An Environmentally Benign Catalytic Method for Versatile Synthesis of 1,4-Dihydropyridines via Multicomponent Reactions

The synthesis of diverse 1,4‐dihydropyridines have been achieved via the multicomponent reactions of aldehydes, enaminones and amines. The reactions have been smoothly performed in water to provide all products with moderate to excellent yields by using lactic acid as a green catalyst.     

Nickel‐Catalyzed Borylative Coupling of Alkynes,Enones, and Bis(pinacolato)diboron as a Route to Substituted Alkenyl Boronates

Three‐component coupling reactions of an alkyne, an enone, and a diboron reagent provide access to highly substituted alkenyl boronates in good to excellent yields (see scheme). The coupling is highly regio‐ and stereoselective, and the products are amenable to further functional‐group transformations. R¹,R²=H, alkyl, aryl, CO₂Me; R³=alkyl, Ph; R⁴,R⁵=H, alkyl.

     

A Palladium(II)‐Catalyzed Synthesis of Spiroacetals through a One‐Pot Multicomponent Cascade Reaction

Functionalized spiroacetals have been easily prepared in a one‐pot three‐component coupling process that involves the reaction of pentynol derivatives, salicylaldehydes, and amines in the presence of catalytic amounts of a palladium(II) complex (see scheme). Alternatively, oxygen‐substituted spiroacetals can be obtained by using orthoesters as the third component.

     

Design and Synthesis of Pyrano[2,3-a]carbazoles by Multicomponent Reaction

A facile, efficient, three-component reaction of 2,3,4,9-tetrahydro-1H-carbazol-1-one, malononitrile, and aromatic/heteroaromatic aldehydes in dimethylformamide (DMF) gave pyrano[2,3-a]carbazoles in good yields, at reflux condition, using a catalytic amount of piperidine.     

Synthesis of Benzo[c][2,7]Naphthyridines by One-Pot Multicomponent Reaction Using Ceric(IV) Ammonium Nitrate

A new, one-pot, three-component reaction for the synthesis of benzo[c][2,7]naphthyridines has been achieved from aromatic amines, aromatic aldehydes, and N-carbethoxy-4-piperidone in the presence of a catalytic amount of ceric ammonium nitrate in good yields at room temperature. The advantages of this procedure are mild reaction conditions, low toxicity, and the use of inexpensive reagents. Apart from milder and environmentally benign conditions, this method involves a simple, reliable approach to give good yields of the desired products and is compatible with a wide range of functional groups.     

Z‐Shaped Pyrrolo[3,2‐b]pyrroles and Their Transformation into π‐Expanded Indolo[3,2‐b]indoles

Sterically hindered 1,4‐dihydropyrrolo[3,2‐b]pyrroles possessing ortho‐(arylethynyl)phenyl substituents at positions‐2 and ‐5 were efficiently synthesized through a sila‐Sonogashira reaction. These unique Z‐shaped dyes showed relatively strong fluorescence in solution. Detailed optimization revealed that, in the presence of InCl₃, these alkynes readily undergo an intramolecular double cyclization to give hexacyclic products bearing an indolo[3,2‐b]indole skeleton in remarkable yields. Steady‐state UV–visible spectroscopy revealed that upon photoexcitation, the prepared Z‐shaped alkynes undergo mostly radiative relaxation leading to high fluorescence quantum yields. In the case of 7,14‐dihydrobenzo[g]benzo[6,7]indolo[3,2‐b]indoles, we believe that the substantial planarization of geometry in the excited state, is the underlying reason for the observed large Stokes shifts. The presence of additional electron‐withdrawing groups makes it possible to further alter the photophysical properties. The two‐photon absorption cross‐section values of both families of dyes were found to be modest and the nature of the excited state responsible for two‐photon absorption appeared to be strongly affected by the presence of peripheral groups. Serendipitous synthesis of unusual double‐Z‐shaped alkyne by Sonogashira and Glaser coupling is also reported.     

Zirconium‐Mediated Multicomponent Reactions of 1,3‐Butadiynes with Ylidenemalononitriles to Form Functionalized 1,8‐Naphthyridine and Cyclopenta[b]pyridine Derivatives

Zirconocene‐mediated multicomponent reactions of 1,3‐butadiynes with ylidenemalononitriles in the absence or presence of CuCl have been developed. In the absence of CuCl, 1,3‐butadiyne couples with three molecules of ylidenemalononitriles to yield azazirconacycles bearing a hexahydro‐1,8‐naphthyridine skeleton with high stereoselectivity. In the presence of CuCl, cyclopenta[b]pyridine or cyclopenta[b]quinolin‐1‐one derivatives are obtained via transmetalation of Zr?C bond to Cu?C bond as the key reaction step. These domino‐type reactions proceed with high chemo‐, regio‐ and/or stereoselectivities, and allowing the formation of multiple C?N and C?C bonds in a single operation.     

Synthesis of Pyridazinones through the Copper(I)‐Catalyzed Multicomponent Reaction of Aldehydes,Hydrazines, and Alkynylesters

The copper‐catalyzed multicomponent cyclization reaction, which combined aldehydes, hydrazines, and alkynylesters, was applied in the synthesis of pyridazinones. The reaction was regioselective and gave only six‐membered pyridazinones in the complete absence of five‐membered pyrazoles or a regioisomeric mixture. During this investigation, the use of 2‐halobenzaldehyde as the starting material, under identical reaction conditions, gave 6‐(2‐ethoxyphenyl)pyridazinones after sequential Michael addition/1,2‐addition/Ullmann cross‐coupling reactions.     

Water Freezing as a Regiocontrol Element in the Multicomponent Assembly of Cyclic Enones

Regioselective synthesis of dialkoxy 2‐cyclopentenones and 2‐cyclohexenones with novel substitution patterns has been accomplished by the one‐pot combination of three simple starting materials (chromium carbene complex, Weinreb acetamide lithium enolate and 1‐alkoxyallenyllithium) under either anhydrous conditions or water‐promoted solidification of the reaction mixture. These results revealed an unprecedented water‐freezing effect that plays a key role to completely reverse the regioselectivity of the intramolecular carbometalation of an allene moiety.     

Catalytic Approaches to Multicomponent Reactions: A Critical Review and Perspectives on the Roles of Catalysis

In this review, we comprehensively describe catalyzed multicomponent reactions (MCRs) and the multiple roles of catalysis combined with key parameters to perform these transformations. Besides improving yields and shortening reaction times, catalysis is vital to achieving greener protocols and to furthering the MCR field of research. Considering that MCRs typically have two or more possible reaction pathways to explain the transformation, catalysis is essential for selecting a reaction route and avoiding byproduct formation. Key parameters, such as temperature, catalyst amounts and reagent quantities, were analyzed. Solvent effects, which are likely the most neglected topic in MCRs, as well as their combined roles with catalysis, are critically discussed. Stereocontrolled MCRs, rarely observed without the presence of a catalytic system, are also presented and discussed in this review. Perspectives on the use of catalytic systems for improved and greener MCRs are finally presented.     

Recent Progress in the Catalytic Synthesis of Imidazoles

Imidazole is one of the important heteroaromatic compounds that have found a broad range of uses in, for example, pharmaceutical and industrial applications. Several conventional methodologies for the synthesis of imidazole rings are known; however, they are limited in terms of substrate generality and are not always efficient. Recent studies toward the development of catalytic reactions have brought significant improvements to the preparation of imidazoles. This Focus Review highlights the very recent progress in the catalytic synthesis of imidazoles, particularly those involving the formation of five‐membered ring cores.     

Diversity‐Oriented Synthesis of Furo[3,2‐c]coumarins and Benzofuranyl Chromenones through Chemoselective Acylation/Wittig Reaction

A highly efficient and chemoselective one‐pot protocol for the diversity‐oriented synthesis of two types of coumarin‐based formal cross‐coupling adducts, furo[3,2‐c]coumarins and 3‐benzofuranyl chromenones, is described. Key attributes of the methodology are an initial chemoselective acylation of functionalized phosphorus zwitterions and a subsequent chemoselective intramolecular Wittig reaction that preferentially resulted in one of the two coumarin derivatives in high yield, depending on relative reactivities and the addition sequence of the acylating agents.     

Mg-Al Hydrotalcite as a First Heterogeneous Basic Catalyst for the Synthesis of 4H-Pyrano[2,3-c]pyrazoles Through a Four-Component Reaction

Mg/Al hydrotalcite acts as an efficient heterogeneous basic catalyst for the synthesis of 4H-pyrano[2,3-c]pyrazoles via a multicomponent reaction of aromatic hydrazine hydrate, ethyl acetoacetate, aldehydes, and malononitrile in ethanol at ambient temperature. The hydrotalcite catalyst was easily separated from the reaction mixture and can be reused.

Iodine-Catalyzed,Multicomponent, One-Pot Synthesis of 5-Aryl-5,8-dihydrotetrazolo[1,5-a]pyrimidine-7-carboxylic Acids

A series of 5-aryl-5,8-dihydrotetrazolo[1,5-a]pyrimidine-7-carboxylic acids (4) were synthesized from 5-aminotetrazole, pyruvic acid, and aromatic aldehydes in one pot in the presence of I₂ with moderate to good yields. Operational simplicity, mild reaction conditions, and ecofriendly procedure make this novel protocol a promising alternative for the fusion of tetrazolopyrimidines. The structures of the products were proved by ¹H and ¹³C NMR spectroscopy, liquid chromatography–mass spectrometry, and elemental analysis.