Visible‐Light‐Promoted Nickel‐ and Organic‐Dye‐Cocatalyzed Formylation Reaction of Aryl Halides and Triflates and Vinyl Bromides with Diethoxyacetic Acid as a Formyl Equivalent

A simple formylation reaction of aryl halides, aryl triflates, and vinyl bromides under synergistic nickel‐ and organic‐dye‐mediated photoredox catalysis is reported. Distinct from widely used palladium‐catalyzed formylation processes, this reaction proceeds by a two‐step mechanistic sequence involving initial in situ generation of the diethoxymethyl radical from diethoxyacetic acid by a 4CzIPN‐mediated photoredox reaction. The formyl‐radical equivalent then undergoes nickel‐catalyzed substitution reactions with aryl halides and triflates and vinyl bromides to form the corresponding aldehyde products. Significantly, besides aryl bromides, less reactive aryl chlorides and triflates and vinyl halides serve as effective substrates for this process. Since the mild conditions involved in this reaction tolerate a plethora of functional groups, the process can be applied to the efficient preparation of diverse aromatic aldehydes.     

Synthesis of 3‐Aryl‐2,5‐Dihydro‐1‐Benzoxepines from Phenol via Ring‐Closing Metathesis

In this paper, the synthesis of 3‐aryl‐2,5‐dihydro‐1‐benzoxepines is described. While the reaction was started from phenol and based on the sequential reactions such as Claisen rearrangement, O‐alkylation, Wittig reaction, and ring‐closing metathesis (RCM), a series of new 3‐aryl‐1‐benzoxepines were prepared in good overall yields.     

An Efficient One‐pot Synthesis of Aryl‐substituted 1‐(Thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates via a Hantzsch Synthesis‐Knorr Reaction Sequence

The treatment of α‐bromoalkyl aryl ketones and 2‐(propan‐2‐ylidene)hydrazine carbothioamide afforded 4‐aryl‐2‐(2‐(propan‐2‐ylidene)hydrazinyl)thiazoles via a Hantzsch‐thiazole synthesis, which reacted with 4‐aryl‐2,4‐diketoesters via a sequential Knorr‐pyrazole reaction to deliver a variety of aryl‐substituted ethyl 1‐(thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates in a one‐pot fashion with moderate to high yields. The key intermediates 4‐aryl‐2,4‐diketoesters, existing as its enolic lithium salt, were synthesized in situ by a high‐yield tert‐BuOLi‐mediated Claisen condensation of alkylphenones and diethyl oxalate. This class of elegant molecule comprises aryl groups on the two different heterocyclic cores, and the configurations of two representative molecules were determined by single crystal X‐ray crystallography.     

Photosensitizer‐Free Visible‐Light‐Mediated Gold‐Catalyzed 1,2‐Difunctionalization of Alkynes

Under visible‐light irradiation, the gold‐catalyzed intermolecular difunctionalization of alkynes with aryl diazonium salts in methanol affords a variety of α‐aryl ketones in moderate to good yields. In contrast to previous reports on gold‐catalyzed reactions that involve redox cycles, no external oxidants or photosensitizers are required. The reaction proceeds smoothly under mild reaction conditions and shows broad functional‐group tolerance. Further applications of this method demonstrate the general applicability of the arylation of a vinyl gold intermediate instead of the commonly used protodemetalation step. This step provides facile access to functionalized products in one‐pot processes. With a P,N‐bidentate ligand, a stable aryl gold(III) species was obtained, which constitutes the first direct experimental evidence for the commonly postulated direct oxidative addition of an aryl diazonium salt to a pyridine phosphine gold(I) complex.     

Heck reactions of aryl halides with alk‐1‐en‐3‐ol derivatives catalysed by a tetraphosphine–palladium complex

cis,cis,cis‐1,2,3,4‐Tetrakis(diphenylphosphinomethyl)cyclopentane–[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of alk‐1‐en‐3‐ol with a variety of aryl halides. In the presence of hex‐1‐en‐3‐ol or oct‐1‐en‐3‐ol, the β‐arylated carbonyl compounds were selectively obtained. Turnover numbers up to 84 000 can be obtained for this reaction. Linalool and 2‐methylbut‐3‐en‐2‐ol led regio‐ and stereoselectively to the corresponding (E)‐1‐arylalk‐1‐en‐3‐ol derivatives. A minor electronic effect of the substituents of the aryl bromide was observed. Quite similar reaction rates were generally observed in the presence of activated aryl bromides such as bromoacetophenone and deactivated aryl bromides such as bromoanisole, indicating that, with these alkenols and this catalyst, the oxidative addition of aryl bromides to palladium is not the rate‐limiting step. It should be noted that this reaction also proceeds with sterically very congested aryl bromides such as 9‐bromoanthracene or 2,4,6‐triisopropylbromobenzene or with a vinyl bromide. On the other hand, low yields were obtained with aryl chlorides. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis of 1‐Aryl‐1H‐indazoles via a Ligand‐Free Copper‐ Catalyzed Intramolecular Amination Reaction

A general synthesis of 1‐aryl‐1‐H‐indazoles from o‐halogenated aryl aldehydes or ketones and aryl hydrazines was described. This protocol included an intermolecular condensation and a ligand‐free copper‐catalyzed intramolecular Ullmann‐type coupling reaction. This method was applied to a wide range of substrates to produce the indazole products in good yields.     

Ultrasound‐Assisted Facile Synthesis and Antimicrobial Studies of Alkanediyl‐bis‐thiazolidin‐4‐ones and Alkanediyl‐bis‐thiazinan‐4‐ones

Alkanediyl‐bis‐2‐aryl‐thiazolidin‐4‐one and alkanediyl‐bis‐2‐aryl‐1,3‐thiazinan‐4‐one derivatives have been congregated in a single step reaction of diaminoalkanes, aryl aldehydes, and sulfanyl acids in the presence of coupling agent N,N′‐dicyclohexylcarbodiimide under ultrasonic conditions. This method of constructing 4‐keto derivatives of thiazolidine and thiazinane is quick and clean besides yielding the products in quantitative yields. The spectral techniques corroborated the structures of the isolated products. Biological assay of the synthesized products has also been reported.     

One‐Pot Synthesis of 2‐Substituted 4‐Aryl‐4,5‐dihydro‐3,1‐benzoxazepines from 2‐(2‐Aminophenyl)‐1‐arylethanols via Dehydration of the Corresponding Amides

An efficient method for the preparation of 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepine derivatives under mild conditions has been developed. The reaction of 2‐(2‐aminophenyl)ethanols 1 with acid chlorides in the presence of excess Et₃N in THF at room temperature gave the corresponding N‐acylated intermediates 2 , which were dehydrated by treatment with POCl₃ to give 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepines 3 in a one‐pot reaction.     

Silylium‐Ion‐Promoted (5+1) Cycloaddition of Aryl‐Substituted Vinylcyclopropanes and Hydrosilanes Involving Aryl Migration

A transition‐metal‐free (5+1) cycloaddition of aryl‐substituted vinylcyclopropanes (VCPs) and hydrosilanes to afford silacyclohexanes is reported. Catalytic amounts of the trityl cation initiate the reaction by hydride abstraction from the hydrosilane, and further progress of the reaction is maintained by self‐regeneration of the silylium ions. The new reaction involves a [1,2] migration of an aryl group, eventually furnishing 4‐ rather than 3‐aryl‐substituted silacyclohexane derivatives as major products. Various control experiments and quantum‐chemical calculations support a mechanistic picture where a silylium ion intramolecularly stabilized by a cyclopropane ring can either undergo a kinetically favored concerted [1,2] aryl migration/ring expansion or engage in a cyclopropane‐to‐cyclopropane rearrangement.     

Transition‐Metal‐Free Formal Sonogashira Coupling and α‐Carbonyl Arylation Reactions

Transition‐metal‐free formal Sonogashira coupling and α‐carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (S_NAr) of β‐carbonyl sulfones to electron‐deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or α‐aryl carbonyl compounds. The development of these reactions is presented and, based on investigations under basic and acidic conditions, mechanisms have been proposed. To develop the formal Sonogashira coupling further, a milder, two‐step protocol is also disclosed that expands the reaction concept. The scope of these reactions is demonstrated for the synthesis of Sonogashira and α‐carbonyl arylated products from a range of electron‐deficient aryl fluorides with a variety of functional groups and aryl‐, heteroaryl‐, alkyl‐, and alkoxy‐substituted sulfone nucleophiles. These transition‐metal‐free reactions complement the metal‐catalyzed versions in terms of substitution patterns, simplicity, and reaction conditions.     

The psuedo‐michael reaction of 2‐aminoimidazolines 2. Part 1. Synthesis and structure assignment of isomeric 5(1H)‐Oxo and 7(1H)‐Oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates

The pseudo‐Michael reaction of 1‐aryl‐2‐aminoimidazolines‐2 with diethyl ethoxymethylenemalonate (DEEM) was investigated. Extensive structural studies were performed to confirm the reaction course. For derivatives with N1 aromatic substituents, it was found that the reaction course was temperature dependent. When the reaction temperature was held at ?10 °C only the formation of 1‐aryl‐7(1H)‐oxo‐2,3‐dihydroimi‐dazo[1,2‐a]pyrimidine‐6‐carboxylates ( 4 ) was observed in contrast to earlier suggestions. Under the room temperature conditions, the same reaction yielded mixtures, with varying ratio, of isomeric 1‐aryl‐7(1H)‐oxo‐ ( 4a‐4f ) and 1‐aryl‐5(1H)‐oxo‐2,3‐dihydroimidazo[1,2‐a]pyrimidine‐6‐carboxylates ( 5a‐5f ). The molecular structure of selected isomers, 4b and 5c , was confirmed by X‐ray crystallography. Frontal chro‐matography with delivery from the edge was applied for the separation of the isomeric esters. The isomer ratio of the reaction products depended on the character of the substituents on the phenyl ring. The 1‐aryl‐7(1H)‐oxo‐carboxylates ( 4a‐4f ) were preferably when the phenyl ring contained H, 4‐CH₃, 4‐OCH₃ and 3,4‐Cl₂ substituents. Chloro substitution at either position 3 or 4 in the phenyl ring favored the formation of isomers 5a‐5f . The isomer ratios were confirmed both by ¹H NMR and chromatography. The reaction of the respective hydrobromides of 1‐aryl‐2‐aminoimidazoline‐2 with DEEM, in the presence of triethylamine, gave selectively 5(1H)‐oxo‐esters ( 5a‐5f ).     

Single‐Electron‐Transfer‐Induced Coupling of Arylzinc Reagents with Aryl and Alkenyl Halides

Arylzinc reagents, prepared from aryl halides/zinc powder or aryl Grignard reagents/zinc chloride, were found to undergo coupling with aryl and alkenyl halides without the aid of transition‐metal catalysis to give biaryls and styrene derivatives, respectively. In this context, we have already reported the corresponding reaction using aryl Grignard reagents instead of arylzinc reagents. Compared with the Grignard cross‐coupling, the present reaction features high functional‐group tolerance, whereby electrophilic groups such as alkoxycarbonyl and cyano groups are compatible as substituents on both the arylzinc reagents and the aryl halides. Aryl halides receive a single electron and thereby become activated as the corresponding anion radicals, which react with arylzinc reagents, thus leading to the cross‐coupling products.     

Solvent‐free three‐component synthesis of 7‐aryl‐1,1‐dioxothieno[3,2‐b]pyran derivatives catalyzed by ammonium acetate

An efficient synthesis of 7‐aryl‐1,1‐dioxothieno[3,2‐b]pyran derivatives via the reaction of aryl aldehyde, tetrahydrothiophene‐3‐one‐1,1‐dioxide and malononitrile or ethyl 2‐cyanoacetate was performed at room temperature catalyzed by ammonium acetate under solvent‐free conditions. Compared with the conventional methods, this protocol features mild reaction conditions, high yields, and eco‐friendliness. J. Heterocyclic Chem., (2011).     

Reaction of 4,5,6‐triaminopyrimidine and 2,4,5,6‐tetraaminopyrimidine with 3‐dimethylaminopropiophenones. Synthesis of new 4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines

Several new 6‐amino‐ and 6,8‐diamino‐4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines were obtained from the reaction of 4,5,6‐triaminopyrimidine 1a and 2,4,5,6‐tetraaminopyrimidine 1b with one equivalent of 3‐dimethylaminopropiophenones 2 in absolute ethanol. Structure analysis of 6‐amino‐ and 6,8‐diamino‐4‐aryl‐2,3‐dihydropyrimido[4,5‐b][1,4]diazepines 3a‐i , determined by detailed nmr measurements, reveals a high regioselectivity of this reaction.     

Gold‐Catalyzed Formal C−C Bond Insertion Reaction of 2‐Aryl‐2‐diazoesters with 1,3‐Diketones

The transition‐metal‐catalyzed formal C−C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3‐diketones instead gives C−H bond insertion products. Herein, we report a protocol for a gold‐catalyzed formal C−C bond insertion reaction of 2‐aryl‐2‐diazoesters with 1,3‐diketones, which provides efficient access to polycarbonyl compounds with an all‐carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Brønsted acid to the reaction mixture improves the yield of the C−C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring‐opening of the resulting donor–acceptor‐type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis‐acid‐catalyzed C−C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step.     

A New Route to N‐Aryl 2‐Alkenamides,N‐Allyl N‐Aryl 2‐Alkenamides,and N‐Aryl α,β‐Unsaturated γ‐Lactams from N‐Aryl 3‐(Phenylsulfonyl)propanamides

A series of N‐aryl 2‐alkenamides were produced efficiently by treating N‐aryl 3‐(phenylsulfonyl)‐propanamides with potassium tert‐butoxide in THF at 0°C. With out isolation, it was further treated with an additional equivalent of potassium tert‐butoxide and allyl bromide to give N‐allyl N‐aryl 2‐alkenamides in one pot in good yields. Followed by a ring‐closing metathesis reaction, these N‐allyl N‐aryl 2‐alkenamides were respectively converted into corresponding N‐aryl α,β‐unsaturated γ‐lactams in moderate yields.     

Microwave‐assisted synthesis of some 1,2,4‐triazol‐5‐one derivatives

A series of 3‐alkyl(aryl)‐4‐(p‐hydroxy‐phenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 2 were obtained from the reaction of alkyl (aryl) ester ethoxycarbonyl hydrazones 1 with p‐hydroxy aniline. The reaction of 1 with 1,4‐diamino benzene (1:1) to afford 3‐alkyl(aryl)‐4‐(p‐aminophenyl)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 3 . The reaction of 3 with benzaldehyde gave 3‐alkyl(aryl)‐4‐(4′‐benzilidenamino)‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones 4 . All of the above reactions occurred under microwave heating and conventional methods. Their structures were confirmed by ¹H NMR, ¹³C NMR, IR, and elemental analyses. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:38–42, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20381     

Unexpected Ritter Reaction During Acid‐Promoted 1,3‐Dithiol‐2‐one Formation

A series of aryl‐substituted 1,3‐dithiol‐2‐ones was prepared by the Bhattacharya? Hortmann cyclization method. Unexpectedly, a Ritter reaction occurred during the acid‐catalyzed cyclization at the cyano group of the aryl substituents and 1,3‐dithiol‐2‐ones bearing a carboxy or a carboxamide group could be selectively obtained (see 1 and 2a in Scheme 1). The formation of the acid or the amide functionality was temperature‐dependent so that the one or the other group could be introduced selectively by modifying the reaction temperature.     

Ligand‐free Pd/Cu‐catalyzed decarboxylative coupling of aryl iodides with α‐oxocarboxylates

This paper describes a palladium/copper‐catalyzed decarboxylative coupling of aryl iodides with α‐oxocarboxylates. The cross‐coupling reaction gives high chemical yields of aryl ketones and has wide functional group tolerance, making the transformation an attractive alternative to the traditional cross‐coupling approaches for aryl ketones. Copyright © 2014 John Wiley & Sons, Ltd.     

Nickel‐catalyzed Kumada Cross‐coupling Reaction for the Synthesis of 2,4‐Diarylquinazolines

A series of 2,4‐diarylquinazolines have been successfully synthesized via the Ni‐catalyzed cross‐coupling reaction of quinazoline‐4‐tosylates and aryl Grignard reagents, which provided alternative straightforward approaches for the introduction of aryl groups to quinazolines at C‐4 position.