Palladium-Catalyzed Hydroalkylation Research Articles

Palladium-Catalyzed Hydroalkylation of Alkoxyallenes Using Monofluorinated Nucleophiles

AbstractA branch-selective hydroalkylation of alkoxyallenes with monofluorinated nucleophiles was developed using palladium catalysis, allowing construction of valuable α-monofluoroalkylated allylic ethers. Notably, this represents the first catalytic hydrofluoroalkylation of alkoxyallenes. The practicability of this method is highlighted by its broad substrate scope and diversified product elaborations. Initial investigation of the asymmetric variant could afford chiral fluorine-containing allylic ethers with up to 68% ee.

Palladium-catalyzed hydroalkylation of methylenecyclopropanes with simple hydrazones.

A palladium-catalyzed hydroalkylation reaction of methylenecyclopropanes via highly selective C–C σ-bond scission was achieved under mild conditions, in which simple hydrazones served as carbanion equivalents. This method featured good functional group compatibility, affording high yields of C-alkylated terminal alkenes.

Palladium-Catalyzed Regioselective Hydroalkylation of 2-Fluoroallyl Acetates: Synthesis of Vinylmalonic Acid Ester Derivatives

The palladium-catalyzed hydroalkylation of 2-fluoroallyl acetates with the malonate anion and hydride was developed. The reaction proceeded through the C–F bond activation and provided vinylmalonic acid ester derivatives by the regioselective substitutions with the carbon nucleophile and hydride.

Palladium-Catalyzed Hydroalkylation of Allylic and Homoallylic Alcohol Derivatives

Palladium-Catalyzed Hydroalkylation of Allylic and Homoallylic Alcohol Derivatives

The palladium-catalyzed anti-Markovnikov hydroalkylation of allylic alcohol derivatives.

A palladium-catalyzed hydroalkylation reaction of protected allylic alcohols using alkylzinc bromide reagents is reported. This account includes numerous allylic, homoallylic, and bishomoallylic alcohol derivatives, all with a uniform selectivity of >20:1 for the anti-Markovnikov product. The reaction features the ability to deliver enantiomerically enriched alcohols in unfunctionalized regions, which results from the catalyst avoiding β-hydride elimination at the allylic position.

Anti-Markovnikov Hydroalkylation of Allylic Amine Derivatives via a Palladium-Catalyzed Reductive Cross-Coupling Reaction

Palladium-catalyzed hydroalkylation of allylic amine derivatives by alkylzinc reagents is reported. This reductive cross-coupling reaction yields anti-Markovnikov products using a variety of allylic amine protecting groups. Preliminary mechanistic studies suggest that a reversible β-hydride elimination/hydride insertion process furnishes the primary Pd-alkyl intermediate, which then undergoes transmetalation followed by reductive elimination to form a new sp(3)-sp(3) carbon-carbon bond.

Csp³-Csp³ Bond Formation via Palladium-Catalyzed Hydroalkylation of Styrenes

Csp^³-Csp^³ Bond Formation via Palladium-Catalyzed Hydroalkylation of Styrenes

Palladium-catalyzed hydroalkylation of styrenes with organozinc reagents to form carbon-carbon sp3-sp3 bonds under oxidative conditions.

An unconventional route for the formation of sp(3)-sp(3) C-C bonds from various styrenes and an organozinc reagent in a formal alkene hydroalkylation process is detailed. Mechanistically, this process is proposed to proceed by initial transmetalation followed by formation of a Pd-H species, which is subsequently trapped by the styrene.

Development, Scope, and Mechanism of the Palladium-Catalyzed Intramolecular Hydroalkylation of 3-Butenyl β-Diketones.

Reaction of 7-octene-2,4-dione (3) with a catalytic amount of PdCl2(CH3CN)2 (4) (10 mol %) in dioxane at room temperature for 16 h formed 2-acetylcyclohexanone (5) in 81% yield as a single regioisomer. Byproducts in the conversion of 3 to 5 include 2,4-octanedione (13), 2-acetyl-2-cyclohexenone (14), 2-acetylphenol (15), (E)- and (Z)-6-octene-2,4-dione (17), (E)- and (Z)-5-octene-2,4-dione (18), the η3-β-diketonate chloride dimer {[η3-CH3CH2CH2CHCOHCHAc]Pd(Cl)}2 (12), and the π(allyl)palladium chloride dimer {[η3-CH3CHCHCHC(O)CH2Ac]Pd(Cl)}2 (16). The palladium-catalyzed cyclization of 3-butenyl β-diketones tolerated substitution at the terminal acyl carbon atom, the enolic carbon atom, and the terminal olefinic carbon atom. Deuterium-labeling studies, in conjunction with kinetic and in situ NMR experiments, supported a mechanism for the palladium-catalyzed hydroalkylation of 3-butenyl β-diketones initiated by 6-endo-trig attack of the enol carbon atom on a palladium-complexed olefin to form a palladium cy...

Development, Scope, and Mechanism of the Palladium-Catalyzed Intramolecular Hydroalkylation of 3-Butenyl β-Diketones

Reaction of 7-octene-2,4-dione (3) with a catalytic amount of PdCl2(CH3CN)2 (4) (10 mol %) in dioxane at room temperature for 16 h formed 2-acetylcyclohexanone (5) in 81% yield as a single regioisomer. Byproducts in the conversion of 3 to 5 include 2,4-octanedione (13), 2-acetyl-2-cyclohexenone (14), 2-acetylphenol (15), (E)- and (Z)-6-octene-2,4-dione (17), (E)- and (Z)-5-octene-2,4-dione (18), the η3-β-diketonate chloride dimer {[η3-CH3CH2CH2CHCOHCHAc]Pd(Cl)}2 (12), and the π(allyl)palladium chloride dimer {[η3-CH3CHCHCHC(O)CH2Ac]Pd(Cl)}2 (16). The palladium-catalyzed cyclization of 3-butenyl β-diketones tolerated substitution at the terminal acyl carbon atom, the enolic carbon atom, and the terminal olefinic carbon atom. Deuterium-labeling studies, in conjunction with kinetic and in situ NMR experiments, supported a mechanism for the palladium-catalyzed hydroalkylation of 3-butenyl β-diketones initiated by 6-endo-trig attack of the enol carbon atom on a palladium-complexed olefin to form a palladium cy...

Palladium‐Catalyzed Intramolecular Hydroalkylation of Alkenyl‐ β‐Keto Esters, α‐Aryl Ketones, and Alkyl Ketones in the Presence of Me3SiCl or HCl

Reaction of 3-butenyl beta-keto esters or 3-butenyl alpha-aryl ketones with a catalytic amount of [PdCl2(CH3CN)2] (2) and a stoichiometric amount of Me3SiCl or Me3SiCl/CuCl2 in dioxane at 25-70 degrees C formed 2-substituted cyclohexanones in good yield with high regioselectivity. This protocol tolerated a number of ester and aryl groups and tolerated substitution at the allylic, enolic, and cis and trans terminal olefinic positions. In situ NMR experiments indicated that the chlorosilane was not directly involved in palladium-catalyzed hydroalkylation, but rather served as a source of HCl, which presumably catalyzes enolization of the ketone. Identification of HCl as the active promoter of palladium-catalyzed hydroalkylation led to the development of an effective protocol for the hydroalkylation of alkyl 3-butenyl ketones that employed sub-stoichiometric amounts of 2, HCl, and CuCl2 in a sealed tube at 70 degrees C.

Palladium-catalyzed alkylation of unactivated olefins

Abstract The reaction of a 3-butenyl β-diketone with a catalytic amount of PdCl2(CH3CN)2 in dioxane at room temperature led to olefin hydroalkylation and formation of the corresponding 2-acylcyclohexanone in good yield as a single regioisomer. Deuterium-labeling experiments for the hydroalkylation of 7-octene-2,4-dione were in accord with a mechanism involving outer-sphere attack of the pendant enol on a palladium-complexed olefin to form a palladium cyclohexyl species, followed by palladium migration via iterative β-hydride elimination/addition and protonolysis from a palladium enolate complex. In comparison to a 3-butenyl β-diketone, reaction of a 4-pentenyl β-diketone with a catalytic amount of PdCl2(CH3CN)2 in the presence of CuCl2 led to oxidative alkylation and formation of the corresponding 2-acyl-3-methyl-2-cyclohexenone in good yield as a single isomer. Unactivated olefins tethered to less reactive carbon nucleophiles such as β-keto esters, α-aryl ketones, and even dialkyl ketones underwent palladium-catalyzed hydroalkylation in the presence of Me3SiCl or HCl to form the corresponding cyclohexanones in moderate-to-good yield with high regioselectivity.