Efficient stereoselective synthesis of benzoxazines via copper-catalyzed three-component coupling reactions

A convenient one-pot synthesis of 1,4-benzoxazines via three-component coupling and subsequent O-cyclization is reported. The present reaction provides an efficient protocol to functionalized 1,4-benzoxazine derivatives in good to high yields from aldehydes, amines and alkynes. Furthermore, the O-annulation process is completely regio- and stereoselective, only the six-membered rings and its Z-isomers were obtained.     

A facile synthesis of 1,7-dicarbonyl compounds via three-component Michael addition reactions

A convenient one-pot synthesis of 1,7-dicarbonyl compounds has been accomplished by a three-component Michael addition reaction of nitromethane with two unsymmetric α,β-unsaturated carbonyl compounds in the presence of a base.     

Concise synthesis of 3,4-dihydro-1,4-benzoxazines by three-component reactions of acyl chlorides, o-aminophenols and 1,2-dichloroethane

The Cu(OAc)₂-catalyzed three-component reactions of o-aminophenols, acyl chlorides and 1,2-dichloroethane (DCE) have been established for the efficient synthesis of 3,4-dihydro-2H-benzo[b][1,4]oxazines (3,4-dihydro-1,4-benzoxazines). This method features advantages of the one-pot operation enabling N-acylation, CCl bond amidation and etherification, as well as the structural divergence of the synthesized products.     

Synthesis of highly-functionalised pyridines via hetero-Diels-Alder methodology: reaction of 3-siloxy-1-aza-1,3-butadienes with electron deficient acetylenes

The hetero-Diels-Alder reaction between 1-aza-3-siloxy-1,3-butadienes and electron deficient acetylenes is described. The reactivity of a range of α,β-unsaturated oximes and hydrazones is assessed in the synthesis of tri- and tetra-substituted pyridines bearing an oxygen functionality at C-3. Microwave irradiation has been employed to decrease the extended reaction times and increase the poor yields often associated with this reaction.     

Water-acetic acid mediated chemoselective synthesis of pyrazolines via multimolecular domino reactions of enaminones and sulfonyl hydrazines

The domino reactions between enaminones and sulfonyl hydrazines enabling novel synthesis of pyrazoline have been achieved by employing water as reaction medium and acetic acid as cheap and green additive are reported. Two new CN and one new CN bonds have been constructed during the formation of these pyrazoline scaffolds. Unlike the conventional formation of pyrazoles in the organic solvent mediated reactions of enaminones and hydrazines, the present reactions providing pyrazolines disclose new transformation pattern of enaminones by employing water as medium.     

Efficient synthesis of α-aryl serine derivatives via three-component reactions of aryldiazoacetates,anilines and formaldehyde

A three-component reaction based on trapping of ammonium ylides with formaldehyde was first reported. This reaction offers a new strategy for the synthesis of α-aryl serine derivatives and can be extended to the preparation of α-aryl threonine derivatives. Synthetic application of the three component reaction for the preparation of hydroquinoxaline derivative was also demonstrated.     

π-Annulation reactions of 4-thiazolidinone enaminones in the synthesis of fused bi- and tri-cyclic compounds

The α-C position in 4-oxo thiazolidinones functions as one of the three possible nucleophilic sites in these molecules. We used the inherent reactivity of α-C of the exocyclic double bond (a so called push pull system) to obtain bicyclic fused thiazolidinones via π-annulation cyclization. Appropriate reaction conditions to selectively activate this position and secondary nitrogen towards N,π-annulation were found. Furthermore, the intramolecular vinylogous iminium ion 6-exo-trig cyclization was used to access fused bicyclic precursors for the π-annulation in order to obtain the novel tricyclic structures stereoselectively.     

A simple and effective approach to the synthesis of rhodanine derivatives via three-component reactions in water

A facile and direct synthetic entry to rhodanine derivatives via the three-component coupling of carbon disulfide, primary amines, and acetylenic esters under neutral conditions in water is reported.     

One-pot and catalyst-free synthesis of thiosemicarbazones via multicomponent coupling reactions

A novel and efficient procedure for the synthesis of thiosemicarbazones has been achieved via a multicomponent and catalyst-free reaction of phenyl or p-chlorophenyl isothiocyanate, hydrazine, and aldehydes or ketones. The method afforded 20 thiosemicarbazones in good yields and short reaction time.     

Preparation of functionalized primary chiral amines and amides via an enantioselective three-component synthesis of propargylamines

A general preparation of functionalized primary chiral amines and amides from propargylamines has been developed. The chirality is established by an enantioselective three-component reaction of an aldehyde, a terminal alkyne and a secondary amine in the presence of copper(I) bromide/Quinap as the catalytic system leading to chiral propargylamines in high yields and enantioselectivities. Functionalization and reduction leads to various primary amines and amides.     

Vilsmeier-Haack reactions of carbonyl compounds: synthesis of substituted pyrones and pyridines

Vilsmeier-Haack reaction of substituted phenylacetones leads to the formation of conjugated iminium salts which on aqueous basic work up afford 3-formyl-4-pyrones and on ammonium acetate-induced cyclization afford 5-aryl-4-chloronicotinaldehydes in good yields.     

Synthesis of new type of Betti bases via three-component reaction of β-naphthol,cyclic amines and isatins

This work provided the first example of incorporating the oxindole moiety into the Betti bases. The new type of Betti bases were conveniently synthesized in good yields from the three-component reaction of β-naphthol, isatins and cyclic amines, such as piperidine ormorpholine, in methylene dichloride without any other catalyst.     

Iron-catalyzed three-component coupling of aldehyde, alkyne, and amine under neat conditions in air

Various iron-salts (and complexes) and especially iron(III) chloride catalyzed the three-component coupling of aldehyde, alkyne, and amine to generate propargylic amines with high efficiency under neat conditions in air. The iron-catalyzed reaction is particularly effective for reactions involving aliphatic aldehydes. The reaction is not sensitive to and occurs smoothly in water and in air. No additional co-catalyst or activator is required.     

Synthesis of new enantiomerically pure spirooxindolopyrrolizidines via a three-component asymmetric 1,3-dipolar cycloaddition reaction of azomethine ylides derived from isatin

An efficient, one-pot, three-component procedure for the synthesis of a small library of new chiral spirooxindolopyrrolizidines with high regio-, diastereo-, and enantioselectivity, from the 1,3-dipolar cycloaddition of azomethine ylides and optically active cinnamoyl oxazolidinone is described. The process occurs at room temperature in aqueous ethanol as a green solvent and in the absence of any Lewis acids. The oxazolidinone chiral auxiliary is removed in a non-destructive manner. The reaction mechanism is discussed on the basis of the assignment of the absolute configuration of the cycloadducts, and on theoretical calculations.     

Copper-catalyzed three-component reaction of imidazo[1,2-a]pyridine with elemental sulfur and arylboronic acid to produce sulfenylimidazo[1,2-a]pyridines

A copper-catalyzed three-component reaction for the synthesis of sulfenylimidazo[1,2-a]pyridines using elemental sulfur as the sulfenylating agents has been developed.     

Synthesis of isoquinolines and heterocycle-fused pyridines via three-component cascade reaction of aryl ketones, hydroxylamine, and alkynes

An efficient one-pot synthesis of isoquinolines and heterocycle-fused pyridines by three-component reaction of aryl ketones, hydroxylamine, and alkynes is developed. The reaction involves condensation of aryl ketones and hydroxylamine, rhodium(III)-catalyzed C-H bond activation of the in situ generated aryl ketone oximes, and cyclization with internal alkynes. This protocol enables rapid assembly of multisubstituted isoquinolines as well as γ-carbolines, furo[2,3-c]pyridines, thieno[2,3-c]pyridines, and benzofuro[2,3-c]pyridines from readily available substrates.     

Synthesis of 1,2-dihydroquinolin-2-ylphosphonates and 1,2-dihydroisoquinolin-1-ylphosphonates via three-component reactions

Abstract  

A facile stereoselective synthesis of 1,2-dihydroquinolin-2-ylphosphonate and 1,2-dihydroisoquinolin-1-ylphosphonate derivatives by the three-component reactions of quinoline or isoquinoline, dialkyl acetylenedicarboxylates, and hydrogen phosphonates is described.     

One-pot synthesis of 1,5,3-oxathiazepanes via the three-component condensation of primary amines,formaldehyde and 2-mercaptoethanol

The three-component condensation reaction of primary amines, formaldehyde and 2-mercaptoethanol using salts of transition and rare earth metals as catalysts was developed to obtain a new 7-membered heterocyclic structural building block, 1,5,3-oxathiazepanes, in good to excellent yields. The structure of the heterocyclic fragment was confirmed by NMR spectroscopy.     

A convenient and selective synthesis of unsymmetrical benzoins via the cyanide ion catalyzed cleavage of benzils

The cyanide ion-catalyzed cleavage of benzils is used for the generation of various ‘masked’ acyl intermediates. The reaction of these intermediates with various aldehydes furnishes the corresponding esters of unsymmetrical benzoins in very good yields. A variety of unsymmetrical benzoin derivatives are synthesized in this way, including ferrocene derivatives. The hydrolysis of benzoin esters and their subsequent oxidation affords the corresponding unsymmetrical benzoins and benzils in high yield.