Reductive α-alkylation of ketones with aldehydes at atmospheric pressure of carbon monoxide: the effect of fluoride activation in ruthenium catalysis

Fluoride additive to [(p-cymene)RuCl₂]₂, a readily available ruthenium catalyst, allows one to achieve milder conditions for the reductive alkylation of aldehydes with ketones using carbon monoxide as a reducing agent. The procedure is suitable for the broad substrate scope, and a probable explanation for the fluoride role was provided.     

Dinitrogen Activation and Addition to Unsaturated C−E (E=C,N, O,S) Bonds Mediated by Transition Metal Complexes

Dinitrogen (N₂) activation and functionalization is of fundamental interest and practical importance. This review focuses on N₂ activation and addition to unsaturated substrates, including carbon monoxide, carbon dioxide, heteroallenes, aldehydes, ketones, acid halides, nitriles, alkynes, and allenes, mediated by transition metal complexes, which afforded a variety of N−C bond formation products. Emphases are placed on the reaction modes and mechanisms. We hope that this work would stimulate further explorations in this challenging field.     

New synthesis of multisubstituted cyanocyclopropanes by the intramolecular SN2 alkylation and 1,3-CC insertion reaction of magnesium carbenoids as the key reactions

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides derived from ketones and aldehydes with lithium α-cyano carbanions gave nitrile adducts in high to quantitative yields. Treatment of the nitrile adducts derived from acetonitrile with excess i-PrMgCl in THF resulted in the formation of cyanocyclopropanes via the intramolecular S_N2 alkylation of the generated magnesium carbenoids. The intermediate of this reaction was proved to be a cyclopropylmagnesium chloride and was reactive with electrophiles to give multisubstituted cyanocyclopropanes. On the other hand, the reaction of the nitrile adducts derived from arylacetonitriles with i-PrMgCl resulted in the formation of 2-arylcyanocyclopropanes by the 1,3-carbon–carbon (1,3-CC) insertion reaction of the generated magnesium carbenoid intermediates. This reaction was found to proceed in a highly stereospecific manner. The key reactions, intramolecular S_N2 alkylation and 1,3-CC insertion reaction of the magnesium carbenoids, are the first examples for the reaction of the magnesium carbenoids bearing a nitrile functional group.     

Generation of alkyl hypochlorites in oxidation of alcohols with carbon tetrachloride catalyzed by vanadium and manganese compounds

Primary alcohols and diols with various structures were subjected to transformations into esters, aldehydes, ketones, and lactones under the action of carbon tetrachloride in the presence of manganese compounds (MnCl₂, MnO₂, Mn(OAc)₂, Mn(acac)₃) and vanadium compounds (VCl₅, V₂O₅, VO(acac)₂) as catalysts. These transformation proceeded with the involvement of alkyl hypochlorites, which were generated in the course of oxidation of alcohols with carbon tetrachloride catalyzed by manganese or vanadium compounds. The optimum molar ratios between the catalyst and reagents were determined, and the reaction conditions for the highly selective synthesis of esters, aldehydes, ketones, and lactones from alcohols were found.     

Copper‐Catalyzed Dehydrogenative Cross‐Coupling Reaction between Allylic CH Bonds and α‐CH Bonds of Ketones or Aldehydes

A dehydrogenative cross‐coupling reaction between allylic C?H bonds and the α‐C?H bond of ketones or aldehydes was developed using Cu(OTf)₂ as a catalyst and DDQ as an oxidant. This synthetic approach to γ,δ‐unsaturated ketones and aldehydes has the advantages of broad scope for both ketones and aldehydes as reactants, mild reaction conditions, good yields and atom economy. A plausible mechanism using Cu(OTf)₂ as a Lewis acid catalyst was also proposed (DDQ=2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone; Tf=trifluoromethanesulfonate).     

Ruthenium catalyzed β-selective alkylation of vinylpyridines with aldehydes/ketones via N2H4 mediated deoxygenative couplings

Umpolung (polarity reversal) tactics of aldehydes/ketones have greatly broadened carbonyl chemistry by enabling transformations with electrophilic reagents and deoxygenative functionalizations. Herein, we report the first ruthenium-catalyzed β-selective alkylation of vinylpyridines with both naturally abundant aromatic and aliphatic aldehyde/ketones via N₂H₄ mediated deoxygenative couplings. Compared with one-electron umpolung of carbonyls to alcohols, this two-electron umpolung strategy realized reductive deoxygenation targets, which were not only applicable to the regioselective alkylation of a broad range of 2/4-alkene substituted pyridines, but also amenable to challenging 3-vinyl and steric-embedded internal pyridines as well as their analogous heterocyclic structures.

Ruthenium-catalyzed β-selective alkylation of vinylpyridines with carbonyls (both aromatic and aliphatic ketones/aldehydes) via N₂H₄ mediated deoxygenative couplings was achieved.     

Complex bases. XIV. Use of sodamide containing complex bases as versatile,inexpensive reagents to generate carbanions

It is shown that Complex Bases NaNH₂-RONa are very efficient in carbanion preparations and allow alkylation of imines, aldehydes, 1,3-dithianes, dithioketals as well as methylsulfenylation of ketones.     

Réactivité des liaisons σ uranium-carbone: réactions du méthyltris(hexaméthyldisilylamido)uranium

The uranium-carbon σ bond of the methyltris(hexamethyldisilylamido)uranium, [(SiMe₃)₂N]₃UCH₃, was poorly reactive towards carbon monoxide insertion, but reacted readily with isocyanides, aliphatic nitriles and carbonyl compounds (aldehydes and ketones).“Acidic” hydrogens reacted under mild conditions; secondary amines gave the tetraamido compounds [(SiMe₃)₂N]₃UNR₂ and metallic hydrides gave the binuclear compounds with an isocarbonyl linkage.     

Four-Component Borocarbonylation of Vinylarenes Enabled by Cooperative Cu/Pd Catalysis: Access to β-Boryl Ketones and β-Boryl Vinyl Esters

We report here a general four-component synthetic procedure for the preparation of β-boryl ketones and β-boryl vinyl esters. Joint catalyzed by palladium and copper catalysts, borocarbonylative reaction between vinylarenes, aryl halides/triflates, B₂Pin₂, and carbon monoxide proceed successfully. A variety of synthetically useful β-boryl ketones were synthesized in good to high yields by using aryl iodides as the substrates. It is noteworthy that when aryl triflates were applied as the starting materials, β-boryl vinyl esters were synthesized in a similar manner and with broad functional group tolerance. A rational mechanism for this reaction was also proposed.     

Four‐Component Borocarbonylation of Vinylarenes Enabled by Cooperative Cu/Pd Catalysis: Access to β‐Boryl Ketones and β‐Boryl Vinyl Esters

We report here a general four‐component synthetic procedure for the preparation of β‐boryl ketones and β‐boryl vinyl esters. Joint catalyzed by palladium and copper catalysts, borocarbonylative reaction between vinylarenes, aryl halides/triflates, B₂Pin₂, and carbon monoxide proceed successfully. A variety of synthetically useful β‐boryl ketones were synthesized in good to high yields by using aryl iodides as the substrates. It is noteworthy that when aryl triflates were applied as the starting materials, β‐boryl vinyl esters were synthesized in a similar manner and with broad functional group tolerance. A rational mechanism for this reaction was also proposed.     

Enone Synthesis via Palladium Catalyzed Reductive Carbonylation of Terminal Acetylenes

Aryl vinyl ketones are prepared by the reaction of aryl iodides and terminal acetylenes in the presence of a catalytic amount of PdCl₂(PPh₃)₂, Cp₂TiCl₂ and a stoichiometric amount of Zn-Cu under an atmospheric pressure of carbon monoxide.     

Iron‐Catalyzed α‐Alkylation of Ketones with Alcohols

A general and benign iron‐catalyzed α‐alkylation reaction of ketones with primary alcohols has been developed. The key to success of the reaction is the use of a Knölker‐type complex as catalyst (2 mol %) in the presence of Cs₂CO₃ as base (10 mol %) under hydrogen‐borrowing conditions. Using 2‐aminobenzyl alcohol as alkylation reagent allows for the “green” synthesis of quinoline derivatives.     

A ruthenium-catalyzed one-pot method for α-alkylation of ketones with aldehydes

Ketones react with an array of aldehydes in dioxane at 80 °C in the presence of a catalytic amount of RuCl₂(PPh₃)₃ along with KOH to give the corresponding α-alkylated ketones in moderate to good yields. A reaction pathway involving base-catalyzed cross-aldol reaction between ketones and aldehydes to form α,β-unsaturated ketones and regioselective reduction of carbon-carbon double bond of α,β-unsaturated ketones is proposed for this catalytic process.     

Piano‐stool Ru (II) arene complexes that contain ethylenediamine and application in alpha‐alkylation reaction of ketones with alcohols

A series of piano‐stool Ru (II) complexes ( Ru _1–7 ) bearing ethylenediamine with aryl and aliphatic groups were prepared and fully characterized by ¹H, ¹³C, ¹⁹F and ³¹P NMR spectroscopy, FT‐IR and elemental analysis. The crystal structures of Ru _2–4 and Ru ₇ were determined by X‐ray crystallography. They were successfully applied to the alpha(α)‐alkylation of aliphatic and aromatic ketones with alcohols via the borrowing hydrogen strategy in mild reaction conditions within a short time. The catalytic system has a broad substrate scope, which allows the synthesis of alpha alkylated ketones with excellent yields. The electronic and steric effects of complexes on catalytic activity were analysed. The influence of the carbon chain length of the ligand on the alpha‐alkylation reaction of ketones was also investigated. The catalytic cycle was also examined by ¹H‐NMR spectroscopy in d₈‐toluene.     

Efficient synthesis of β-acetamido ketones using BF3/Et2O: a fertile approach toward avoiding usage of acetyl chloride

Abstract

A simple and efficient one pot synthesis of β-acetamido ketones from reaction of aldehydes, enolizable ketones, alkyl/aryl nitriles, and BF₃/Et₂O catalyst under microwave irradiations is described. This method allows synthesis of β-acetamido ketones without using corrosive and hazardous acetyl chloride. It is applicable for diversified aldehydes and active methylene ketones supported by synthesizing varieties of β-acetamido ketones. As per literature, majority of synthetic methods of β-acetamido ketones are restricted to use of acetonitrile lonely, as a nitrile component. This method is found to be equally effective for range of nitriles, also. Key features of reported method are simple reaction protocol, better yields, shorter reaction time, and nonhazardous reaction conditions which support the “Green Chemistry approach.”     

Carbonylative cross-coupling reaction of aryl iodides with alkylaluminums by palladium complex catalysis

Secondary and/or tertiary alcohols and unsymmetrical ketones have been obtained in moderate to good yields by the palladium-catalyzed (5 mol%) carbonylative coupling of aryl iodides with alkylaluminum compounds under very mild conditions (20–50°C, 1 atm of carbon monoxide). The type of the reaction product depended on the aluminum reagent employed. While the selective formation of secondary alcohols was observed in the reaction with i-Bu₃Al, the use of Et₃Al led to a mixture of a ketone and two alcoholic products. With Et₂AlCl predominantly unsymmetrical ketones were produced. In all cases, formation of directly cross-coupled products was not observed. DME and benzene can be used as solvents, but THF is unsuitable. Nickel catalysts were found to be ineffective for this reaction.     

Reactive organoallyl species generated from aryl halides and allene: allylation of α,β-unsaturated aldehydes and cyclic ketones employing Pd/In transmetallation processes

Allylation of α,β-unsaturated aldehydes and cyclic ketones promoted by Pd/In transmetallation processes has been studied. The unsaturated aldehydes underwent regioselective 1,2-addition to afford secondary homoally alcohols. The reactions have been performed using Pd(OAc)₂/PPh₃ as catalytic system and metallic indium affording the products in good yields. The same transformation with unsaturated ketones proved to be less efficient, while saturated cyclic ketones delivered generally excellent yields in the presence of CuI. In these latter processes the presence of a distal heteroatom influences the reaction rate.     

General Reductive Amination of Aldehydes and Ketones with Amines and Nitroaromatics under H2 by Recyclable Iridium Catalysts

Heterogeneous iridium catalysts were prepared and applied for the reductive amination of aldehydes and ketones with nitroaromatics and amines using H₂ . The iridium catalysts were prepared by pyrolysis of ionic liquid 1‐methyl‐3‐cyanomethylimidazoulium chloride ([MCNI ]Cl) with iridium chloride (IrCl₃ ) in activated carbons. Iridium particles were well dispersed and stable in the N‐doped carbon materials from [MCNI ]Cl with activated carbon. The Ir@NC (600‐2h) catalyst was found to be highly active and selective for the reductive amination of aldehydes and ketones using H₂ and a variety of nitrobenzenes and amines were selectively converted into the corresponding secondary and tertiary amines. The Ir@NC (600‐2h) catalyst can be reusable several times without evident deactivation.     

Synthesis of Early‐Transition‐Metal Carbide and Nitride Nanoparticles through the Urea Route and Their Use as Alkylation Catalysts

The use of urea as either a carbon or a nitrogen source enabled the synthesis of various early‐transition‐metal nitride and carbide nanoparticles (TiN, NbN, Mo₂N, W₂N, NbC_xN_1?x, Mo₂C and WC). The ability of these particles to promote alkylation reactions with alcohols was tested on benzyl alcohol and acetophenone at 150 °C for 20 h in xylene. Group IV and V ceramics proved to be able to catalyse the formation of 1,3‐diphenyl propenone, whereas group VI ceramics showed a tendency to promote the Friedel–Crafts‐type reaction of benzyl alcohol on xylene (the solvent). TiN featured the highest activity for the alkylation of ketones and was further tested for more difficult alkylations. Group VI ceramics were further investigated as catalysts for the Friedel–Crafts‐type alkylation of aromatics with activated alcohols. Interestingly, even hexanol could be effectively used for these reactions.     

Synthesis of Intermediates by Rhodium-Catalyzed Hydroformylation

The reaction of olefins with carbon monoxide and hydrogen to give aldehydes is referred to as hydroformylation (oxo reaction). As catalyst for this reaction rhodium is about three to four orders of magnitude more active than the more commonly employed cobalt. With special rhodium compounds, e.g. di-ν-chlorobis(ν-1,5-cyclooctadiene)dirhodium [RhCl(C₈H₁₂)]₂, in the presence of chiral phosphanes, even asymmetric hydroformylations can be achieved; however, the enantiomeric purity of the products (20–30%) is not high enough for industrial-scale syntheses.