One-Pot Synthesis Of Ketones Research Articles

TfOH-Catalyzed Facile Access for One-Pot Synthesis of β-Acylamino Ketones by Avoiding the Usage of Acetyl Chloride

AbstractWe have developed a TfOH-catalyzed, highly efficient protocol for the synthesis of biologically active β-acylamino ketones from aldehyde, ketone, and nitrile by avoiding the use of acetyl chloride. The reaction proceeds through a sequential aldol reaction followed by a nucleophilic attack of nitrile and hydrolysis of nitrile in one pot. The attractive features of this tandem process are mild reaction conditions, high atom economy, broad substrate scope with 51–87% yield, gram-scale reaction, and ease of operation.

One-pot three-component synthesis of α-methylated ketones from secondary and primary aryl alcohols

One-pot synthesis of α-methylated ketones from secondary and primary alcohols via a triple dehydrogenative method is presented.

Palladium-mediated CO2 extrusion followed by insertion of ketenes: translating mechanistic studies to develop a one-pot method for the synthesis of ketones

Multistage mass spectrometry (MSn) experiments were used to explore extrusion–insertion (ExIn) reactions of the palladium complex [(phen)Pd(O2CPh)]+ (phen, 1,10-phenanthroline). Under collision-induced dissociation (CID) conditions, the organopalladium cation [(phen)Pd(Ph)]+ was formed via decarboxylation and was found to react with phenylmethylketene to yield the enolate [(phen)Pd(CPhMeC(O)Ph)]+ via an insertion reaction. A further stage of CID revealed that the enolate fragments via loss of styrene to form the acyl complex [(phen)Pd(C(O)Ph)]+. Formation of both the coordinated enolate and acyl anions is supported by density functional theory (DFT) calculations. Attempts to develop a palladium-mediated one-pot synthesis of ketones from 2,6-dimethoxybenzoic acid as the key substrate and the ketene substrates R1R2C═C═O (R1 = Ph, R2 = Me; R1 = R2 = Ph) proved challenging owing to low yields and side product formation.

Catalytic reductive ring opening of epoxides enabled by zirconocene and photoredox catalysis

Catalytic reductive ring opening of epoxides enabled by zirconocene and photoredox catalysis

Recyclable palladium-catalyzed Suzuki coupling of aromatic triazine esters: A practical one-pot synthesis of aryl ketones from aromatic acids

An efficient heterogeneous palladium-catalyzed Suzuki coupling of aromatic triazine esters with arylboronic acids has been developed. The reaction proceeds smoothly in toluene at 110 °C using 2 mol% of MCM-41-bound bidentate phosphine palladium complex [MCM-41-2P-Pd(OAc)2] as catalyst and provides a novel and practical method for the synthesis of aryl ketones starting from readily available aromatic acids in a one-pot procedure with moderate to excellent yields. The MCM-41-2P-Pd(OAc)2 catalyst can be reused at least seven times without any apparent decrease in its catalytic activity.

Cobalt-Catalyzed Aerobic Oxidative Cleavage of Alkyl Aldehydes: Synthesis of Ketones, Esters, Amides, and α-Ketoamides.

A widely applicable approach was developed to synthesize ketones, esters, amides via the oxidative C-C bond cleavage of readily available alkyl aldehydes. Green and abundant molecular oxygen (O2 ) was used as the oxidant, and base metals (cobalt and copper) were used as the catalysts. This strategy can be extended to the one-pot synthesis of ketones from primary alcohols and α-ketoamides from aldehydes.

Facile one-pot synthesis of ketones from primary alcohols under mild conditions

One-pot transformation of primary alcohols to ketones was achieved by using dibromoisocyanuric acid and Fe2O3. This synthetic method provides a variety of ketones in high yield under mild reaction conditions.

Identification of an α-Oxoamine Synthase and a One-Pot Two-Step Enzymatic Synthesis of α-Amino Ketones.

Alb29, an α-oxoamine synthase involved in albogrisin biosynthesis in Streptomyces albogriseolus MGR072, was characterized and responsible for the incorporation of l-glutamate to acyl-coenzyme A substrates. Combined with Alb29 and Mgr36 (an acyl-coenzyme A ligase), a one-pot enzymatic system was established to synthesize seven α-amino ketones. When these α-amino ketones were fed into the alb29 knockout strain Δalb29, respectively, the albogrisin analogs with different side chains were observed.

Copper-Catalyzed Hydroalumination of Allenes with Diisobutylaluminum Hydride: Synthesis of Allylic Ketones with α-Quaternary Centers via Tandem Allylation/Oppenauer Oxidation.

An efficient and straightforward approach to allylaluminum reagent synthesis through Cu-catalyzed hydroalumination of readily accessible allenes with diisobutylaluminum hydride is described. The N-heterocyclic carbene-based copper complex promotes hydride addition to various functionalized allenes under mild reaction conditions. The catalytic reaction is applied to a highly selective one-pot synthesis of allylic ketones with α-tertiary and α-quaternary centers through tandem nucleophilic addition of in situ-generated allylaluminums to aldehydes/Oppenauer oxidation.

One-Pot Formal Dehydrogenative Ketone Synthesis from Aldehydes and Non-activated Hydrocarbons.

Ketones are a fundamental functionality found throughout a range of natural and synthetic compounds, making their synthesis essential throughout the chemical disciplines. Herein, we describe a one-pot synthesis of ketones via decatungstate-mediated formal dehydrogenative coupling between aldehydes and non-activated hydrocarbons. A variety of substituted benzaldehydes and cycloalkanes could be used in the optimized reaction to produce the desired ketones in moderate yields. The decatungstate photocatalyst functions in two reactions in this synthesis, catalyzing both the coupling and oxidation steps of the process. Notably, the reaction displays both high atom economy and sustainability, as it uses light and oxygen as key energy sources.

Ketone Synthesis from Benzyldiboronates and Esters: Leveraging α-Boryl Carbanions for Carbon-Carbon Bond Formation.

An alkoxide-promoted method for the synthesis of ketones from readily available esters and benzyldiboronates is described. The synthetic method is compatible with a host of sterically differentiated alkyl groups, alkenes, acidic protons α to carbonyl groups, tertiary amides, and aryl rings having common organic functional groups. With esters bearing α-stereocenters, high enantiomeric excess was maintained during ketone formation, establishing minimal competing racemization by deprotonation. Monitoring the reaction between benzyldiboronate and LiOtBu in THF at 23 °C allowed for the identification of products arising from deborylation to form an α-boryl carbanion, deprotonation, and alkoxide addition to form an "-ate" complex. Addition of 4-trifluoromethylbenzoate to this mixture established the α-boryl carbanion as the intermediate responsible for C-C bond formation and ultimately ketone synthesis. Elucidation of the role of this intermediate leveraged additional bond-forming chemistry and enabled the one-pot synthesis of ketones with α-halogen atoms and quaternary centers with four-different carbon substituents.

Further Studies on Ni/Zr-mediated One-pot Ketone Synthesis: Use of a Mixture of NiI- and NiII-catalysts Greatly Improves the Molar Ratio of Coupling Partners

Abstract A new Ni/Zr-mediated one-pot ketone synthesis is developed, with use of a mixture of (Me)3tpy·NiII- and py-(Me)imid·NiIICl2-catalysts. The NiI-catalyst selectively activates iodides, whereas the NiII-catalyst activates thio-pyridine esters. An adjustment of a relative loading of the two catalysts allows to tune the relative rate of the two activations and trap a short-lived radical intermediate(s) efficiently. Thus, the new method makes one-pot ketone synthesis highly effective even with a 1:1 mixture of the coupling partners. The synthetic value of the new method is demonstrated with the C-C bond formation at the final stage of a convergent halichondrin-synthesis.

One-Pot Synthesis of O-Heterocycles or Aryl Ketones Using an InCl3/Et3SiH System by Switching the Solvent.

An efficient one-pot synthesis of O-heterocycles or aryl ketones has been achieved using Et3SiH in the presence of InCl3 via a sequential ionic hydrogenation reaction by switching the solvent. This methodology can be used to construct C-O bonds and to prepare conjugate reduction products, including chromans, tetrahydrofurans, tetrahydropyrans, dihydroisobenzofurans, dihydrochalcones, and 1,4-diones in a facile manner. In addition, a novel plausible mechanism involving a conjugate reduction and a tandem reductive cyclization was verified by experimental investigations.

Enantioselective one-pot synthesis of β-sulfonyl ketones and trisubstituted tetrahydrothiophenes via β-elimination/cycloaddition sequence

A mild and efficient enantioselective one-pot synthesis of β-sulfonyl ketones and trisubstituted tetrahydrothiophenes via introducing 1,4-dithiane-2,5-diol to the simple kinetic resolution of β-sulfonyl ketones has been described herein. The one-pot reaction sequence including kinetic resolution and cascade sulfa-Michael/Aldol reaction proceeded successively to afford corresponding sulfonyl ketones and tetrahydrothiophenes with high enantioselectivities (85%–98% ee and 84%–95% ee).

One-pot synthesis of α-phenylsulfinyl ketones by reaction of phenyl benzenethiosulfinate with enolate anions, and synthesis of sulfoxides and sulfides by its reaction with Grignard reagents

Phenyl benzenethiosulfinate reacts with enolate anions derived from ketones to give α-phenylsulfinyl ketones directly, together with minor amounts of α-phenylsulfanyl ketones. These are easily separated by forming the water-soluble sodium salts of the sulfinyl compounds. Grignard reagents also react with phenyl benzenethiosulfinate, to give mixtures of sulfoxides and sulfides.

Zirconium/Nickel-Mediated One-Pot Ketone Synthesis.

A zirconium/nickel-mediated one-pot synthesis of ketones is reported. In the presence of Zn or Mn, Cp2 ZrCl2 was found to dramatically accelerate the coupling and suppress side product formation via an I→SPy displacement at the same time. Unlike Zn/Pd- and Fe/Cu-mediated one-pot ketone syntheses, the new method is effective for nucleophiles bearing OR or equivalent functional groups at the α-position. A mechanism comprising a nickel catalytic cycle, a zirconium catalytic cycle, and Zr→Ni transmetalation is proposed, and Cp2 ZrCl2 and/or low-valent Zr species are suggested to play crucial dual roles.

Unified, Efficient, and Scalable Synthesis of Halichondrins: Zirconium/Nickel-Mediated One-Pot Ketone Synthesis as the Final Coupling Reaction.

Unified, efficient, and scalable syntheses of the halichondrin natural products are reported. A newly developed Zr/Ni-mediated one-pot ketone synthesis was used to couple the two halves of the final product at a late stage in the synthesis. With the use of a slight excess of the left halves, the desired ketones were isolated in yields of 80-90 %. The halichondrins were obtained from these ketones in two steps, namely desilylation and [5,5]-spiroketal formation. The new synthetic route was effective for the total synthesis of all members in the homohalichondrin subgroup. The scalability of this process was demonstrated with halichondrin B; 150 mg of halichondrin B (68 % overall yield) were obtained from 200 mg of the right-half precursor.

NiFe2O4@SiO2–PPA Nanoparticle: A Green Nanocatalyst for the Synthesis of β-Acetamido Ketones

ABSTRACTIn this work, silica coated magnetic nanoparticles of modified polyphosphoric acid (NiFe2O4@SiO2–PPA deigned as NFS–PPA) represent as a reusable and green catalyst for one-pot four-component synthesis of β-acetamido ketones at room temperature under solvent-free conditions. This catalyst was synthesized and characterized by X-ray diffractions, transmission electron microscopy, scanning electron microscopy and vibrating sample magnetometry. The magnetic catalyst can be easily removed by a simple magnet and reused up to five times without any loss of its high catalytic activity. In addition to facility, this protocol enhances product purity and promises economic and also environmental profits.

Fe/Cu-Mediated One-Pot Ketone Synthesis.

An Fe/Cu-mediated one-pot ketone synthesis was reported. Unlike Ni- and Pd-mediated one-pot ketone syntheses, the reported Fe/Cu-mediated method allowed selective activation and coupling of alkyl iodides over vinyl iodides. The newly developed one-pot ketone synthesis was applied to a synthesis of vinyl iodide/ketone 13, the left half of halichondrin B, as well as vinyl iodide/ketone 8a, the C20-C26 building block of halichondrins.

Nano-Rb2HPW12O40 as an Efficient and Novel Catalyst for One-Pot Synthesis of β-Amino Ketones.

The aim of the research described was to study Rb2HPW12O40 as a green and heterogeneous catalyst for the Mannich reaction. One-pot multi-component condensation of an aldehyde, an amine and a ketone at ambient temperature affords the corresponding β-amino ketones using novel nano-sized Rb2HPW12O40. Simple purification, short reaction time and high yield are some of the advantages of this reaction. Also, the catalyst can be readily isolated. The nano catalyst Rb2HPW12O40 has been characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscopy.