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The Z-selective halosulfonylation of terminal alkynes has been achieved via the halosulfonylation of terminal alkynes by using sulfonohydrazides and copper(I) halides (CuI, CuBr and CuCl), which enables the generally applicable synthesis of halogenated vinyl sulfones with satisfactory efficiency.

An unprecedented domino reaction involving primary enaminones/enaminoesters and aldehydes has been developed for the synthesis of fully substituted pyridines. The construction of the products has been accomplished via the cascade generation of two C–C and one C–N bond by simply using TfOH as a promoter.

The syntheses of β,β-diaryl aryl propiophenones have been realized via palladium-catalyzed domino reactions of dimethyl amino functionalized enaminones and aryl boronic acids. This is the first example of transition metal-catalyzed enaminone C–N bond conversion for the generation of a new C–C(aryl) structure.

The intramolecular C–N bond forming cross coupling reactions on the enaminones has been achieved for the synthesis of imidazole[1,2-a]pyridines via copper-catalyzed C(sp2)–H amination. This protocol provides a new route for the synthesis of 2-unsubstituted imidazole[1,2-a]pyridines via easily available starting materials.

Carbonyl-forming reactions are a class of fundamental transformations in organic chemistry. Guided by the current importance of environmentally benign metal-free catalysis and synthesis, herein we review recent advances in carbonyl-generation reactions based on alkene C=C double oxygenation as well as related cascade reactions in the synthesis of diverse organic products. The content of this focus review consists of two important but different reaction models: oxygenation based on full C=C double-bond cleavage and oxygenation based on partial C=C double-bond cleavage.

The Pd-catalyzed C−H arylation of phenylacetamides in the γ position was realized for the first time by means of a domino process consisting of in situ directing group installation and C−H arylation. Unprecedented tunable selectivity between di- and monoactivation of the two identical γ-C−H bonds was achieved by modifying the reaction conditions; this is a distinct feature of this one-pot procedure for the C−H-activation-based synthesis of diverse amides.

Electron-deficient enamines such as enaminones and enaminoesters are moieties showing widespread application in organic synthesis. Among the various available electron-deficient enamines, the N,N-disubstituted amino-functionalized ones (tertiary enamines) represent a class of special enamines with distinct properties and important applications. Based on our longstanding interest in exploring novel synthetic methods using electron-deficient tertiary enamines, we present herein the research advances in organic synthesis via domino reactions making use of the combinatorial C-N, C=C, C-H, and other bond transformations of electron-deficient tertiary enamines.

The title diketones are prepared from enaminones and aminothiophenols by the cascade reaction involving partial cleavage of the C=C bond.

Copper catalysis has been known as a powerful tool for its ubiquitous application in organic synthesis. One of the fundamental utilities of copper catalysis is in the C–N bond formation by using carbon sources and nitrogen functional groups such as amides. In this review, the recent progress in the amidation reactions employing copper-catalyzed C–H amidation is summarized.

An environmentally benign multicomponent synthetic method has been realized for the diastereoselective construction of fused tetrahydropyridines. Structurally diverse products have been acquired with generally good yields via the assembly of simple starting materials, enaminones or nitroenamines, o-aminophenols, and cinnamaldehydes, in the presence of lactic acid in water–ethanol media.

The construction of 1,5-disubstituted 1,2,3-triazoles has been effected through the cascade dual C-N bond formation, N-N bond formation and an acyl migration-based C-C bond formation via the three-component reactions of enaminones, tosylhydrazine and primary amines. This metal- and azide-free, regioselective synthetic method proceeds in the presence of only molecular iodine.

An organocatalytic cascade reaction involving the incorporation of alkyl propiolates and primary amines has been realized for the facile synthesis of 1,4-dihydropyridines (1,4-DHPs) bearing a C4 acetate fragment. This method allows rapid and atom economical generation of N -aryl, N -alkyl, and NH 1,4-DHPs with moderate to excellent yields.

Title compounds [(IV) and (VI)] are synthesized through environmentally benign multicomponent reactions in aqueous medium using lactic acid as a green catalyst.

A concise multicomponent one-step method for the synthesis of 2,6-biarylated (IV),(VI) or 6-arylated benzamides (VIII) starting from 8-aminoquinoline, benzoyl chlorides, and various iodobenzenes is established.

Indole synthesis via copper-catalyzed one-pot reactions of o-iodophenols, acyl chlorides, and Wittig reagents is reported.

A three-component synthetic method involving the assembly of enals, N,N-disubstituted enaminones and 2-aminopyridines has been designed, which leads to the facile and regioselective synthesis of 1,2-dihydropyridines (1,2-DHPs) with broad scope and generally good yields in the presence of simple acid catalysts.

The title compounds are obtained with high diversity involving the cascade formation of a new C=C bond and a C(sp2)—O bond using glucose as a green ligand.

Numerousbenefits have been given by the classic synthetic toolbox,however, the fatal restriction within these heavy metal-cata-lyzed syntheses is the contamination by trace metals producedin the work-up, which prevents this transformation from facileapplication in biologically relevant investigations. In thisregard, the metal-free AAC reactions have emerged as anothermilestone. Previously, these metal-free protocols were de-signed based on the employment of alternative reaction part-ners of alkynes to incorporate azides.

The multicomponent reaction provides a one-step access to 3,4,5-trisubstituted pyridines and succeeds using aryl aldehydes, but fails with alkyl aldehydes.

One-pot reactions involving acyl chlorides, phosphorus ylides, and o-iodophenols with copper catalysis have been established for the rapid synthesis of functionalized benzofurans. With all of these easily available and stable reactants, the construction of the target products has been accomplished via tandem transformations involving a key C–C coupling, leading to the formation of one C(sp2)–C bond, one C(sp2)–O bond, and one C═C bond.

The copper-catalyzed cascade reaction of enaminones and ammonium chloride leads to the unprecedented synthesis of 4-unsubstituted pyridines of both symmetrical and unsymmetrical structures.

The selectivity of the title reaction depends on the choice of the amine component [(II) and (IX)].

Title compounds (V) are prepared via the multicomponent reaction of o-iodophenols (I), in situ generated allenes, and dichloromethane (IV).

Various title compounds (III), (VI), (IX) are obtained by C-S cross coupling reactions between electron deficient heteroaryl thiols and aryl halides.

The C-3 sulfenylation reaction of indoles has been achieved under mild reaction conditions by simply employing NaOH as promoter and thiols as thiolating reagents. This simple method allows for easy and rapid synthesis of various 3-sulfenylated indoles with generally good to excellent yields. Primary attempts in scale-up synthesis give satisfactory result.

Ethyl lactate is found to be an excellent medium for Glaser-type homo- and cross-coupling reactions of terminal alkynes furnishing the corresponding conjugated diynes in good to excellent yields.

A three-component reaction of aminoalcohols, propiolic esters, and α,β-unsaturated aldehydes is developed to permit the highly diastereoselective synthesis of a range of tetrahydropyridine fused heterocycles.

Cyclotrimerization reactions of both enaminones and electron deficient terminal alkynes are efficiently performed in water in the presence of lactic acid.

Selective bis-sulfenylation reactions of aryl dihalides have been achieved by copper-catalyzed C–S coupling reactions under mild conditions of refluxing EtOH (80 °C). Employment of disulfides as thiolating reagents enables the production of various bis(phenylthio)benzenes with excellent selectivity, and no products from mono C–S coupling are isolated.

A number of symmetrical N-substituted or N-unsubstituted 1,4-dihydropyridines are obtained by multicomponent reactions of various aromatic aldehydes, electron deficient alkynes, and NH4OAc or amines, respectively

The title reaction gives rise to the formation of a broad array of iodine-functionalized diarylsulfides (III) (22 examples).

The title reaction exhibits good functional group compatibility and provides a convenient approach for the synthesis of symmetrical and unsymmetrical diynes.

An efficient and green approach for the highly stereoselective synthesis of (Z)-enaminones (III) is given.

Isatins are well-known carbonyl electrophiles which allow a vast number of reactions initiated by nucleophilic attack on the C3 carbonyl group when used as starting materials. The most notable feature of isatins is that they serve as donors of oxindole fragments and furnish spirocyclic products in most cases. Because of their high reactivity and easy availability, isatins have been broadly used as building blocks in the synthesis of structurally complex and diverse heterocyclic compounds in multicomponent reactions (MCRs). Recent advances in diversity oriented synthesis with isatin-based MCRs are discussed in this Focus Review and are classified into different sections based on the key transformation involved in the reactions, such as 1,3-dipolar cycloaddition, Knoevenagel reaction, ring-opening of isatins and so on.

A series of tetrahydropyridin-2-ols (III) is obtained by a Michael addition-hemiaminalization reaction sequence of enaminones (I) with enals (II).

Active methylene compounds are a major class of reaction partners for C-C bond formation with sp(2) C-X (X = halide) fragments. As one of the most-classical versions of the Ullmann-type coupling reaction, activated-methylene-based C-C coupling reactions have been efficiently employed in a large number of syntheses. Although this type of reaction has long relied on noble-metal catalysis, the renaissance of copper catalysis at the end of last century has led to dramatic developments in Ullmann C-C coupling reactions. Owing to its low cost, abundance, as well as excellent catalytic activity, the exceptional atom economy of copper catalysis is gaining widespread attention in various organic synthesis. This review summarizes the advances in copper-catalyzed intermolecular and intramolecular C-C coupling reactions that use activated methylene species as well as in tandem reactions that are initiated by this transformation.

Organosillicon reagents have been found as versatile catalysts or promoters for a broad range of organic reactions due to their special properties of multifunction. An important application of organosilicon reagents is in the research field of multicomponent reac- tions (MCRs), which provides a vast number of practical synthesis for different molecular libraries. We present in this review the recent research progress of MCRs employing organosillicon reagents as catalysts or promoters for the first time.

Copper-catalyzed cross-coupling reactions which lead to the formation of C–N, C–O, C–S and C–C bonds have been recognized as one of the most useful strategies in synthetic organic chemistry. During past decades, important breakthroughs in the study of Cu-catalyzed coupling processes demonstrated that Cu-catalyzed reactions are broadly applicable to a variety of research fields related to organic synthesis. Representatively, employing these coupling transformations as key steps, a large number of tandem reactions have been developed for the construction of various heterocyclic compounds. These tactics share the advantages of high atom economics of tandem reactions as well as the broad tolerance of Cu-catalyst systems. Therefore, Cu-catalyzed C–X (X = N, O, S, C) coupling transformation-initiated tandem reactions were quickly recognized as a strategy with great potential for synthesizing heterocyclic compounds and gained worldwide attention. In this review, recent research progress in heterocycle syntheses using tandem reactions initiated by copper-catalyzed coupling transformations, including C–N, C–O, C–S as well as C–C coupling processes are summarized.

The O-arylation of o-enaminone functionalized phenols, namely, (E)-3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-ones, has been achieved via a self-promoted process in the presence of CuI, which provided a class of new biaryl ethers bearing a reactive enaminone fragment. The reactions were performed under mild conditions and the functionalized biaryl ether products have been found as useful building blocks for the assembly of heterocyclic compounds.

A highly efficient and catalyst-free method for the synthesis of substituted thiourea derivatives is presented. The synthesis is performed through the reaction of thiazolidine-2-thiones with various amines in water. A sound number of thioureas with both unsymmetrical and symmetrical architectures have been obtained in good to excellent yields.

The reaction of enaminones (I), benzaldehydes (II), anilines (III), and thiourea proceeds in the manner of specific diastereoselectivity with all-cis relationship of the substituents at the resulting pyrimidinethiones.

A Broensted acid catalyzed redox amination of indoline with aldehydes for the synthesis of N-alkylindoles (III) proceeds via intramolecular hydride transfer.

Copper-catalyzed reaction of arenethiols (I) with aryl iodides (II) and bromides (IV) proceeds with thioether formation and concomitant ortho-hydroxylation of the thiol-derived aryl ring.

Microwave irradiation is found to efficiently promote the three-component reaction of aromatic aldehydes, thiourea and vinylbenzenes in the presence of Tms-Cl.