed by chalcogen‐chalcogen bond cleavage giving [(η−C5H5)2Rh2(μ‐ER)2(μ‐η1:η1‐C2(CF3)2)], possibly concomitant with CO insertion into a Rh‐C2(CF3)2 bond of the product in some cases, giving [(η−C5H5)2Rh2(CO)(μ‐ER)2(μ‐η1:η1‐C2(CF3)2C(O))] (E = Se, Te; R = Me, Et, i‐Pr, Ph, Fc; not all combinations). In the case of Te2R2 the dichalcogenide products have been structurally characterized for the carbonyl insertion product (for R = Et) and the simple cleavage case (for R = i‐Pr). In both, the putative m‐symmetry is broken by substituent dispositions and, in the R = Et adduct, torsion in the fluorocarbon skeleton.

Catalytic Carbonyl (Z)‐Dienylation via Multicomponent Reductive Coupling of Acetylene to Aldehydes and α‐Ketoesters Mediated by Hydrogen: Carbonyl Insertion into Cationic Rhodacyclopentadienes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Gene expression profiling in lung tissues from rats exposed to formaldehyde

Formaldehyde is a ubiquitous toxic organic compound recently classified as a carcinogen by the International Agency for Research on Cancer and one of the major factors causing sick building syndrome. In this study, we have investigated the effects of formaldehyde on mRNA expression in rat lung tissues by applying genomics. Rats were exposed to ambient air and two different concentrations of formaldehyde (0, 5, 10 ppm) for 2 weeks at 6 h/day and 5 days/week in an inhalation chamber. Malondialdehyde (MDA) assay and carbonyl spectrometric assay were conducted to determine lipid peroxidation and protein oxidation levels and Comet assays were used for genotoxicity evaluation. Level of MDA, carbonyl insertion and DNA damage in the lungs of rats exposed to FA were found to be dose dependently increased. Gene expression was evaluated by using a bio-array hybridization analysis. A total of 21 (2 up- and 19 down-regulated) genes were identified as biomarkers for formaldehyde effects. Several differentiated gene groups were found. Genes involved in apoptosis, immunity, metabolism, signal transduction, transportation, coagulation and oncogenesis were found to be up- and down-regulated. Among these genes, the mRNA expressions of cytochrome P450, hydroxymethylbilane synthase, glutathione reductase, carbonic anhydrase 2, natriuretic peptide receptor 3, lysosomal associated protein transmembrane 5, regulator of G-protein signaling 3, olfactomedin related ER localized protein, and poly (ADP-ribose) polymerase-1 were confirmed by quantitative RT-PCR analysis. In summary, the MDA lipid peroxidation and the carbonyl protein oxidation assays showed that cytotoxic effects increased with increasing formaldehyde levels. Genomic analysis showed that 21 genes were up- or down-regulated. Of these genes, nine were confirmed by quantitative RT-PCR and could be potential biomarkers for human diseases associated with formaldehyde exposure.

Cyclopropyl Building Blocks for Organic Synthesis. Part 131. Palladium‐Catalyzed Bicyclization with Carbonyl Insertion of Alkenyl‐Tethered Propargyl Carbonates Towards a Scalable Synthesis of Various 2‐(Bicyclo[3.1.0]hex‐1‐yl)acrylates.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.