Catalytic Hydroalkylation Research Articles

KOtBu/DMF-Mediated Hydroalkylation of Alkenes via Benzylic C-H Bond Activation.

Catalytic hydroalkylation reaction of alkenes with benzylic hydrocarbons involving t-BuOK/DMF-mediated benzylic C-H bond activation is demonstrated. This direct and operational simple protocol affords a rapid and reliable access to a wide scope of benzylic compounds in good-to-excellent yields. The benzylic C-H's of either activated diarylmethanes (pKa ∼ 32.2) and benzyl thioethers (pKa ∼ 30.8) or inert alkylbenzenes could all act as useful synthetic platforms to be conveniently alkylated under mild reaction conditions.

Cooperative effect of multi-active sites in WOx-modified ZrO2 supported highly dispersed Pd catalysts for promoting benzene hydroalkylation

Designing efficient metal–acid bifunctional catalysts is a challenging task to achieve the one-step benzene hydroalkylation to produce cyclohexylbenzene (CHB), which has significant importance due to the economic potential for the industrial production of phenol. In this study, a series of WOx-modified ZrO2 supported highly dispersed Pd catalysts were developed by modulating the surface acidity of ZrO2 through the introduction of WOx species. The as-constructed Pd/WOx-ZrO2 catalyst bearing a low Pd loading of 0.4 wt% and a W content of 21 wt% exhibited a superior catalytic performance, along with an unprecedentedly high productivity of CHB (144.6 mmolCHB·gcat−1·h−1), much higher than those obtained by using the state-of-the-art catalysts. It was demonstrated that highly dispersed Pd species could promote the formation of active hydrogen species and favor the hydrogen spillover on the catalyst surface that induced the generation of surface oxygen vacancies and Brønsted acidic sites originating from surface-loaded WOx. Comprehensive structural characterizations and catalytic experiments showed that the favorable metal–acid cooperation on Pd/WOx-ZrO2 catalysts and the cooperation between Lewis acid sites and Brønsted acid sites, as well as the presence of abundant defective oxygen vacancies, efficiently regulated the adsorption and activation of molecular hydrogen, benzene, and cyclohexene intermediate, leading to the improved catalytic hydroalkylation activity. These findings provide new high-performance metal–acid bifunctional catalysts with multi-active site cooperation structures for one-step hydroalkylation of benzene to CHB.

Dearomatization of Unactivated Arenes via Catalytic Hydroalkylation

The dearomative cyclization of linear amides to complex spirocyclic butyrolactams has been enabled by photoredox catalysis through a reductive radical-polar crossover mechanism. This mechanism operates with precision on unactivated aromatic substrates to give a wide range of 1,4-hydroalkylation products. This method utilizes a simple organic catalyst/reductant pair to deliver products in a highly flexible manner with respect to substitution, and the products can be further functionalized under simple conditions to afford a collection of motifs. The mechanistic analysis performed here outlines the salient features of this strategy, which were applied to prepare a collection of complex scaffolds including the anticonvulsive agent gabapentin.

Enantio- and Diastereoselective Synthesis of Homoallylic α-Trifluoromethyl Amines by Catalytic Hydroalkylation of Dienes.

We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by the catalytic hydroalkylation of terminal dienes. Trifluoromethyl-substituted isatin-derived azadienolate nucleophiles undergo γ-selective alkylation with a Pd-DTBM-SEGPHOS catalyst, which additionally promotes regioselective addition to the diene and delivers products in up to 86% yield, 10:1 dr, and 97.5:2.5 er.

Catalytic Hydroalkylation of Allenes

AbstractWe have developed a catalytic method for the hydroalkylation of allenes using alkyl triflates as electrophiles and silane as a hydride source. The reaction has an excellent substrate scope and is compatible with a wide range of functional groups, including esters, aryl halides, aryl boronic esters, sulfonamides, alkyl tosylates, and alkyl bromides. We found evidence for a reaction mechanism that involves unusual dinuclear copper ally complexes as catalytic intermediates. The unusual structure of these complexes provides a rationale for their unexpected reactivity.

Catalytic Hydroalkylation of Allenes.

We have developed a catalytic method for the hydroalkylation of allenes using alkyl triflates as electrophiles and silane as a hydride source. The reaction has an excellent substrate scope and is compatible with a wide range of functional groups, including esters, aryl halides, aryl boronic esters, sulfonamides, alkyl tosylates, and alkyl bromides. We found evidence for a reaction mechanism that involves unusual dinuclear copper ally complexes as catalytic intermediates. The unusual structure of these complexes provides a rationale for their unexpected reactivity.

ChemInform Abstract: Diastereoselective Synthesis of Vicinal Tertiary and N‐Substituted Quaternary Stereogenic Centers by Catalytic Hydroalkylation of Dienes.

An efficient and diastereoselective (CDC)–Rh-catalyzed hydroalkylation of dienes with 1,3-oxazol-5(4H)-ones is reported. Aryl and alkyl substituted dienes are converted to α,α-substituted oxazolones (24 examples) by the formation of N-substituted quaternary carbon stereogenic centers in good yields (up to 96%) and with high diastereoselectivity (>20 : 1 dr). The reaction is tolerant of a range of dienes and oxazolones bearing various functional groups. Utility of the oxazolone products is illustrated through hydrolysis to form α,β-substituted α-amino acid analogues and stereoselective epoxidation of the resultant alkene to create four contiguous stereocenters.

Iridium-Catalyzed Intramolecular Methoxy C-H Addition to Carbon-Carbon Triple Bonds: Direct Synthesis of 3-Substituted Benzofurans from o-Methoxyphenylalkynes.

Catalytic hydroalkylation of an alkyne with methyl ether was accomplished. Intramolecular addition of the C-H bond of a methoxy group in 1-methoxy-2-(arylethynyl)benzenes across a carbon-carbon triple bond took place efficiently either in toluene at 110 °C or in p-xylene at 135 °C in the presence of an iridium catalyst. The initial 5-exo cyclization products underwent double-bond migration during the reaction to give 3-(arylmethyl)benzofurans in high yields.

Diastereoselective synthesis of vicinal tertiary and N-substituted quaternary stereogenic centers by catalytic hydroalkylation of dienes.

An efficient and diastereoselective (CDC)-Rh-catalyzed hydroalkylation of dienes with 1,3-oxazol-5(4H)-ones is reported. Aryl and alkyl substituted dienes are converted to α,α-substituted oxazolones (24 examples) by the formation of N-substituted quaternary carbon stereogenic centers in good yields (up to 96%) and with high diastereoselectivity (>20 : 1 dr). The reaction is tolerant of a range of dienes and oxazolones bearing various functional groups. Utility of the oxazolone products is illustrated through hydrolysis to form α,β-substituted α-amino acid analogues and stereoselective epoxidation of the resultant alkene to create four contiguous stereocenters.

Diastereoselective synthesis of vicinal tertiary and N-substituted quaternary stereogenic centers by catalytic hydroalkylation of dienes

Diastereoselective synthesis of vicinal tertiary and N-substituted quaternary stereogenic centers by catalytic hydroalkylation of dienes

Selective catalytic hydroalkylation and deoxygenation of substituted phenols to bicycloalkanes

Phenol and substituted phenols are hydroalkylated and hydrodeoxygenated to bi-cycloalkanes in a tandem reaction over Pd nanoclusters supported on a large-pore molecular sieve HBEA at 473–523K using water as solvent. The HBEA-supported Pd catalyst (metal–acid ratio: 1:22mol/mol) optimally balances the competing rates of metal catalyzed hydrogenation as well as of solid acid-catalyzed dehydration and carbon–carbon coupling to combine hydrodeoxygenation and dimerization of phenol derivatives to C12–C18 bicycloalkanes in a single reaction sequence. A detailed kinetic study of the elementary reactions of (substituted) phenol and their potential products (cyclohexanol, cyclohexanone, and cyclohexene) demonstrates that phenol selectively reacts with the in situ generated cyclohexanol or cyclohexene on Brønsted acid sites. The acid-catalyzed alkylation of phenol with alcohol intermediates and alcohol dehydration are parallel reactions, which are subtly influenced by the competing hydrogenation reactions as well as by the presence of water as solvent. IR spectroscopy of adsorbed species and preliminary molecular modeling indicate that phenol and cyclohexanol enrichment in the large pores of zeolite HBEA is critical for the high activity and hydroalkylation selectivity.

Catalytic Hydroalkylation of Olefins by Stabilized Carbon Nucleophiles Promoted by Dicationic Platinum(II) and Palladium(II) Complexes

The coordinated olefin in dicationic platinum(II) and palladium(II) complexes [M(PNP)(olefin)](SbF6)2 (M = Pt, Pd; PNP = 2,6-bis(diphenylphosphinomethyl)pyridine; olefin = ethylene, propylene) reacts with β-dicarbonyl compounds (pentane-2,4-dione and methyl-3-oxobutanoate). If the proton released after the nucleophilic attack is trapped by a base, stable σ-alkyl derivatives [(PNP)M-CH2-CH(R)CH(Ac)COR′]SbF6 (R = H, Me; R′ = Me, OMe) are formed; otherwise the M−C σ-bond can be cleaved by the proton, in the rate-determining step of a catalytic cycle that leads to the alkylated dicarbonyl compound. The β-diketone is intrinsically more reactive than the β-ketoester, but in the catalytic reaction of the former an inhibition effect is observed in the case of the platinum catalyst.

ChemInform Abstract: CATALYSTS FOR THE HYDROALKYLATION OF BENZENE, TOLUENE AND XYLENES

The catalytic hydroalkylation of benzene over palladium and fused salt (NaCl-AlCl3) was examined under hydrogen pressure. The combination catalyst of palladium and fused salt showed good activity for hydroalkylation, providing cyclohexylbenzene as the main product, with a small amount of bicyclohexyl. With 0.24% palladium supported on alumina, suitable reaction conditions were : a temperature of 120-140°, and a reaction time of 5-10 hr in the presence of fused salt (NaCl-AlCl3 ; molar ratio 1 : 1). Under these conditions, the yields of cyclohexylbenzene and bicyclohexyl were 54.7 and 5.1%, respectively. This catalyst system was applied to the hydroalkylation of toluene, xylenes and trimethylbenzenes. Based on the behavior of the fused salt, we suggest that NaAlCl4 represents an active species in the hydroalkylation reaction.

Catalysts for the hydroalkylation of benzene, toluene and xylenes.

The catalytic hydroalkylation of benzene over palladium and fused salt (NaCl-AlCl3) was examined under hydrogen pressure. The combination catalyst of palladium and fused salt showed good activity for hydroalkylation, providing cyclohexylbenzene as the main product, with a small amount of bicyclohexyl. With 0.24% palladium supported on alumina, suitable reaction conditions were : a temperature of 120-140°, and a reaction time of 5-10 hr in the presence of fused salt (NaCl-AlCl3 ; molar ratio 1 : 1). Under these conditions, the yields of cyclohexylbenzene and bicyclohexyl were 54.7 and 5.1%, respectively. This catalyst system was applied to the hydroalkylation of toluene, xylenes and trimethylbenzenes. Based on the behavior of the fused salt, we suggest that NaAlCl4 represents an active species in the hydroalkylation reaction.