Synthesis of functionalized dialkyl ketones from carboxylic acid derivatives and alkyl halides

Unsymmetrical dialkyl ketones can be directly prepared by the nickel-catalyzed reductive coupling of carboxylic acid chlorides or (2-pyridyl)thioesters with alkyl iodides or benzylic chlorides. A wide variety of functional groups are tolerated by this process, including common nitrogen protecting groups and C-B bonds. Even hindered ketones flanked by tertiary and secondary centers can be formed. The mechanism is proposed to involve the reaction of a (L)Ni(alkyl)(2) intermediate with the carboxylic acid derivative.     

Direct synthesis of p-nitrobenzoic acid and benzoic acids from benzyl ketones and acetophenones using the CAN/HOAc system

The synthesis of p-nitrobenzoic acid and benzoic acids from benzyl and methyl ketones has been described using cerium(IV) ammonium nitrate in acetic acid. This simple method for the oxidation of benzylic ketones can be used as a practical method for the synthesis of 4-nitrobenzoic acid.     

A novel pyrrolidine imide catalyzed direct formation of alpha,beta-unsaturated ketones from unmodified ketones and aldehydes

A method for direct, stereoselective preparation of (E)-alpha,beta-unsaturated ketones from ketones and aldehydes, promoted by a novel pyrrolidine imide organocatalyst, has been developed in moderate to high yields. Unlike the Claisen-Schmidt condensation and Lewis acid catalyzed tandem aldol-dehydration processes, this method provides mild reaction conditions to access alpha,beta-unsaturated ketones from simple, unmodified ketones. [reaction: see text]     

Dipyrryl ketones from dipyrrylmethanes

Dipyrrylmethanes are smoothly and efficiently oxidized to dipyrryl ketones by ceric ammonium nitrate in water-tetrahydrofuran-acetic acid solvent at room temperature.     

O,O-Diethyl dithiophosphoric acid mediated direct synthesis of thioamides from aldehydes and ketones

A general and convenient method for a one-pot conversion of aldehydes and ketones into thioamides has been developed. The protocol involves oximation of aldehydes and ketones followed by deoxygenative thioamidation of oximes with O,O-diethyl dithiophosphoric acid which acts as an acid as well a source of sulfur. The method is operationally simple, high yielding, and also applicable to the conversion of amides and nitriles into the corresponding thioamides.     

Synthesis of pyrroles from alkyl trans-2-methyoxycyclopropyl ketones

2-Alkylpyrroles were obtained by the reaction of alkyl trans-2-methoxycyclopropyl ketones with ammonium hydroxide. N-Substituted 2-alkylpyrroles were synthesized by the reaction of the indicated ketones with methylamine or aniline in acetic acid or methanol-acetic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1335–1336, October, 1990.     

On the facile dehydrohalogenation of amino acid derived chloromethyl ketones.

Amino acid derived chloromethyl ketones are shown to undergo a general dehydrohalogenation reaction under mild, basic, nonnucleophilic conditions to afford α-β-unsaturated ketones.     

CuBr2 mediated synthesis of 2-Aminothiazoles from dithiocarbamic acid salts and ketones

Abstract

In a one-pot procedure, CuBr₂ has been used as a efficient desulfurizing agent in the synthesis of 2-aminothiazoles by the condensation of in situ-generated 1-substituted thioureas from their dithiocarbamic acid salts, with in situ-generated α-bromoketones from ketones. All reactions were carried out under optimized reaction conditions and gave the target products in 61–95% yield.     

α-Hydroxylation of ketones using o-iodosylbenzoic acid

-o-Iodosylbenzoic acid (KOH/CH₃OH) converts various ketones to α-hydroxydimethyl-acetals in high yield with the advantageous feature of solubility of the reduction product o-iodobenzoic acid under the basic reaction conditions thus allowing isolation of the oxidation product by simple CH₂Cl₂ extraction.     

3-Pyrrolidinecarboxylic acid for direct catalytic asymmetric anti-Mannich-type reactions of unmodified ketones

We report the development of direct catalytic, enantioselective, anti-selective Mannich-type reactions between unmodified ketones and alpha-imino esters under mild conditions. The reactions were performed using 5-10 mol % of (R)-3-pyrrolidinecarboxylic or (R)-beta-proline as catalyst in an environmentally benign solvent, 2-PrOH, at room temperature. The anti-Mannich products were obtained in good yields with high diastereo- and enantioselectivities (up to anti/syn >99:1, 99% ee). While (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid is an excellent catalyst for the anti-Mannich-type reactions of aldehydes, it did not efficiently catalyze the corresponding Mannich-type reactions of ketones; (R)-3-pyrrolidinecarboxylic acid did efficiently catalyze the Mannich-type reactions of ketones. (S)-Proline or (S)-2-pyrrolidinecarboxylic acid has been reported to catalyze the Mannich-type reactions of ketones to afford the syn-products. Thus, the position of the carboxylic acid group on the pyrrolidine ring directs the stereoselection of the catalyzed reaction, providing either syn- or anti-Mannich products.     

1,3-diketones from acid chlorides and ketones: a rapid and general one-pot synthesis of pyrazoles

[reaction: see text] 1,3-Diketones were synthesized directly from ketones and acid chlorides and were then converted in situ into pyrazoles by the addition of hydrazine. This method is extremely fast, general, and chemoselective, allowing for the synthesis of previously inaccessible pyrazoles and synthetically demanding pyrazole-containing fused rings.     

An effective one-pot conversion of acid chlorides to aldehydes and ketones

Aldehydes and ketones were synthesized from their respective acid chlorides via a one-pot protocol. Morpholine amide intermediates that were readily prepared by the aminolysis of various acid chlorides with diisobutyl(morpholino)aluminum smoothly reacted with the reducing agent LDBMA and the organolithium reagents under mild reaction conditions (0 °C), giving almost excellent product yields of up to 95%.     

Synthesis of isoprenoid acids from isoprenoid ketones by the action of the diethyl ester of carbetboxymethylphosphonic acid

Summary A method for the synthesis of isoprenoid acids is proposed, based on the reaction of isoprenoid ketones with the diethyl ester of carbethoxymethylphosphonic acid.     

Catalytic asymmetric cyanosilylation of ketones by a chiral amino acid salt

In this Communication, we describe the first highly enantioselective cyanosilylation of ketones catalyzed by simple chiral amino acid salt. A broad range of aromatic, alpha,beta-unsaturated, heterocyclic ketones catalyzed by l-phenylglycine sodium salt gave the corresponding trimethylsilyl ethers of cyanohydrins in 75-96% yields with 86-97% enantioselectivities. A catalytic cycle based on experimental phenomena and studies has been proposed to explain the origin of this activation. The reaction employed commercially available and fully recyclable catalysts and involves a simple experimental procedure.     

Addition of grignard reagents to aryl acid chlorides: an efficient synthesis of aryl ketones

[chemical reaction: see text]. Direct addition of Grignard reagents to acid chlorides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether proceeds selectively to provide aryl ketones in high yields. A possible tridentate interaction between Grignard reagents and bis[2-(N,N-dimethylamino)ethyl] ether moderates the reactivity of Grignard reagents, preventing the newly formed ketones from nucleophilic addition by Grignard reagents.     

A new regiospecific synthesis of aryl ketones from palladocycles

Aromatic palladocycles undergo facile reaction with acid halides to reglospecifically provide aryl ketones In high yield.     

Preparation of aryl ketones via Ni-catalyzed Negishi-coupling reactions with acid chlorides

A Ni-catalyst-catalyzed cross-coupling reaction of organozinc reagents with acid chlorides has been successfully developed. Mild reaction conditions were required to complete the coupling reactions affording the corresponding aryl ketones in good to excellent yields.     

Electrochemical synthesis of ketones from acid chlorides and alkyl and aryl halides catalysed by nickel complexes

The nickel-catalysed electrochemical cross-coupling of acid chlorides and alkyl or aryl halides in acetonitrile affords unsymmetric ketones in good to high yields. The reaction can be performed under very simple and mild conditions in a diaphragmless cell. A zinc rod as the sacrificial anode has been found to be the most efficient.     

Calcium-promoted Pictet-Spengler reactions of ketones and aldehydes

Calcium bis-1,1,1,3,3,3-hexafluoroisopropoxide is shown to be an effective catalyst for Pictet-Spengler reactions of 3-hydroxyphenethylamine and 3-hydroxy-4-methoxyphenethylamine with various aldehydes and ketones. Previous Lewis acid catalyzed Pictet-Spengler reactions of unactivated ketones typically require two separate reactions (imine formation, cyclization) to obtain the same results. The reactions described within directly provide 1,1'-disubstituted tetrahydroisoquinolines from the corresponding amine and ketone. These rare examples of Pictet-Spengler reactions of unactivated ketones demonstrate the unique nature of calcium as a Lewis acid catalyst.     

Selenium stabilized carbenium ions. Lewis acid mediated seleno-alkylation of ketones.

Silyl enol ethers of ketones can be successfully selenoalkylated by Lewis acid activated seleno-ketals; the product β-seleno-ketones undergo interesting oxidation-deselenation reactions.