Three-component domino reaction synthesis of highly functionalized bicyclic pyrrole derivatives

An efficient one-pot synthesis of highly functionalized bicyclic pyrrole derivatives by a three-component domino reaction of heterocyclic ketene aminals (HKAs), arylglyoxal monohydrate, and indoles in ethanol medium catalyzed by acetic acid is described. In this procedure, three sigma bonds were formed simultaneously. The present synthesis features excellent regio-selectivity, easy purification as well as simple starting materials.     

Copper catalyzed synthesis of highly substituted pyrrole and isoindole derivatives

We have developed an efficient synthesis of highly substituted pyrrole and isoindole derivatives using copper(I) catalyst. This methodology is helpful for the synthesis of some quinones bearing annealed N-heterocyclic natural products.     

Organocatalytic domino reactions: synthesis of densely functionalized cyclohexene derivatives

A highly enantioselective domino reaction of α,β-unsaturated aldehydes and 4-acetyl-5-oxohexanal catalyzed by a chiral secondary amine catalyst has been developed, providing an efficient synthetic approach for the synthesis of densely functionalized chiral cyclohexene derivatives with high yields (up to 96%) and enantioselectivities (up to 97% ee) under mild conditions.     

One-pot synthesis of 5-amino 4-cyano pyrrole derivatives

One-pot synthesis of 5-amino 4-cyano pyrrole derivatives is herein disclosed. The described method consists of four steps and gives new pyrrole derivatives in moderate to good yields. This synthesis can be used for a large scale preparation.     

Asymmetric catalytic Mannich reactions catalyzed by urea derivatives: enantioselective synthesis of beta-aryl-beta-amino acids

Highly enantioselective addition reactions between silyl ketene acetals and N-Boc aldimines are catalyzed by the thiourea-based catalyst 1c. Extraordinary scope is observed in this methodology with regard to the imine substrate, with aryl and heteroaromatic derivatives generally affording nearly quantitative yields of beta-amino ester product in up to 98% enantioselectivity.     

Supramolecular synthesis of coumarin derivatives catalyzed by a coordination-assembled cage in aqueous solution

A self-assembled Pd_4L_2 cage is employed as a water-soluble molecular flask for the synthesis of functionalized coumarins from a series of salicylaldehyde derivatives and cyanoacetates/malononitrile. The catalytic reaction features mild aqueous conditions and broad substrate scope. Crystal structures of the host-guest complexes for two substrates and one analogous intermediate have been obtained, shedding light on the supramolecular reaction mechanism. Michaelis-Menten kinetic studies were performed in one typical case, revealing that the rate of product formation has been enhanced by over 23-fold in contrast to the background reaction without cage. Moreover, the same reaction catalyzed by a smaller Pd_6L_4 cage gives a mixture of products and much lower yields, suggesting that fine-tuning on the size and symmetry of the cages' cavity is crucial for their applications in supramolecular catalysis.     

Microwave assisted synthesis of dihydropyrrole by AgOAc catalyzed intramolecular cyclization reaction of homopropargyl amine

A series of 5-aryl dihydropyrrole was synthesized from the intramolecular cyclization reaction of homopropargyl amine in the presence of AgOAc as catalyst under microwave irradiation reaction conditions. The homopropargyl amine was prepared by the reaction of propargyl bromide with N-tosyl aldimine under a sonochemical Barbier-type reaction condition. Further aromatization reaction of 5-aryl dihydropyrrole in KOtBu/DMSO can afford 2-aryl pyrrole under microwave irradiation reaction conditions.     

A novel multicomponent Zr-catalyzed synthesis of functionalized pyrano[3,2-b]pyrrole derivatives

A novel, efficient, and rapid procedure, one-pot condensation of 3-hydroxypyrrole, malononitrile, and aromatic aldehydes, with 10 mol % bis[N-(3,5-dicumylsalicylidene)anthracylaminato]zirconium(IV) dichloride as catalyst, in the presence of ultrasonic irradiation, has been developed for synthesis of 5-amino-7-aryl-6-cyano-4H-pyrano[3,2-b]pyrrole derivatives.     

Cyclization of N-benzyl cyanoacetamide: Novel synthesis and biological activity of pyrrole,pyrimidine, and pyran derivatives

Heteroannulation of N-Benzyl cyanoacetamide 1 to a new series of heterocycles has been developed. Thus, reaction of 1 with different polarized π systems afforded pyrrolo 4 , pyridone 6 , pyridine 8 , and diazapene 10 derivatives, respectively. N-Benzyl cyanoacetamide that undergo condensation reaction with salicylaldehyde yielded pyran derivative 11 . Nitrosation of 11 furnished condensed pyran 13 . Compound 11 reacted with benzaldehyde, carbon disulfide (cyclizing agent), and ammonium thiocyanate to provide pyrane 17 , thiazine 18 , and thiourea 20 derivatives, respectively. Cinnamoyl isothiocyanate was reacted with compound 11 to produce non-isolable thiourea derivative 21 . The newly synthesized compounds have been characterized by infrared (IR), proton nuclear magnetic resonance (¹H NMR), and carbon nuclear magnetic resonance (¹³C NMR) spectral data. The compounds were then evaluated for antibacterial and anticancer activities.     

Iodine catalyzed one-pot five-component reactions for direct synthesis of densely functionalized piperidines

A simple and convenient one-pot multicomponent reaction (MCR) has been developed for the synthesis of highly functionalized piperidines catalyzed by molecular iodine. This strategy demonstrated five-component reactions of 1,3-dicarbonyl compounds, amines and aromatic aldehydes in methanol using 10 mol % of iodine at room temperature. This methodology provides an alternative approach for easy access of highly and fully substituted piperidines in moderate to good yields using three readily available starting materials. Notably, this method is mild, cheap, straight forward, applicable to broad range of substrates and environmentally friendly as compared to the existing methods. Synthetic and mechanistic studies are presented here.     

Aldol reactions catalyzed by l-proline functionalized polymeric nanoreactors in water

The use of functional core-shell micelles as asymmetric catalytic nanoreactors for organic reactions in water is presented. An unprecedented increase in rate of reaction was achieved, which is proposed to be associated with the ability of the nanostructures to effectively concentrate the reagents in the catalytically active micelle core.     

One-pot synthesis of new functionalized 4H-chromen-4-ylidene derivatives

A simple synthesis of new series of functionalized chromene derivatives through an efficient, one-pot, multicomponent reaction of nitroketene N,S-acetals, salicylaldehydes, and cyanoacetohydrazide in ethanol at ambient temperature in good to high yields is reported. This novel efficient method has the advantages of mild reaction conditions, absence of catalyst, simple work-up, and the non-chromatographic purification of products.     

Facile one-pot synthesis of novel highly functionalized dihydro-1H-pyrrole derivatives catalyzed by molecular iodine

An efficient, environmentally benign and molecular iodine promoted protocol was described for cascade synthesis of two kinds of novel dihydro-1H-pyrrole derivatives, 5 and 7. Compounds 5 were prepared via four-component reaction between diethyl acetylenedicarboxylate (DEAD), aromatic amines and phenylglyoxal monohydrate catalyzed by 10 mol% of iodine in ethanol at room temperature. In addition, using same reaction conditions, a three-component reaction between (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), aromatic amines and arylglyoxal monohydrate was performed to access product 7. These transformations apparently proceed through an imine intermediate followed by iodine induced Mannich reaction and subsequent intra-molecular cyclization sequences. The protocol involves the formation of CN, CC and OH bonds leading to the preparation of a hexa substituted five membered ring with two stereo centres. The syntheses avoid the use of traditional column chromatography and recrystallization purification methods and, hence, follow the group-assisted purification (GAP) chemistry process.     

Cyclization of functionalized ketene-N,S-acetals to substituted pyrroles: applications in the synthesis of marine pyrrole alkaloids

α-Oxoketene-N,S-acetals, prepared by the reaction of alkyl glycinates with β-oxodithiocarboxylates followed by alkylation, underwent cyclization in the presence of the Vilsmeier reagent to afford alkyl 3-aryl-4-formyl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates in excellent yields. When the reaction was extended to β-oxodithiocarboxylates derived from deoxyanisoin, 3,4-diarylpyrrole-2-carboxylates, the key intermediates in the synthesis of lukianol A and lamellarin Q were formed.     

Remarkable solvent effect in Barton-Zard pyrrole synthesis: application in an efficient one-step synthesis of pyrrole derivatives

A unique solvent effect encountered in the Barton-Zard pyrrole synthesis was exploited to develop an efficient synthesis of pyrrole-2-esters. The chemistry was extended to a one-pot synthesis of pyrrole-2,4-dicarboxylates.     

Enantioselective oxidative biaryl coupling reactions catalyzed by 1,5-diazadecalin metal complexes: efficient formation of chiral functionalized BINOL derivatives

Chiral 1,5-diaza-cis-decalins have been examined as ligands in the enantioselective oxidative biaryl coupling of substituted 2-naphthol derivatives. Under the optimal conditions employing 2.5-10 mol % of a 1,5-diaza-cis-decalin copper(II) catalyst with oxygen as the oxidant, enantioselective couplings (44-96% ee) could be achieved for a range of 3-substituted 2-naphthols including the ester, ketone, phosphonyl, and sulfonyl derivatives. The relationship between the substitution of the naphthalene starting materials and reactivity/selectivity is determined by several factors which act in concert: (1) the effect of substituents on the oxidation potential of the substrate, (2) the ability of the substrate to participate in a chelated copper complex which depends on (a) the inherent coordinating ability of the 3-substituent and (b) substituent steric interactions that affect chelation between the 2-hydroxyl and 3-substituent, (3) the effect of substituents on dissociation of the product from the copper catalyst.     

DMAP-catalyzed four-component one-pot synthesis of highly functionalized spirooxindole-1,4-dihydropyridines derivatives in aqueous ethanol

An efficient, clean, and environmental friendly ‘one-pot’ four-component reaction was developed for assembling a novel type of spirooxindole derivatives containing dihydropyridine and pyrrolidinone. The reaction could be easily performed in aqueous ethanol with 4-DMAP as catalyst in good yields. The high efficiency and the simple and mild condition of the reaction, in addition with its avoidance of time-consuming, costly syntheses, and tedious workup, endowed the reaction with application significance. A series of spirooxindole derivatives were therefore prepared in excellent yields by using this ‘one-pot’ four-component reaction method.     

Cyclization reactions of N-acryloyl-2-aminobenzaldehyde derivatives: formal total synthesis of martinellic acid

N-Alkyl acryloylamides derived from o-aminobenzaldehyde derivatives react with N-alkyl glycine derivatives to provide cis-fused pyrrole[3,2-c]quinolones in moderate yield and high diastereoselectivity. These same substrates engage in a tandem Michael-Mannich pathway on treatment with a secondary amine, providing corresponding quinolone derivatives. The elaboration of a pyrroloquinolone derivative via addition of an in situ generated functionalized copper acetylide to an in situ generated iminium ion provided the C2-substituted derivative. Global deprotection and reduction of the alkyne afford the tricyclic triamine core (as the HCl salt) found in martinellic acid.     

Asymmetric Michael addition reactions catalyzed by a novel upper-rim functionalized calix[4]squaramide organocatalyst

A novel upper-rim functionalized calix[4]squaramide organocatalyst bearing bis-squaramide and cyclohexanediamine scaffolds was designed and prepared to catalyse a serial of asymmetric Michael addition of 1,3-dicarbonyl compounds to α,β-unsaturated carbonyl compounds in high yields (up to 99 %) and good to excellent enantiomeric excesses (up to 99% ee). The comparative experiments indicated that the cooperative effect between calixarenes cavitives and chiral catalytic centers on this calix[4]squaramide catalyst could promote these reactions. Moreover, this strategy also provides valuable and easy access to chiral chromene, naphthoquinone and acetylacetone derivatives, which are important skeletons in biological and pharmaceutical compounds.