Palladium-catalyzed Alkylation Research Articles

Palladium-Catalyzed Alkylation and Dienylation of Propargylic Carbonates with Hydrazones through Carbonyl Umpolung

Palladium-Catalyzed Alkylation and Dienylation of Propargylic Carbonates with Hydrazones through Carbonyl Umpolung

Enantioconvergent Palladium-Catalyzed Alkylation of Tertiary Allylic C-H Bonds.

Enantioconvergent catalysis enables the conversion of racemic molecules into a single enantiomer in perfect yield and is considered an ideal approach for asymmetric synthesis. Despite remarkable advances in this field, enantioconvergent transformations of inert tertiary C-H bonds remain largely unexplored due to the high bond dissociation energy and the surrounding steric repulsion that pose unparalleled constraints on bond cleavage and formation. Here, we report an enantioconvergent Pd-catalyzed alkylation of racemic tertiary allylic C-H bonds of α-alkenes, providing a unique approach to access a broad range of enantioenriched γ,δ-unsaturated carbonyl compounds featuring quaternary carbon stereocenters. Mechanistic studies reveal that a stereoablative event occurs through the rate-limiting cleavage of tertiary allylic C-H bonds to generate σ-allyl-Pd species, and the achieved E/Z-selectivity of σ-allyl-Pd species effectively regulates the diastereoselectivity via a nucleophile coordination-enabled SN 2'-allylation pathway.

Palladium-Catalyzed Alkylation of Phenol Derivatives

Palladium-Catalyzed Alkylation of Phenol Derivatives

Palladium-Catalyzed Cross-Coupling of Gem-Bromofluoroalkenes with Alkylboronic Acids for the Synthesis of Alkylated Monofluoroalkenes.

Monofluoroalkenes are versatile fluorinated synthons in organic synthesis, medicinal chemistry and materials science. In light of the importance of alkyl-substituted monofluoroalkenes efficient synthesis of these moieties still represents a synthetic challenge. Herein, we described a mild and efficient methodology to obtain monofluoroalkenes through a stereospecific palladium-catalyzed alkylation of gem-bromofluoroalkenes with primary and strained secondary alkylboronic acids under mild conditions. This novel strategy gives access to a wide range of functionalized tri- and tetrasubstituted monofluoroalkenes in high yield, with good functional group tolerance, independently from the gem-bromofluoroalkenes geometry.

Palladium-Catalyzed Alkylations Induced by Visible Light

Palladium-Catalyzed Alkylations Induced by Visible Light

Highly efficient synthesis and separation of fuel precursors from the concentrated ABE fermentation broth in a biphasic catalytic process

Developing a simple and efficient process for the conversion of biomass to petrol, diesel and jet fuels are our urgent mission due to the limitation of fossil fuels. Biobutanol is an important biomass-derived biofuel that can be converted to longer-chain petrol-range, diesel-range and jet-range fuels. Basing on the obtained concentrated acetone-1-butanol-ethanol (ABE) fermentation broth through a prefractionator, we report a palladium-catalysed alkylation of acetone with ethanol and 1-butanol to more efficiently produce C5–C11 fuel precursors in a reactor, where all the precursors and reactants were separated simultaneously by the salting-out effect of K3PO4. The precursors include ketones and a small amount of alcohols that can be reduced to alkanes for use as liquid transportation fuels. Tuning the reaction conditions can obtain different proportions of C5–C7 products (monoalkylation) and C9–C11 products (double alkylation) and the overall product contents accounted for up to 82 wt%. More than 99.5% of water from the concentrated ABE fermentation broth was removed by the salting-out effect of K3PO4.

Mechanism of Palladium-Catalyzed Alkylation of Aryl Halides with Alkyl Halides through C–H Activation: A Computational Study

Pd-catalyzed C(sp3)–H activation/alkylation of 2-tert-butylaryl halides with alkyl halides and CH2Br2 represents an advantageous strategy for the C–H functionalization with halogens as traceless directing groups. Several possible mechanisms were proposed for the reactions, but no further evidence was available to judge their relative feasibilities. Herein, a mechanistic study was performed with the aid of density functional theory (DFT) methods. Calculations indicate that the coupling of aryl bromides with alkyl chlorides is likely to generate alkylated benzocyclobutenes via aryl–Br oxidative addition on Pd(0) catalysts, C(sp3)–H activation, alkyl–Cl oxidative addition, aryl–alkyl reductive elimination, aryl–H activation, and aryl–C(sp3) reductive elimination. The coupling of aryl iodides with CH2Br2 is likely to generate indane derivatives via aryl–I oxidative addition, C(sp3)–H activation, alkyl–Br oxidative addition, aryl–CH2Br reductive elimination, alkyl–Br oxidative addition, C(sp3)–alkyl reductive ...

Intramolecular Construction of Trifluoromethyl Group by the Palladium-Catalyzed Alkylation of 2,3,3-Trifluoroallylic Carbonates with Indoles.

The palladium-catalyzed alkylation reaction of 2,3,3-trifluoroallylic carbonates with indoles afforded a trifluoromethyl group possessing 3-substituted indole derivatives. The reaction proceeded via attack of the C-3 carbon of the indoles onto the C-2 position of the allylic moiety and intramolecular construction of the trifluoromethyl group by the intramolecular fluorine atom shift from the C-2 position to the C-3 position of the allyl unit.

ChemInform Abstract: Palladium‐Catalyzed Domino Heck/Intermolecular C—H Bond Functionalization: Efficient Synthesis of Alkylated Polyfluoroarene Derivatives.

An efficient palladium-catalyzed alkylation of electron-deficient polyfluoroarenes is described. The protocol provides a useful and operationally simple access to a broad scope of alkylated polyfluoroarene derivatives in moderate to excellent yields. This also represents the first example of the introduction of a polyfluoroarene structure involving an alkylpalladium(II) intermediate.

Palladium-Catalyzed Domino Heck/Intermolecular C-H Bond Functionalization: Efficient Synthesis of Alkylated Polyfluoroarene Derivatives.

An efficient palladium-catalyzed alkylation of electron-deficient polyfluoroarenes is described. The protocol provides a useful and operationally simple access to a broad scope of alkylated polyfluoroarene derivatives in moderate to excellent yields. This also represents the first example of the introduction of a polyfluoroarene structure involving an alkylpalladium(II) intermediate.

Fei-Phos ligand-controlled asymmetric palladium-catalyzed allylic substitutions with structurally diverse nucleophiles: scope and limitations

The asymmetric palladium-catalysed alkylation of structurally diverse nucleophiles, including alcohols, activated methylene compounds, indoles, and aromatic amines, led to the formation of corresponding products in good yields and high enantioselectivities (up to 99% ee).

Synthesis of chiral α-hydroxy acids via palladium-catalyzed C(sp(3))-H alkylation of lactic acid.

Herein we report a Pd-catalyzed alkylation of lactic acid with the assistance of 8-aminoquinoline auxiliary. A wide range of alkyl iodides bearing β-hydrogen atoms are compatible with the reaction conditions, providing a practical and straightforward alternative to access chiral α-hydroxy acids (AHAs). The new reactions have been applied for the synthesis of isotope-labeled AHAs and a sugar-containing complex AHA.

Palladium-catalyzed alkylation of unactivated C(sp3)–H bonds with primary alkyl iodides at room temperature: facile synthesis of β-alkyl α-amino acids

Practical synthesis of β-alkyl α-amino acidsviaC(sp3)–H alkylation at room temperature.

ChemInform Abstract: Pd(II)‐Catalyzed Alkylation of Unactivated C(sp3)—H Bonds: Efficient Synthesis of Optically Active Unnatural α‐Amino Acids.

A palladium-catalyzed alkylation of primary and secondary C(sp3)–H bonds with alkyl iodides and/or bromides for the synthesis of optically active unnatural α-amino acids (α-AAs) is described. This process is scalable and tolerates a variety of functional groups with complete retention of chirality, providing an efficient new strategy for the synthesis of various unnatural α-amino acid derivatives.

Stereoselective Synthesis of β-Alkylated α-Amino Acids via Palladium-Catalyzed Alkylation of Unactivated Methylene C(sp3)–H Bonds with Primary Alkyl Halides

We report a new set of reactions based on the Pd-catalyzed alkylation of methylene C(sp(3))-H bonds of aliphatic quinolyl carboxamides with α-haloacetate and methyl iodide and applications in the stereoselective synthesis of various β-alkylated α-amino acids. These reactions represent the first generally applicable method for the catalytic alkylation of unconstrained and unactivated methylene C-H bonds with high synthetic relevance. When applied with simple isotope-enriched reagents, they also provide a convenient and powerful means to site-selectively incorporate isotopes into the carbon scaffolds of amino acid compounds.

Integration of chemical catalysis with extractive fermentation to produce fuels

Nearly one hundred years ago, the fermentative production of acetone by Clostridium acetobutylicum provided a crucial alternative source of this solvent for manufacture of the explosive cordite. Today there is a resurgence of interest in solventogenic Clostridium species to produce n-butanol and ethanol for use as renewable alternative transportation fuels. Acetone, a product of acetone-n-butanol-ethanol (ABE) fermentation, harbours a nucleophilic α-carbon, which is amenable to C-C bond formation with the electrophilic alcohols produced in ABE fermentation. This functionality can be used to form higher-molecular-mass hydrocarbons similar to those found in current jet and diesel fuels. Here we describe the integration of biological and chemocatalytic routes to convert ABE fermentation products efficiently into ketones by a palladium-catalysed alkylation. Tuning of the reaction conditions permits the production of either petrol or jet and diesel precursors. Glyceryl tributyrate was used for the in situ selective extraction of both acetone and alcohols to enable the simple integration of ABE fermentation and chemical catalysis, while reducing the energy demand of the overall process. This process provides a means to selectively produce petrol, jet and diesel blend stocks from lignocellulosic and cane sugars at yields near their theoretical maxima.

Palladium‐Catalyzed Alkylation of 1,4‐Dienes by CH Activation

Aktiviert: Die Titelreaktion verläuft mit einer hohen Bandbreite an Nucleophilen und 1,4-Dienen unter milden Bedingungen und bietet direkten Zugang zu 1,3-Dien-Produkten mit hoher Regio- und Stereokontrolle (siehe Schema; 2,6-DMBQ=2,6-Dimethylbenzochinon). Dies ist die erste katalytische allylische Alkylierung, die in Abwesenheit von Sulfoxidliganden stattfindet.

Palladium‐Catalyzed Allylic Alkylation of Carboxylic Acid Derivatives: N‐Acyloxazolinones as Ester Enolate Equivalents

A general asymmetric allylic alkylation of ester enolate equivalents at the carboxylic acid oxidation state is reported. N-Acylbenzoxazolinone-derived enol carbonates are synthesized in good yield and employed in the palladium-catalyzed alkylation reaction. Good yields (up to 99%) and enantioselectivities (up to 99% ee) are obtained and the imide products are readily converted to a series of carboxylic acid derivatives without loss of enantiopurity. High enantioselectivity in the reaction is achieved by a new strategy for ligand design involving variation of the steric properties of the diarylphosphine moiety.

Synthesis of new fluorous modular chiral ligand derivatives from amino alcohols and application in enantioselective carbon–carbon bond-forming alkylation reactions

N-Trifluoracyl β-chalcogeno amides and N-perfluoracyl β-thio amide ligands were prepared by a simple and efficient reaction sequence. These new ligands were evaluated in palladium-catalyzed alkylation of rac-( E)-1,3-diphenyl-2-propenyl acetate in the presence of dimethyl malonate and an enantioselectivity of up to 99% was obtained. After catalysis, the fluorous ligand can be easily recovered by liquid–liquid extraction and reused without loss in the activity.

β-Amino Alcohol Derived β-Hydroxy- and β-(o-Diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides: An Ester−Amide Ligand Structural Model for the Palladium-Catalyzed Allylic Alkylation Reaction

A commercially available collection of beta-amino alcohols have been converted to their corresponding beta-hydroxy- and beta-(o-diphenylphosphino)benzoyloxy(o-diphenylphosphino)benzamides 11a-f and 12a-f and have been employed in the Tsuji-Trost asymmetric alkylation reaction with 1,3-diphenylpropenyl acetate. With the exception of ligands 11b and 11f, the beta-hydroxybenzoyloxy(o-diphenylphosphino)benzamide ligands 11a-f primarily afforded the (R)-enantiomer of the product. In contrast, the bis(phosphine) ligands 12a-f consistently afforded the (S)-enantiomer. The best ligand (12c) was derived from cis-(1R,2S)-2-amino-1,2-diphenyl-1-ethanol, and when applied in the asymmetric allylic alkylation reaction, it yielded the product in an enantiomeric ratio of 97.8.22 favoring the (S)-enantiomer. A computational study was conducted on the conformation that this ligand might adopt in the palladium-catalyzed alkylation reaction as compared to that of the Trost ligand 1a.