Decarbonylation Of Aldehydes Research Articles

Regioselective Aldehyde Decarbonylation through Palladium-Catalyzed Nitrile Boronic Acid Cross-Coupling

AbstractAldehyde decarbonylation is a vital chemical transformation in the synthesis of natural products. Nature accomplishes this process through a family of decarbonylase enzymes, while in the laboratory, harsh transition metals and elevated temperatures are required. Herein, we report a mild aldehyde decarbonylation reaction that exhibits exclusive selectivity for ortho-aldehydes during a tandem nitrile boronic acid cross-coupling reaction. A wide substrate scope is displayed that includes regioselective removal of the ortho-aldehyde from phenyl boronic acids in the presence of meta- or para-aldehydes. A mechanistic investigation of the observed regioselectivity for ortho-aldehydes by density functional theory (DFT) calculations shows that the CO ligand extrusion is energetically more favorable for the ortho position as compared to the para position.

Photothermally induced decarbonylative C[sbnd]H arylation of arenes with aldehydes

Here, by using eosin Y as a preferable catalyst, we present a photothermally induced decarbonylative aryl CH arylation with the aldehydes. This transformation proceeds with operational simplicity and solvent-free conditions, does not need for 1,2-dinitrobenzene additive, and tolerates unsuccessful functionalities (e.g., 4-pyridine, NO2 and SO2Me) in previously reported protocols. In addition to the aryl aldehydes, the alkyl ones are also compatible with this transformation. Mechanistic investigations reveal that the reaction undergoes aldehyde decarbonylation to afford aryl radicals in situ, its regioselective addition to the arenes followed by single electron oxidation and homolytic hydrogen abstraction gives rise to the desired cross-coupling products. Give the striking features, this work offers a useful platform to directly access various biaryls.

Ligand enabled none-oxidative decarbonylation of aliphatic aldehydes

Decarbonylation of aldehydes is a basic organic transformation, which has been developed for more than six-decade. However, as comparing to well-studied aromatic aldehydes, fewer examples for catalytic decarbonylation of aliphatic aldehydes were reported, mainly on simple or special substrates. For α-bulky or highly functionalized ones, stoichiometric Rh(I) were usually required for decent yields. Herein, we present a rare example of Ir(I)-catalyzed direct decarbonylation of α-quaternary aldehydes with broad substrate scope and good functional group compatibility via judicious selection of ligand. The α-chirality is memorized in this decarbonylation process. In addition, we report a broad-spectrum decarbonylation of α-secondary and α-tertiary aldehydes containing multifunctional groups with an improved Rh(I)/DPPP recipe. Finally, we realized selective decarbonylation of α-tertiary aldehydes in the presence of α-quaternary one via the reactivity differences.

Utilizing Alcohol for Alkane Biosynthesis by Introducing a Fatty Alcohol Dehydrogenase.

Alkanes produced by microorganisms are expected to be an alternative to fossil fuels as an energy source. Microbial synthesis of alkanes involves the formation of fatty aldehydes via fatty acyl coenzyme A (acyl-CoA) intermediates derived from fatty acid metabolism, followed by aldehyde decarbonylation to generate alkanes. Advancements in metabolic engineering have enabled the construction of such pathways in various microorganisms, including Escherichia coli. However, endogenous aldehyde reductases in the host microorganisms are highly active in converting fatty aldehydes to fatty alcohols, limiting the substrate pool for alkane production. To reuse the alcohol by-product, a screening of fatty alcohol-assimilating microorganisms was conducted, and a bacterial strain, Pantoea sp. strain 7-4, was found to convert 1-tetradecanol to tetradecanal. From this strain, an alcohol dehydrogenase, PsADH, was purified and found to be involved in 1-tetradecanol-oxidizing reaction. Subsequent heterologous expression of the PsADH gene in E. coli was conducted, and recombinant PsADH was purified for a series of biochemical characterizations, including cofactors, optimal reaction conditions, and kinetic parameters. Furthermore, direct alkane production from alcohol was achieved in E. coli by coexpressing PsADH with a cyanobacterial aldehyde-deformylating oxygenase and a reducing system, including ferredoxin and ferredoxin reductase, from Nostoc punctiforme PCC73102. The alcohol-aldehyde-alkane synthetic route established in this study will provide a new approach to utilizing fatty alcohols for the production of alkane biofuel. IMPORTANCE Alcohol dehydrogenases are a group of enzymes found in many organisms. Unfortunately, studies on these enzymes mainly focus on their activities toward short-chain alcohols. In this study, we discovered an alcohol dehydrogenase, PsADH, from the bacterium Pantoea sp. 7-4, which can oxidize 1-tetradecanol to tetradecanal. The medium-chain aldehyde products generated by this enzyme can serve as the substrate of aldehyde-deformylating oxygenase to produce alkanes. The enzyme found in this study can be applied to the biosynthetic pathway involving the formation of medium-chain aldehydes to produce alkanes and other valuable compounds.

Rhodium-Catalyzed Deuterated Tsuji-Wilkinson Decarbonylation of Aldehydes with Deuterium Oxide.

The recent surge in the applications of deuterated drug candidates has rendered an urgent need for diverse deuterium labeling techniques. Herein, an efficient Rh-catalyzed deuterated Tsuji-Wilkinson decarbonylation of naturally available aldehydes with D2O is developed. In this reaction, D2O not only acts as a deuterated reagent and solvent but also promotes Rh-catalyzed decarbonylation. In addition, decarbonylative strategies for the synthesis of terminal monodeuterated alkenes from α,β-unsaturated aldehydes are within reach.

NHC‐Organocatalysed Hydroacylation of Unactivated or Weakly Activated C−C Multiple Bonds and Ketones

AbstractN‐Heterocyclic Carbenes (NHCs) are versatile organocatalysts owing to their umpolung capability – i. e. the catalytic transformation of electrophilic aldehydes into nucleophilic species. Profoundly, aldehyde umpolungs were exploited in Benzoin and Stetter reactions, whereas hydroacylation of unactivated carbon‐carbon multiple bonds (alkenes and alkynes) are challenging and highly desired. Normally, catalytic hydroacylation of alkenes was achieved by transition metal catalysts based on rhodium, cobalt, nickel, ruthenium, and iridium. However, the metal‐catalyzed strategy is accompanied by undesired side reactions, such as decarbonylation of aldehydes, and thus demands installation of directing group in the aldehydes. In contrast, NHCs overcome these downsides and utilize the umpolung strategy beyond the Benzoin and Stetter reactions to implement catalytic hydroacylation of unpolarised and unactivated carbon‐carbon multiple bonds (alkenes and alkynes) under mild reaction conditions with step‐ and atom‐economy. In addition, this unconventional transformation is extended to catalytic asymmetric catalysis. This highlight covers the progress and practicality of NHC‐catalyzed hydroacylation of alkenes, alkynes, arynes, and ketones to access biologically relevant organics. Both inter‐and intramolecular hydroacylation reactions in combination with Stetter were presented and key mechanistic pathways were discussed.

Decarbonylation of Aldehydes Catalyzed by Ceria-Supported Nickel Nanoparticles

Key words nickel catalysis - ceria - decarbonylation - aldehydes - nanoparticles

Cationic Iridium-Catalyzed Asymmetric Decarbonylative Aryl Addition of Aromatic Aldehydes to Bicyclic Alkenes.

Invited for the cover of this issue are Tomohiko Shirai and co-workers at the National Institute of Technology Kochi College and their collaborators at Chuo and Hokkaido Universities. The image depicts how asymmetric decarbonylative C-C bond formation by the Ir/S-Me-BIPAM complex takes precedence over aldehyde decarbonylation. Read the full text of the article at 10.1002/chem.202104347.

Cationic Iridium-Catalyzed Asymmetric Decarbonylative Aryl Addition of Aromatic Aldehydes to Bicyclic Alkenes.

We report an unprecedented catalytic protocol for the enantioselective decarbonylative transformation of aryl aldehydes. In this process, the decarbonylation of aldehydes catalyzed by chiral iridium complexes enabled the formation of asymmetric C-C bonds through the formation of an aryl-iridium intermediate. The decarbonylative aryl addition to bicyclic alkenes was fluidly performed without a stoichiometric aryl-metal reagent, such as aryl boronic acid, with a cationic iridium complex generated in situ from Ir(cod)2 (BArF 4 ) and the sulfur-linked bis(phosphoramidite) ligand ((R,R)-S-Me-BIPAM). This reaction has broad functional group compatibility, and no waste is generated, except carbon monoxide.

Palladium on carbon in PEG-400/Cyclohexane: Recoverable and recyclable catalytic system for efficient decarbonylation of aldehydes

A simple methodology for the decarbonylation of aldehydes catalysed by commercially available palladium on carbon in a green two-solvent system is reported. Various aromatic, aliphatic and heteroaromatic aldehydes were transformed to the corresponding decarbonylated products in good yields. Product isolation from the reaction mixture is simple in practice, and the catalyst can be reused three times.

Bromo Radical‐Mediated Photoredox Aldehyde Decarbonylation towards Transition‐Metal‐Free Hydroalkylation of Acrylamides at Room Temperature

AbstractHerein, we report a visible‐light‐mediated hydroalkylation reaction of alkenes using easily available aldehydes as alkyl sources via bromo radical‐promoted photoredox decarbonylation. This protocol provides an alternative entry to C(sp3)−C(sp3) bond formation and features considerable advantages including mild and clean reaction conditions, obviation for transition‐metal catalyst, and good functional group compatibility.magnified image

Application of Transition Metal‐Catalyzed Decarbonylation of Aldehydes in the Total Synthesis of Natural Products

AbstractDecarbonylation is an invaluable reaction, utilized by nature and chemists alike. In different life forms, such as prokaryotes, plants and animals, this transformation is catalyzed by aldehyde decarbonylases. In the laboratory, the transition metal‐catalyzed (TMC) decarbonylation, which was first achieved in 1959, is by and large the dominant way for conducting this reaction. The carbon‐carbon bond cleavage is most often made possible by RhCl(PPh3)3 i. e. Wilkinson's catalyst, but other metals are also used, both in academia and in industry. In this review, we chose to present the applications of TMC decarbonylation in the synthesis of natural products and their derivatives. More than 30 examples are showcased and categorized into three categories based on the essence of the role of the aldehyde group in the synthesis. A short outlook is given in the end, listing the different advantages and disadvantages of Wilkinson's catalyst, as well as offering a brief prospect for the future.

Heterogeneously Catalyzed Selective Decarbonylation of Aldehydes by CeO2-Supported Highly Dispersed Non-Electron-Rich Ni(0) Nanospecies

Heterogeneously Catalyzed Selective Decarbonylation of Aldehydes by CeO₂-Supported Highly Dispersed Non-Electron-Rich Ni(0) Nanospecies

Photo-redox coupled Co-pincer complexes for efficient decarbonylation of aryl carbonyls: A quantum chemical investigation

Abstract Catalytic decarbonylation of aryl carbonyls is a challenging task. Although some precious metal based catalysts have been developed, Earth abundant transition metal based decarbonylating catalysts are yet to be realized. Very recently, Co(I) pincer complex has been utilized for one step decarbonylation of aromatic and aliphatic aldehydes, however, the reactions do not proceed for the next step catalytic cycle. To address this issue, we here present the thermodynamic and mechanistic aspects of the reactions and on the basis of first principles calculations, we shed some light for further developing the catalyst. We demonstrate that it is the thermodynamic factor that inhibits the catalytic activity due to very strong metal-carbonyl interactions. However, a similar Co(II) complex shows much less regeneration energy but fails to initiate the reaction. We propose that if a suitable Ru(II)/Ir(III) photo sensitizer is used, the resultant photoredox catalytic system coupled with the Co(II) pincer complex might be very efficient for the decarbonylation process.

TBHP/TBAI–Mediated simple and efficient synthesis of 3,5-disubstituted and 1,3,5-trisubstituted 1H-1,2,4-triazoles via oxidative decarbonylation of aromatic aldehydes and testing for antibacterial activities

The author has developed a simple, efficient and eco–friendly convenient general method for synthesis of 3,5–disubstituted–1,2,4–triazoles and 1,3,5–trisubstituted–1,2,4–triazoles from 3–monosubstituted–1,2,4–triazoles and 1,3–disubstituted–1,2,4–triazoles respectively using tetrabutylammonium iodide (TBAI) as catalyst and TBHP as oxidant under mid reaction conditions. This method provides structurally diverse 3,5–disubstituted 1,2,4–triazoes and 1,3,5––trisubstituted–1,2,4–triazoles in good to excellent yields. 3,5–Disubstituted 1,2,4–triazoes and 1,3,5––trisubstituted–1,2,4–triazoles derivatives are biologically and pharmaceutically active molecules, and therefore, this protocol could be of wide applications in medicinal chemistry and organic chemistry.

Iron-Catalyzed Cleavage Reaction of Keto Acids with Aliphatic Aldehydes for the Synthesis of Ketones and Ketone Esters.

The radical-radical coupling reaction is an important synthetic strategy. In this study, the iron-catalyzed radical-radical cross-coupling reaction based on the decarboxylation of keto acids and decarbonylation of aliphatic aldehydes to obtain valuable aryl ketones is reported for the first time. Remarkably, when tertiary aldehydes were used as carbonyl sources, ketone esters were selectively obtained instead of ketones. The gram-scale preparation of aryl ketone through this strategy was easily achieved by using only 3 mol % of the iron catalyst. As a proof-of-concept, the bioactive molecule flurprimidol was synthesized in two steps by using this strategy.

CO Gas-free Intramolecular Cyclocarbonylation Reactions of Haloarenes Having a C-Nucleophile through CO-Relay between Rhodium and Palladium.

We describe transfer carbonylation reactions of 2-bromoarenes that contain a carbon-nucleophile using aldehydes as a substitute for CO, leading to the formation of indanone derivatives. The transformation proceeds efficiently under RhI /Pd0 -hybrid catalytic conditions consisting of two discrete transition metals, rhodium and palladium, which catalyze the decarbonylation of aldehydes and the subsequent carbonylation of bromoarenes using the resulting carbonyl moiety, respectively. The majority of the abstracted CO is transferred directly to the product via a CO-relay process from rhodium to palladium.

Microwave-Assisted Decarbonylation of Biomass-Derived Aldehydes using Pd-Doped Hydrotalcites.

Catalytic decarbonylation is an underexplored strategy for deoxygenation of biomass-derived aldehydes owing to a lack of low-cost and robust heterogeneous catalysts that can operate in benign solvents. A family of Pd-functionalized hydrotalcites (Pd-HTs) were synthesized, characterized, and applied to the decarbonylation of furfural, 5-hydroxymethylfurfural (HMF), and aromatic and aliphatic aldehydes under microwave conditions. This catalytic system delivered enhanced decarbonylation yields and turnover frequencies, even at a low Pd loading (0.5 mol %). Furfural decarbonylation was optimized in a benign solvent (ethanol) compatible with biomass processing; HMF selectively afforded an excellent yield (93 %) of furfuryl alcohol without humin formation; however, a longer reaction favored the formation of furan through tandem alcohol dehydrogenation and decarbonylation. Yields of the substituted benzaldehydes (37-99 %) were proportional to the calculated Mulliken charge of the carbonyl carbon. Activity and selectivity reflected loading-dependent Pd speciation. Continuous-flow testing of the best Pd-HT catalyst delivered good stability over 16 h on stream, with near-quantitative conversion of HMF.

Drop-in biofuel production using fatty acid photodecarboxylase from Chlorella variabilis in the oleaginous yeast Yarrowia lipolytica

BackgroundOleaginous yeasts are potent hosts for the renewable production of lipids and harbor great potential for derived products, such as biofuels. Several promising processes have been described that produce hydrocarbon drop-in biofuels based on fatty acid decarboxylation and fatty aldehyde decarbonylation. Unfortunately, besides fatty aldehyde toxicity and high reactivity, the most investigated enzyme, aldehyde-deformylating oxygenase, shows unfavorable catalytic properties which hindered high yields in previous metabolic engineering approaches.ResultsTo demonstrate an alternative alkane production pathway for oleaginous yeasts, we describe the production of diesel-like, odd-chain alkanes and alkenes, by heterologously expressing a recently discovered light-driven oxidase from Chlorella variabilis (CvFAP) in Yarrowia lipolytica. Initial experiments showed that only strains engineered to have an increased pool of free fatty acids were susceptible to sufficient decarboxylation. Providing these strains with glucose and light in a synthetic medium resulted in titers of 10.9 mg/L of hydrocarbons. Using custom 3D printed labware for lighting bioreactors, and an automated pulsed glycerol fed-batch strategy, intracellular titers of 58.7 mg/L were achieved. The production of odd-numbered alkanes and alkenes with a length of 17 and 15 carbons shown in previous studies could be confirmed.ConclusionsOleaginous yeasts such as Yarrowia lipolytica can transform renewable resources such as glycerol into fatty acids and lipids. By heterologously expressing a fatty acid photodecarboxylase from the algae Chlorella variabilis hydrocarbons were produced in several scales from microwell plate to 400 mL bioreactors. The lighting turned out to be a crucial factor in terms of growth and hydrocarbon production, therefore, the evaluation of different conditions was an important step towards a tailor-made process. In general, the developed bioprocess shows a route to the renewable production of hydrocarbons for a variety of applications ranging from being substrates for further enzymatic or chemical modification or as a drop-in biofuel blend.

Decarbonylation through Aldehydic C–H Bond Cleavage by a Cationic Iridium Catalyst

We report the decarbonylation of aldehydes through an aldehydic C–H bond cleavage catalyzed by a cationic iridium/bisphosphine catalyst. The reaction proceeds under relatively mild conditions to give the corresponding hydrocarbon products in moderate to high yields. In addition, this cationic iridium catalyst system can be applied to an asymmetric hydroacylation of ketones.