Chemical Transformations of Tetracyclo[3.3.1.1<Superscript>3,7</Superscript>.0<Superscript>1,3</Superscript>]decane (1,3-Dehydroadamantane): VI. Reactions of 1,3-Dehydroadamantane with Carboxylic Acid Chlorides

1,3-Dehydroadamantane reacted with saturated carboxylic acid chlorides to give the corresponding 1-acyl-3-chloroadmantanes as the major products. In some cases, minor products of insertion into the C^α–H bond of acyl chloride were formed. The reactions of 1,3-dehydroadamantane with aromatic (heteroaromatic) carboxylic acid chlorides selectively afforded aryl (hetaryl) 3-chloroadamantan-1-yl ketones. The described reactions provide a synthetic route to difficultly accessible alkyl (aryl) ketones containing a 3-chloroadamantan- 1-yl group in one step under mild conditions with high yields.     

Silver compounds in synthetic chemistry : Part 5: Selective syntheses of trifluoromethylketones, RCOCF3, from trifluoromethylsilver, AgCF3, and corresponding acyl chlorides, RCOCl

Trifluoromethylketones of aromatics, heteroaromatics and olefins are formed selectively from reactions of trifluoromethylsilver and the corresponding carboxylic acid chlorides in moderate to excellent yields. The conditions chosen are dependent on the nature of the acyl chloride. Attempts to prepare alkyl(trifluoromethyl)ketones yielded product mixtures of the corresponding acyl fluorides, trifluoromethyl-, pentafluoroethyl- and n-heptafluoropropyl ketones.     

Ketones from Nickel‐Catalyzed Decarboxylative,Non‐Symmetric Cross‐Electrophile Coupling of Carboxylic Acid Esters

Synthesis of the C?C bonds of ketones relies upon one high‐availability reagent (carboxylic acids) and one low‐availability reagent (organometallic reagents or alkyl iodides). We demonstrate here a ketone synthesis that couples two different carboxylic acid esters, N‐hydroxyphthalimide esters and S‐2‐pyridyl thioesters, to form aryl alkyl and dialkyl ketones in high yields. The keys to this approach are the use of a nickel catalyst with an electron‐poor bipyridine or terpyridine ligand, a THF/DMA mixed solvent system, and ZnCl₂ to enhance the reactivity of the NHP ester. The resulting reaction can be used to form ketones that have previously been difficult to access, such as hindered tertiary/tertiary ketones with strained rings and ketones with α‐heteroatoms. The conditions can be employed in the coupling of complex fragments, including a 20‐mer peptide fragment analog of Exendin(9–39) on solid support.     

Ketones from Nickel‐Catalyzed Decarboxylative,Non‐Symmetric Cross‐Electrophile Coupling of Carboxylic Acid Esters

Synthesis of the C?C bonds of ketones relies upon one high‐availability reagent (carboxylic acids) and one low‐availability reagent (organometallic reagents or alkyl iodides). We demonstrate here a ketone synthesis that couples two different carboxylic acid esters, N‐hydroxyphthalimide esters and S‐2‐pyridyl thioesters, to form aryl alkyl and dialkyl ketones in high yields. The keys to this approach are the use of a nickel catalyst with an electron‐poor bipyridine or terpyridine ligand, a THF/DMA mixed solvent system, and ZnCl₂ to enhance the reactivity of the NHP ester. The resulting reaction can be used to form ketones that have previously been difficult to access, such as hindered tertiary/tertiary ketones with strained rings and ketones with α‐heteroatoms. The conditions can be employed in the coupling of complex fragments, including a 20‐mer peptide fragment analog of Exendin(9–39) on solid support.     

Reactions of gem-dibromo compounds with trialkylmagnesate reagents to yield alkylated organomagnesium compounds

The reaction of gem-dibromocyclopropanes 5 with nBu(3)MgLi affords butylated cyclopropylmagnesium species that can be trapped with various electrophiles. The reaction of dibromomethylsilanes 12 requires the addition of a catalytic amount of CuCN small middle dot2 LiCl for smooth migration of the alkyl groups. The resultant alpha-silylpentylmagnesium compounds 16 react with electrophiles, such as acyl chlorides or alpha,beta-unsaturated ketones to afford alpha- or gamma-silyl ketones, respectively. Treatment of dibromodisilylmethanes with Me(3)MgLi yields 1-bromo-1,1-disilylethanes 25 that can be converted into 1,1-disilylethenes 29 by dehydrobromination.     

Indium-catalyzed coupling reaction between silyl enolates and alkyl chlorides or alkyl ethers

The coupling reactions of alkyl chlorides with silyl enolates catalyzed by InBr₃, and the coupling reactions of alkyl ethers with silyl enolates catalyzed by the combined Lewis acid of InBr₃/Me₃SiBr are described. In both reaction systems, various types of silyl enolates were used to give corresponding α-alkylated esters, ketones, carboxylic acids, amides, thioesters, and aldehydes.     

Direct formation of functionalized ketones via the coupling of functionalized organocopper reagents with acid chlorides

Highly reactive copper solutions have been prepared by the lithium naphthalide reduction of a copper(I) iodide/triphenyl-phosphine complex. These copper solutions react rapidly with functionalized alkyl halides to give organocopper reagents which have been effectively trapped with acid chlorides giving functionalized ketones in good yields. Ester, nitrile, chloride, remote epoxide, and, to some degree, ketone groups can be tolerated by this approach.     

Zur Kenntnis der Substitutionsprodukte der (2H)-Imidazol-4(3H)-thione und 2H-Imidazol-4(3H)-one

2H-Imidazole-4(3H)-thiones (a), available from methyl alkyl and methyl aryl ketones with sulfur and ammonia, react via their corresponding N-sodium compounds or in presence of tert. amines with alkyl and aryl carboxylic acid chlorides to give the corresponding intensely coloured (orange to violett) cryst. 3-acyl-2H-imidazole-4(3H)-thiones4 a-q and6–26. With dicarboxylic acid dichlorides the colourless cryst. N,N′-diacyl-bis-3-imidazoline-5-thiones5 a-d and27–32 are obtained. With carbamic acid chlorides and chloroformic acid esters the corresponding urea (33–35) and urethane derivatives36, 37 are formed. In an analogous way 2H-imidazol-4(3H)-ones react with acid chlorides to 3-acyl-2-imidazol-4(3H)-ones (44–50), which can also be obtained by treating the corresponding 3-acyl-2H-imidazole-4(3H)-thione with KMnO₄.     

Photoinduced Electron Transfer from Xanthates to Acyl Azoliums: Divergent Ketone Synthesis via N-Heterocyclic Carbene Catalysis

Considering the prevalence of alcohols and carboxylic acids, their fragment cross-coupling reactions could hold significant implications in organic synthesis. Herein, we report a versatile method for synthesizing a diverse range of ketones from alcohols and carboxylic acid derivatives via N-heterocyclic carbene (NHC) catalysis. Mechanistic investigations revealed that photoexcited xanthates and acyl azoliums undergo single electron transfer (SET) under photocatalyst-free conditions, generating NHC-derived ketyl radicals and alkyl radicals. These open-shell intermediates subsequently undergo the radical-radical cross-coupling reaction, yielding valuable ketones. Furthermore, this approach can be employed in three-component reactions involving alkenes and enynes, resulting in structurally diverse cross-coupled ketones. The unified strategy offers a unique opportunity for the fragment coupling of a diverse range of alcohols and carboxylic acid derivatives, accommodating diverse functional groups even in complex settings.     

Nickel‐Catalyzed Synthesis of Dialkyl Ketones from the Coupling of N‐Alkyl Pyridinium Salts with Activated Carboxylic Acids

While ketones are among the most versatile functional groups, their synthesis remains reliant upon reactive and low‐abundance starting materials. In contrast, amide formation is the most‐used bond‐construction method in medicinal chemistry because the chemistry is reliable and draws upon large and diverse substrate pools. A new method for the synthesis of ketones is presented here that draws from the same substrates used for amide bond synthesis: amines and carboxylic acids. A nickel terpyridine catalyst couples N‐alkyl pyridinium salts with in situ formed carboxylic acid fluorides or 2‐pyridyl esters under reducing conditions (Mn metal). The reaction has a broad scope, as demonstrated by the synthesis of 35 different ketones bearing a wide variety of functional groups with an average yield of 60±16 %. This approach is capable of coupling diverse substrates, including pharmaceutical intermediates, to rapidly form complex ketones.     

An atom-efficient palladium-catalyzed cross-coupling reaction of triarylbismuths with acid chlorides: synthesis of diaryl and alkyl aryl ketones

The cross-coupling reaction of triarylbismuths with acid chlorides using a catalytic amount of PdCl₂/PPh₃ afforded the corresponding ketones in high yields. The reactions of aromatic and aliphatic acid chlorides occurred with atom efficiency, as 3 equiv of acid chlorides coupled effectively with 1 equiv of triarylbismuths to yield 3 equiv of the corresponding diaryl and alkyl aryl ketones.     

A convenient and efficient unsymmetrical ketone synthesis from acid chlorides and alkyl iodides catalyzed by palladium

Unsymmetrical ketones are prepared in good or excellent yields by a palladium catalysed coupling reaction of acid chlorides and alkyl iodides mediated by Zn-Cu couple.     

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.     

Solid-phase synthesis of substituted 3-amino-3′-carboxy-tetrahydrocarbazoles

Two related solid-phase synthesis routes have been developed allowing the synthesis of 3-amino-3′-carboxy substituted tetrahydrocarbazole derivatives. Diversity can be introduced at the amino and carboxy functionalities and at the nitrogen and the aromatic ring of the tetrahydrocarbazole moiety. Both routes rely on Fmoc-protected 1-amino-4-oxocyclohexanone carboxylic acid as central core element. Derivatization of the carboxy function is achieved with amines, derivatization of the amino functionality is possible by reaction with alkyl halides, isocyanates, activated alcohols, sulfonic acid chlorides or carboxylic acids. The tetrahydrocarbazole scaffold is generated by Fischer indole cyclization with phenyl hydrazine derivatives, thereby introducing diversity in the aromatic moiety. N-Alkylation at the indole nitrogen with alkyl halides delivers N-substituted derivatives.     

Synthesis of ketones of the barene series

Conclusions A method was proposed for synthesizing ketones of the barene series by the reaction of carboxylic acid chlorides with lithium derivatives of barenes.     

An Improved Procedure for the Conversion of Carbonyl Compounds to α,β-Unsaturated Carboxylic Acids

The two carbon homologation of aldehydes and ketones to give α,β-unsaturated carboxylic acids is often carried out via the corresponding ester using metallated phosphonate reagents² (1) (Equation I). When alkyl esters (la) are employed problems are sometimes encountered in the hydrolysis step due to acid or base sensitivity but these problems can be overcome using the silyl ester (lb)³.     

Ketone formation via mild nickel-catalyzed reductive coupling of alkyl halides with aryl acid chlorides

The present work highlights unprecedented Ni-catalyzed reductive coupling of unactivated alkyl iodides with aryl acid chlorides to efficiently generate alkyl aryl ketones under mild conditions.     

New flexible synthesis of pyrazoles with different,functionalized substituents at C3 and C5

Syntheses of pyrazoles featuring a functionalized side chain attached to carbon 3 and varying alkyl and aryl substituents attached to carbon 5 are presented. Installation of R = methyl, isopropyl, tert-butyl, adamantyl, or phenyl groups at C5 is reported here, starting by coupling protected alkynols with acid chlorides RCOCl, forming alkynyl ketones, which are reacted with hydrazine to form the pyrazole nucleus. Alcohol deprotection and conversion to a chloride gave 5-substituted 3-(chloromethyl)- or 3-(2-chloroethyl)pyrazoles. This sequence can be done within 2 d on a 30 g scale in excellent overall yield. Through nucleophilic substitution reactions, the chlorides are useful precursors to other polyfunctional pyrazoles. In the work here, derivatives with side chains LCH(2)- and LCH(2)CH(2)- at C3 (L = thioether or phosphine) were made as ligands. The significance of the ligands made here is that by placing a ligating side chain on a ring carbon (C3), rather than on a ring nitrogen, the ring nitrogen not bound to the metal and its attached proton will be available for hydrogen bonding, depending on the steric environment created by R at C5.     

2-Halogenoethyl and 2-halogenoethylthiol esters of furan series carboxylic acids

The corresponding 2-chloroethyl (2-chloroethylthiol) esters are synthesized by the action of ethylene chlorohydrin (chloroethylmercaptan) on the acid chlorides of 5-nitrofuran carboxylic acid and 3-(5-nitrofuryl-2)acrylic acid. The acid chlorides of benzoic, furan carboxylic, and 3-(furyl-2)-acryllc acids react with ethylene sulfide, to give 2-chloroethyl esters of those acids. Ethylene oxide does not react with the acid chlorides of benzoic acid and furan series carboxylic acids either at room temperature or on heating at 50° for 1 hour.     

Action of (2-benzothiazolyl)methyllithium with organic polar functions

(2-Benzothiazolyl)methyllithium reacts quickly at low temperature (-78°) with a variety of organic electrophiles like aldehydes, ketones, carboxylic esters, nitriles and acyl chlorides. Such reactions lead to an easy introduction of alcohol, keto-enol or amine-enamine functional groups in extracyclic position with a stereoselective preference. These polyfunctional compounds whose synthesis is difficult by other pathways, are interesting, in particular, because of their ability to form intramolecular hydrogen bonds.