Convenient and efficient synthesis of functionalized unsymmetrical Z-alkenyl disulfanes

We developed a simple and efficient method for the synthesis of functionalized unsymmetrical Z-alkenyl disulfanes under mild conditions in moderate to good yields. The designed method is based on the reaction of Z-alkenyl thiotosylates with thiols in the presence of base. The developed method allows the preparation of unsymmetrical Z-alkenyl disulfanes bearing additional hydroxy, carboxy, or amino functionalities.

We developed a simple and efficient method for the synthesis of functionalized unsymmetrical Z-alkenyl disulfanes under mild conditions in moderate to good yields.     

Chan–Lam coupling reaction of sulfamoyl azides with arylboronic acids for synthesis of unsymmetrical N-arylsulfamides

An efficient method was developed for the synthesis of unsymmetrical N-arylsulfamides using sulfamoyl azides and arylboronic acids in the presence of 10 mol% of copper chloride as the catalyst. The reaction was facilitated in MeOH in an open flask at room temperature. Unlike the coupling of sulfamides and boronic acids, the use of sulfamoyl azides was found to be beneficial with respect to the yield and reaction time.

An efficient method was developed for the synthesis of unsymmetrical N-arylsulfamides using sulfamoyl azides and arylboronic acids in the presence of 10 mol% of copper chloride as the catalyst.     

Electrochemical sulfonylation of alkenes with sulfonyl hydrazides: a metal- and oxidant-free protocol for the synthesis of (E)-vinyl sulfones in water

An efficient electrochemical transformation of a variety of alkenes and sulfonyl hydrazides into vinyl sulfones with a catalytic amount of tetrabutylammonium iodide in water is reported. The reaction proceeds smoothly to afford vinyl sulfones with good selectivities and yields at room temperature under air in an undivided cell. Cyclic voltammograms and control experiments have been performed to provide preliminary insight into the reaction mechanism. The key features of this reaction include using pure water as solvent, transition metal- and oxidant-free conditions, and being easily scaled up to gram-scale synthesis.

An electrochemical sulfonylation of alkenes with sulfonyl hydrazides for the synthesis of (E)-vinyl sulfones in water is reported.     

Metal-free cascade synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones

A convenient metal-free synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones has been developed. In this procedure, various structural 2-aminopyrimidines, as well as 4,5-dihydroisoxazol-5-ols and pyrazoles were synthesized in moderate to excellent yields. A plausible mechanism was also proposed for the cascade reaction. This method represents an effective strategy towards the synthesis of unsymmetrical 2-aminopyrimidines.

A convenient metal-free synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones has been developed.     

One-step construction of unsymmetrical thioureas and oxazolidinethiones from amines and carbon disulfide via a cascade reaction sequence

A concise and versatile method for the construction of unsymmetrical thioureas and oxazolidinethiones from amines and carbon disulfide has been achieved in DMSO without addition of extra reagents. The present protocol is compatible with various secondary amines and primary amines, and suitable for intermolecular and intramolecular reactions. Diverse unsymmetrical thioureas and oxazolidinethiones were efficiently obtained in good to excellent yields via a cascade reaction sequence.

A versatile and efficient route for the preparation of unsymmetrical thioureas and oxazolidinethiones from amines and carbon disulfide has been achieved via a cascade reaction sequence.     

Palladium-catalyzed regioselective hydrosulfonylation of allenes with sulfinic acids

An atom-economic method of preparing allylic sulfones via hydrosulfonylation of allenes with sulfinic acids under Pd(0)-catalysis was reported. This process has a high degree of regio- and stereoselectivity, and provides the target product with a moderate to excellent yield. A wide range of nitrogen- or oxygen-containing linear E-allylic sulfones have been synthesized. With the support of experimental research, a possible mechanism was proposed.

A simple palladium-based catalytic system for hydrosulfonylation of allenamides was established. Various nitrogen-containing linear allylic sulfones can be generated in moderate to excellent yield with E-selectivity and 100% atom utilization.     

Visible-light-induced one-pot synthesis of sulfonic esters via multicomponent reaction of arylazo sulfones and alcohols

Sulfonic ester is a chemical structure common to many organic molecules, including biologically active compounds. Herein, a visible-light-induced synthetic method to prepare aryl sulfonic ester from arylazo sulfones was developed. In the present study, a one-pot reaction was carried out using arylazo sulfones, DABSO (DABCO·(SO₂)₂), and alcohols in the presence of CuI as a coupling catalyst and HCl as an additive to yield sulfonic esters via multicomponent reaction. This synthetic method afforded a wide range of sulfonic esters with high yields under mild conditions.

Facile and efficient one-pot synthesis of sulfonic esters has been achieved via visible-light-induced multicomponent reaction of arylazo sulfones, and alcohols in the presence of DABSO, CuI, and HCI.     

Highly selective cross-coupling reactions of 1,1-dibromoethylenes with alkynylaluminums for the synthesis of aryl substituted conjugated enediynes and unsymmetrical 1,3-diynes

A highly efficient method for the synthesis of aryl substituted conjugated enediynes and unsymmetrical 1,3-diynes via selective cross-coupling reactions of 1,1-dibromoethylenes with alkynylaluminums using the Pd(OAc)₂–DPPE and Pd₂(dba)₃–TFP complexes as catalysts, respectively, has been successfully developed. Though the alkyl substituted conjugated enediynes and unsymmetrical 1,3-diynes were not obtained, this case is also remarkable as the same starting materials could selectively produce either aryl substituted conjugated enediynes or unsymmetrical 1,3-diynes in moderate to excellent yields (up to 99%) in the different Pd–phosphine catalytic systems.

A highly efficient method for the synthesis of aryl substituted conjugated enediynes and unsymmetrical 1,3-diynes via selective cross-coupling reactions of 1,1-dibromoethylenes with alkynylaluminums has been successfully developed.     

Synthesis of 3,6-diaryl-1H-pyrazolo[3,4-b]pyridines via one-pot sequential Suzuki–Miyaura coupling

A practical synthesis of diarylpyrazolo[3,4-b]pyridine derivatives by a combination of chemoselective Suzuki–Miyaura cross-coupling reactions was developed. The sequential arylation strategy can be performed in a one-pot manner without much loss of efficiency when compared to the corresponding stepwise synthesis. These conditions are applicable to the coupling of a wide variety of aryl and heteroaryl-boronic acids with pyrazolo[3,4-b]pyridines with high selectivity of the C3 over the C6 position, thus enabling the rapid construction of a diverse array of medicinally important diarylpyrazolo[3,4-b]pyridines.

An efficient method to produce diarylpyrazolo[3,4-b]pyridines derivatives via combination of chemoselective Suzuki–Miyaura cross-coupling reactions has been developed.     

Three-component microwave-assisted synthesis of 3,5-disubstituted pyrazolo[3,4-d]pyrimidin-4-ones

A practical three-component method for the synthesis of pyrazolo[3,4-d]pyrimidin-4-ones was developed. The reaction was performed in a one-pot manner under controlled microwave irradiation using easily accessible methyl 5-aminopyrazole-4-carboxylates, trimethyl orthoformate, and primary amines. Under the optimized conditions, challenging substrates, such as N-1 unsubstituted 5-aminopyrazole-4-carboxylates with another substituted amino group in position 3, reacted selectively affording 5-substituted 3-arylamino-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones. The reaction tolerated a range of primary amines, including anilines. The advantages of the developed protocol include short reaction time, pot- and step-economy, and convenient chromatography-free product isolation. The structural features of representative products were explored by X-ray crystallography.

A practical three-component method for the synthesis of pyrazolo[3,4-d]pyrimidin-4-ones was developed.     

Pyridine-2-carboxylic acid as an effectual catalyst for rapid multi-component synthesis of pyrazolo[3,4-b]quinolinones

Green synthesis of pyrazolo[3,4-b]quinolinones was designed using bioproduct pyridine-2-carboxylic acid (P2CA) as a green and efficient catalyst. The multi-component reaction of aldehydes, 1,3-cyclodiones and 5-amino-1-phenyl-pyrazoles regioselectively produced pyrazolo[3,4-b]quinolinones in excellent yield (84–98%). Recyclization of the catalyst was also investigated. The electronic effect of the various substituents in aromatic rings indicated that the reaction proceeded through the carbocation intermediate. This newly designed protocol very quickly constructed products conventionally under milder conditions.

Green synthesis of pyrazolo[3,4-b]quinolinones was designed using bioproduct pyridine-2-carboxylic acid (P2CA) as a green and efficient catalyst.     

An efficient synthesis of 4,5-diaryl-3,4-dihydropyrimidin-2(1H)-one via a cesium carbonate-promoted direct condensation of 1-aryl-2-propanone with 1,1′-(arylmethylene)diurea

An efficient method for the synthesis of 4,5-diaryl-3,4-dihydropyrimidin-2(1H)-one by using 1,1′-(arylmethylene)diurea and 1-aryl-2-propanone as substrates was developed. The reactions proceeded efficiently in the presence of Cs₂CO₃ to give the desired products in moderate to good yields with wide substrate scope and good functional group tolerance, serving as an attractive alternative or complement to the previously reported methods for the facile assembly of biologically and pharmaceutically active 3,4-dihydropyrimidin-2(1H)-ones.

A Cs₂CO₃-promoted efficient method for the synthesis of 4,5-diaryl-3,4-dihydropyrimidin-2(1H)-one by using 1,1′-(arylmethylene)diurea and 1-aryl-2-propanone as substrates was developed.     

Visible-light-induced C(sp3)–H activation for a C–C bond forming reaction of 3,4-dihydroquinoxalin-2(1H)-one with nucleophiles using oxygen with a photoredox catalyst or under catalyst-free conditions

A convenient photocatalyzed oxidative coupling reaction of 4-alkyl-3,4-dihydroquinoxalin-2(1H)-one and its derivatives with a variety of nucleophiles was developed with a ruthenium photoredox catalyst and oxygen under a household compact fluorescent light. With a slower reaction rate, the cross coupling transformation can be achieved in the absence of an external photocatalyst with a similar isolated yield. An application to the synthesis of natural product cephalandole A was also demonstrated.

A convenient photocatalyzed coupling reaction of 4-alkyl-3,4-dihydroquinoxalin-2(1H)-one with a variety of nucleophiles was developed with a household compact fluorescent light. The synthesis of natural product cephalandole A was also demonstrated.     

Efficient and stereoselective one-pot synthesis of benzo[b]oxazolo[3,4-d][1,4]oxazin-1-ones

An efficient and mild one-pot convergent synthesis protocol has been developed for benzo[b]oxazolo[3,4-d][1,4]oxazin-1-one derivatives through the Mitsunobu reaction and sequential cyclization. Various tricyclic fused benzoxazinyl-oxazolidinones (20 examples) were obtained in good to excellent yields and high enantioselectivities with facile operation. Furthermore, four stereoisomers were afforded respectively in high ee values (>97.8%) via using different chiral 2,3-epoxy-4-trityloxybutanol. This methodology has been applied to the synthesis of key intermediates of drug candidates.

An efficient and mild one-pot convergent synthesis protocol has been developed for benzo[b]oxazolo[3,4-d][1,4]oxazin-1-one derivatives through the Mitsunobu reaction and sequential cyclization.     

CuI nanoparticle-catalyzed synthesis of tetracyclic benzo[e]benzo[4,5]imidazo[1,2-c][1,3]thiazin-6-imine heterocycles by SNAr-type C–S,C–N bond formation from isothiocyanatobenzenes and benzimidazoles

In this paper, a simple and practical synthesis of benzo[e]benzo[4,5]imidazo[1,2-c][1,3]thiazin-6-imine tetracyclic heterocycles via a CuI nanoparticle-catalyzed intramolecular C(sp²)–S coupling reaction is presented. This strategy provides a straightforward method for synthesizing analogs of the anti-HIV drug 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine (PD 404182). The reaction rate and yield were increased by employing CuI nanoparticles.

We proposed a practical synthesis of analogs of the anti-HIV drug 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine via a CuI nanoparticle-catalyzed intramolecular C(sp²)–S coupling reaction.     

Palladium nanoparticles as efficient catalyst for C–S bond formation reactions

The development of green, economical and sustainable chemical processes is one of the primary challenges in organic synthesis. Herein, we report an efficient and heterogeneous palladium-catalyzed sulfonylation of vinyl cyclic carbonates with sodium sulfinates via decarboxylative cross-coupling. Both aliphatic and aromatic sulfinate salts react with various vinyl cyclic carbonates to deliver the desired allylic sulfones featuring tri- and even tetrasubstituted olefin scaffolds in high yields with excellent selectivity. The process needs only 2 mol% of Pd₂(dba)₃ and the in situ formed palladium nano-particles are found to be the active catalyst.

Heterogenous catalysis: economical and sustainable synthesis of allylic sulfone featuring tri- and even tetrasubstituted olefin scaffold via decarboxylative cross-coupling from vinyl cyclic carbonates with sodium sulfinates using PdNPs as a catalyst.     

Substrate controlled,regioselective carbopalladation for the one-pot synthesis of C4-substituted tetrahydroisoquinoline analogues

6-Exo-trig cyclization reaction through regioselective carbopalladation was demonstrated with N-(2-halobenzyl)-N-allylamines to furnish the corresponding C4-substituted tetrahydroisoquinoline derivatives. The scope of the reaction was extended to the synthesis of C4-quaternary tetrahydroisoquinoline derivatives also. The nature of the substituent on the olefin moiety dictates the course of the carbopalladation sequence. Regioselective carbopalladation is substantiated by performing the reaction with unsymmetrical diallylated amine substrates.

6-Exo-trig cyclization reaction through regioselective carbopalladation was demonstrated with N-(2-halobenzyl)-N-allylamines to furnish the corresponding C4-substituted tetrahydroisoquinoline derivatives.     

Synthesis and fluorescent properties of boroisoquinolines,a new family of fluorophores

First representatives of a new family of isoquinolines, so called boroisoquinolines, were synthesized and characterized. The synthesis was based on the insertion of the difluoroboranyl group into the 1-methylidene-3,4-dihydroisoquinoline core. The optimization of the 2-difluoroboranyl-3,4-dihydroisoquinoline-1(2H)-ylidene core led to efficient fluorescence in a range of 400–600 nm with outstanding (>100 nm) Stokes shifts. The compounds might be suitable for reversible or irreversible labelling of proteins, particularly the cannabinoid receptor CB₂.

First representatives of a new family of isoquinolines, so called boroisoquinolines, were synthesized and characterized.     

Synthesis and antitumor effects of novel benzyl naphthyl sulfoxide/sulfone derivatives derived from Rigosertib

In this work, a series of novel benzyl naphthyl sulfoxides/sulfones derived from Rigosertib were designed and synthesized as potential antitumor agents. The in vitro cytotoxicity against four human cancer cell lines (HeLa, MCF-7, HepG2 and SCC-15) and two normal human cell lines (HUVEC and 293T) indicated that some of the sulfones and sulfoxides possessed potent antineoplastic activity that reached nanomolar levels and relatively low toxicity to normal cells. Among them, (2-methoxy-5-((naphthalen-2-ylsulfonyl)methyl)phenyl)glycine (15b) was found to be a promising antitumor drug candidate that could significantly inhibit tumor cell migration and induce tumor cell apoptosis via the p53-Bcl-2-Bax signaling pathway at nanomolar concentrations.

In this work, a series of novel benzyl naphthyl sulfoxides/sulfones derived from Rigosertib were designed and synthesized as potential antitumor agents.     

A multicomponent,facile and catalyst-free microwave-assisted protocol for the synthesis of pyrazolo-[3,4-b]-quinolines under green conditions

A facile, swift and ecofriendly microwave-assisted multi-component/one-pot protocol is designed for the synthesis of novel pyrazolo-[3,4-b]-quinolines at ambient temperature in aqueous ethanol as a reaction medium. The 18 novel pyrazolo-[3,4-b]-quinoline derivatives were synthesized by fusion of chosen aryl aldehyde, dimedone and 5-amino-3-methyl-1-phenylpyrazole in excellent yields (91–98%). All the molecular structures were confirmed by ¹H-NMR, ¹⁵N-NMR, ¹³C-NMR, and HRMS data analysis. Operational simplicity, easy handling, one-step simple workup procedure, mild reaction conditions, short reaction time (≤10 min), high selectivity and no by-product formation are the striking features of the protocol.

A facile, swift and ecofriendly microwave-assisted multi-component/one-pot protocol is designed for the synthesis of novel pyrazolo-[3,4-b]-quinolines at ambient temperature in aqueous ethanol as a reaction medium.