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A novel protocol was developed for the construction of highly functionalized 2-(diarylphosphoryl)-1,2-dihydropyridine derivatives (DAPDHPs) from 3-formylchromones (1), heterocyclic ketene aminals (HKAs, 2), and phosphine oxides (R2P(O)H, 3) via a novel, one-pot cascade reaction. Optimization of the reaction conditions determined that refluxing the mixture of the 3-formylchromones, HKAs, and various R2P(O)H in propylene carbonate (PC) in the presence of triethylamine as a base facilitated the highest yields of the DAPDHP products. This cascade reaction, which involved the cleavage of one C–O bond in the 3-formylchromone substrates and the formation of three new bonds (one C–C, one C–N, and one C–P bond), enabled the synthesis of a small library of DAPDHP products. The dearomatized DAPDHP products were formed by the regioselective nucleophilic addition of the R2P(O)H reagents to the intermediate pyridinium salts 8. This approach has several advantages such as the use of an environmentally-friendly solvent, simple and practical operation (with filtration and washing without column chromatography separation), good yields, and a product with potential biological activity.

A novel protocol for the construction of chromeno[2,3-b]pyrrol-4(1H)-ones (CMPOs) 3 from 3-formylchromones, and glycine derivatives via a cascade reaction was developed.

This strategy involved an unprecedented cascade reaction for the synthesis of CMPOs 3 and 3′via the cleavage of two bonds and the formation of three bonds in a single step.

A novel protocol for the synthesis of pyrido[2,3-b]indoles (α-carbolines, 3) from (E)-3-(2-oxo-2-phenylethylidene) indolin-2-one derivatives 1 and 1,1-enediamine (EDAM) 2a via an unexpected cascade reaction in ethanol was developed. Pyrido[2,3-b]indole derivatives 4 were obtained by the same reaction, albeit by stirring the mixture for a longer period of time (about 48 h). As a result, two kinds of functionalized α-carbolines 3 and 4 were synthesized by the facile reaction of the (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one derivatives and 2-(nitromethylene)imidazolidine under basic conditions (Cs2CO3) in ethanol. In addition, a diverse array of EDAM substrates (2b-2k) were tested in this reaction to afford the expected target compounds 5. This protocol is suitable for the combinatorial and parallel syntheses of natural-like products, including highly functionalized α-carbolines and pyrroles, especially 2-oxoindolin-3-yl pyrroles. This approach features several advantages, such as being a simple and practical operation (requiring only filtration and washing without column chromatography), furnishing excellent yields (72-98%), and producing diverse libraries of target compounds with potential biological activities.

A novel approach was developed for the synthesis of 5H-isochromeno [4,3-b]indolizin-5-ones (ICIDOs) 3 through a cascade reaction of 1,2,3-indantriones 1 with ethyl 2-(pyridine-2-yl)acetates 2. Various 5H-isochromeno [4,3-b]indolizin-5-ones were produced by heating of the mixture of 1,2,3-indantriones and ethyl 2-(pyridine-2-yl)acetates for approximately 8 ​h in an environmentally-friendly PEG200 solvent with catalyst of a few drops of acetic acid. This approach has several advantages such as the use of an environmentally-friendly solvent, simple and practical operation (with filtration and washing and no column chromatography separation), good yields (up to 91%), use of commercially available raw materials, diverse target compounds, and products with potential biological activity.

A novel protocol was developed for the construction of highly functionalized 5H-chromeno[4,3-d]pyrimidines (CMPDs) from 3-formylchromones, heterocyclic ketene aminals (HKAs), and amidine hydrochlorides via a novel cascade reaction involving ring-opening and 1,3-H shift reactions. As a result, a series of CMPDs was produced by exploitation of the cascade reaction, which involved the formation of three bonds and the cleavage of one bond through multiple reactions in one pot. This protocol can be used in combinatorial and parallel syntheses of various CMPD derivatives with the potential to exhibit biological activities against clinically relevant pharmacological targets and will be widely used for designing and synthesizing various novel chromene-containing heterocycles in the future.

This study aimed to develop a novel protocol for the synthesis of 2H-pyrrolo[1,2-a]imidazol-7(3H)-ones (PIDOs) from heterocyclic ketene aminals (HKAs) through an unprecedented cascade reaction by refluxing. Consequently, a series of PIDOs was produced through an amazing oxidative dimerization, followed by sequential cleavage of the C-N and C-C bonds in dimeric HKAs. This formation of PIDOs was accompanied by the formation and cleavage of many bonds. This method is suitable for the parallel construction of bicyclic pyrrolidone-like products.

A novel protocol for the construction of highly functionalized 2-(pyridin-3-yl)-chromeno[2,3-d]pyrimidines (PCPMDs) from 3-cyanochromone with 1,1-enediamines via an unprecedented cascade reaction has been developed by simply refluxing a mixture of 3-cyanochromone 1 and various types of 1,1-enediamines 2 under the catalysis of silver carbonate. As a result, a series of PCPMDs 3 were obtained through a novel cascade reaction involving an amazing electrocyclization mechanism of a cyano group with α,β-unsaturated nitriles. This reaction formation of PCPMDs was accompanied by the formation of four bonds and the cleavage of one bond in one step. This protocol can be used for the synthesis of various pyridin-3-yl-substituted complex pyrimidine derivatives, and it is suitable for combinatorial and parallel syntheses of PCPMD drugs or natural-like products.

A novel protocol for the synthesis of quinolizines (3) and quinolizinium salts (4) from chromone-3-carboxaldehydes 1 with ethyl 2-(pyridine-2-yl)acetate derivatives 2via an unprecedented cascade reaction in water was constructed. As a result, functionalized quinolizines (3) bearing a chromone skeleton were prepared by simple reflux of the mixture of chromone-3-carboxaldehydes with ethyl 2-(pyridine-2-yl)acetate derivatives in water. Quinolizinium salts (4) were also prepared in water under acidic conditions. The formation of quinolizinium salts was accompanied by the formation of two bonds and the cleavage of one bond in a single step. This protocol can be used in the synthesis of a wide variety of quinolizines and quinolizinium salts, and is suitable for combinatorial and parallel syntheses of quinolizine derivatives natural-like products. This approach has several advantages such as the use of an environmentally friendly solvent, simple and practical operation (with filtration and washing without column chromatography separation), excellent yields (83–96%), and formation of a product with potential biological activity.

A novel approach has been constructed for the synthesis of two types of 2-amino-4-coumarinyl-5-arylpyrroles (ACAPs, 5 and 6) through a cascade reaction and a metal-free catalyzed aerobic oxidation reaction of arylglyoxal monohydrates 1, 1,1-enediamines (EDAMs) 2 and 3, and 4-hydroxy-2H-chromen-2-ones 4 via multicomponent reactions to produce the target compounds with good to excellent yields. Specifically, hydroxyl-substituted 2-amino-4-coumarinyl-5-arylpyrroles, that is, 2-amino-4-coumarinyl-5-aryl-6-hydroxylpyrroles (ACAHPs) 6, were obtained by metal-free aerobic oxidation in 1,4-dioxane at simple reflux for approximately 10 h. As a result, ACAHPs 6 have been produced without metal catalysts or traditional oxidizing agents. This method represents a route to obtain the novel ACAPs in an environmentally friendly, concise, rapid, and practical manner with potential biological activity of the product.

A novel protocol for the preparation of functionalized 9-azabicyclo[3.3.1]nonane (ABCN) derivatives from 3-formylchromones, enaminones, and heterocyclic ketene aminals (HKAs) through an unprecedented cascade reaction has been developed by simply refluxing the mixture of the substrates 1-3. As a result, a series of ABCNs were produced through a very complex cascade reaction. This protocol can be used in the synthesis of ABCNs that are suitable for combinatorial and parallel syntheses of ABCN natural-like products in a one-pot reaction.

A novel protocol for the construction of highly functionalized bipyrimidine derivatives 4 and 5 from 3-formyl-chromones, ethyl 2-(pyridine-2-yl)acetate derivatives, and amidine hydrochlorides via an interesting and considerably complex multi-component cascade reaction was developed. The cascade reaction was manifested by refluxing a mixture of the three substrates in acetonitrile or DMF along with Cs2CO3. A series of 4,5-dihydro-[4,5'-bipyrimidin]-6(1H)-ones (DBPMOs) 4 was constructed regioselectively in suitable to excellent yields. Moreover, intermediates 4 then underwent a novel, metal- and oxidant-free cascade reaction to produce a series of [4,5'-bipyrimidin]-6(1H)-ones (BPMOs) 5. The formation of the bipyrimidine derivatives 4-5 was enabled by the formation of five bonds and the cleavage of one bond in one pot. This protocol can be used in the synthesis of functionalized bipyrimidine derivatives via a multi-component one-pot cascade reaction rather than multi-step reactions, which is suitable for both combinatorial and parallel syntheses of bipyrimidine derivatives.

A novel protocol for the synthesis of pyrido[2,3

This study aimed to develop a novel protocol for the synthesis of 2

A novel approach has been developed for the synthesis of three kinds of highly functionalized 2-aminopyridine derivatives (APDs) through a three-component reaction of 1,1-enediamines (EDAMs) 1, N,N-dimethylformamide dimethyl acetal (DMF-DMA) 2, and 1,3-dicarbonyl compounds 3–5 via a base-promoted cascade reaction, producing the desired products in good to excellent yields. This method represents a route to obtain a novel class of APDs in a concise, rapid, and practical manner. This approach is particularly attractive because of the following features: low cost, mild temperature, atom economy, high yields, and potential biological activity of the product.

An efficient and concise one-pot procedure was developed for the synthesis of two kinds of fluorinated 2-aminopyridine compounds, 4 and 5, based on the reactions of different types of 1,1-enediamines (EDAMs), 1, with a variety of benzaldehyde derivatives, 2, and 1,3-dicarbonyl compounds, 3, involving the Knoevenagel, Michael and cyclization reactions under heating. This protocol is especially suitable for efficient and rapid parallel synthesis of fluorinated 2-aminopyridine compounds with pharmacological activity. The usefulness of this environmentally benign, mild, and multicomponent one-pot reaction procedure was demonstrated by easily synthesizing two kinds of fluorinated 2-aminopyridine libraries.

A novel protocol for the construction of functionalized (Z)-3-(1(-arylamino)-2-oxoarylidene)indolin-2-ones (AOIDOs) from isatins 1 with nitro-substituted enamines 2via an unprecedented cascade reaction catalyzed by sulfamic acid is developed. The AOIDOs are prepared by simply refluxing a mixture of isatins with a wide variety of nitro-substituted enamines. Interestingly, the AOIDOs 3 were formed through the novel cascade reaction involving a unique cleavage of two C–N bonds of the nitro-substituted enamines. Overall, the novel reaction is accomplished by the formation of three new bonds and the cleavage of two C–N bonds in a single step. This protocol can be used in the synthesis of a wide variety of AOIDOs and is suitable for combinatorial and parallel syntheses of natural-like AOIDO products.

A novel class of 5H-[1,2,4]oxadiazolo[4,5-a]pyrimidine derivatives was prepared, characterized, and tested for its antibacterial and anticancer potential against thirteen strains and five human cancer cell lines. The synthetic method was optimized, and a proposed reaction mechanism was also presented. The compounds containing the 5-bromo-pyrimidine moiety exhibited moderate antibacterial potencies against Gram-positive strains. Furthermore, the newly prepared compounds displayed selectively antiproliferative activity against human cancer cell lines. These current results will help us to further optimize and develop new drug candidates for clinical studies as novel antibacterial or anticancer agents.

An efficient and concise protocol was developed for the synthesis of diverse morphan derivatives 5–7 by the Michael and aza-Michael reaction of different types of quinone monoketals 1 or quinone imine ketals 2 with enaminones or enamine esters 3 promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene in acetone at reflux. Notably, when cyclic enaminone 4 was used as a substrate in the aza-Michael and 1,2-addition reactions with quinone monoketals 1, they gave another novel morphan 8. This method is suitable for parallel synthesis of bridged ring compounds. As a result, highly diverse morphan derivatives were easily and efficiently prepared by the Michael/aza-Michael or aza-Michael/1,2-addition reactions.

A copper(II)-catalyzed protocol for the construction of aminothioalkenes has been achieved that is based on the reaction of enaminones with disulfides/thiophenols in the presence of tert-butyl hydroperoxide (TBHP) to give good to excellent yields. This study provides a new strategy for the formation of C(sp2)−S bonds via direct α-sulfenylation of C(sp2)−H bonds.

Aromatic sulfonyl halides are readily accessible from many sources. With newly synthesized N-arylphenothiazine catalysts, organocatalyzed photoredox polymerization has been developed with arylsulfonyl halides initiators using white or purple LEDs light sources. This method allows the preparation of poly(meth)acrylates and poly(meth)acrylamides possessing a broad scope of (hetero)aryl chain ends without metal-contamination concern. Investigations such as MALDI-TOF analysis, chain extension, and “ON/OFF” control experiments confirmed the fidelity of the polymer structure and reliability of this method. Moreover, this method facilitates the two-step preparation of brush polymers from polystyrene through an electrophilic aromatic substitution/organocatalyzed photopolymerization sequence.

A one-step protocol without transition-metal catalysts with simple post-treatment for the synthesis of 1,3-diazaheterocycle-fused [1,2-a]quinoline derivatives via the cascade reaction of 2-fluorobenzaldehyde (1) and heterocyclic ketene aminals (2) was developed. In the one-step cascade reaction, C═C and C–N bonds were constructed, and the targeted compound can be efficiently obtained by filtering without column chromatography. This protocol describes a valuable route to concisely and feasibly obtain 1,3-diazaheterocycle-fused [1,2-a]quinoline derivatives. The synthetic methodology is particularly attractive because of the following features: low-cost solvent, mild temperature, atom economy, high yield, and potential biological activity of the product.

A general and concise method was developed for the synthesis of highly functionalized morphans 3–4 by the Michael and hetero-Michael addition reaction of different types of quinone monoketals 1 and 1,1-enediamines 2 in ethanol or 1,4-dioxane at reflux. This method is suitable for the efficient parallel syntheses of N-containing heterocycles. A library of highly functional morphan derivatives was easily constructed using the Michael/hetero-Michael reaction.

A concise and efficient route for the synthesis of quinone methide substituted neonicotinoid derivatives (4–5) via the one-pot Cs2CO3-catalyzed 1,6-conjugate addition of N-benzyl nitro ketene amines (2) or 1,1-enediamines (3) with para-quinone methides (1) in acetone and an oxidation reaction using atmospheric oxygen has been developed. This protocol represents a route to obtain a novel class of quinone methide substituted neonicotinoid derivatives in a concise, rapid, and practical manner. This reaction is particularly attractive because of the following features: low-cost and biocompatible solvent, mild temperature, atomic economy, high yields, and potential biological activity of the product.

Two types of novel bicyclic compounds such as pyridinone 3 and 1,3-oxazinane derivatives 4 have been synthesised via the regioselective condensation reaction of heterocyclic ketene aminals (HKAs) with ethyl 2-cyano-3,3-bis(methylthio)-acrylate or 2-(bis(methyl-thio)methylene)-malononitrile in xylene at refluxing temperature. The bicyclic pyridinone compounds 3 can be efficiently obtained using catalyst-free conditions whereas 1,3-oxazinane derivatives 4 are obtained by adding Cs2CO3 under the same conditions. The reactions have the advantage of excellent yield, inexpensive raw materials and convenient final treatment.

Self-labeled inhibitors (SLIs) are promising for creating links, ranging from cancer therapy and metastatic pathways to mechanistic elucidation. In this study, a new category of “two-in-one” fluorescent xanthone inhibitors was developed for the systematic evaluation of anticancer activity and the selective imaging of cytoplasm in vitro. These xanthone inhibitors presented high fluorescent brightness, working over a wide pH range enabled by a “switchable reaction” of the heterocyclic backbone. The strength and nature of fluorescence were probed via spectroscopic methods and density functional theory calculations on the molecular level, respectively. Along with the potent anticancer activity, which was demonstrated using MTT and clonogenic assays with high fluorescent brightness in the cytoplasm, SLI 3fd could be established as a modeled self-monitoring drug in cancer therapy.

A novel method was developed for the construction of highly functionalized indole derivatives (3), including fluorinated indoles, via a site-selective, one-pot, two-step nucleophilic aromatic substitution reaction of o-difluorobenzene derivatives (1) with heterocyclic ketene aminals (HKAs) (2) promoted by two different bases (K2CO3 and Cs2CO3). A diverse library of indoles 3 was generated in good to excellent yields using a conventional base-mediated approach rather than metal catalysts. As a result, the highly functionalized indoles were easily obtained in an environmentally friendly, rapid, and practical manner, and the products have potential biological activity.

A concise and eco-friendly route for the synthesis of highly functionalized bicyclic pyridinium derivatives (3) via a one-pot reaction of chromone-3-carboxaldehydes (1) and N-benzyl nitro ketene aminals (NBNKAs) (2) under reflux in ethanol media has been developed. The targeted compound was efficiently obtained by filtration without further post-treatment. In the one-pot two step reaction, C—C and C═N bonds were constructed, while at the same time one C—O bond was cleaved. This protocol represents a valuable route to obtain highly functional bicyclic pyridinium derivatives in a concise, rapid, and practical manner. The reaction is particularly attractive due to features such as low cost, mild conditions, atom economy, high yield, using biocompatible solvent, and potential biological activity of the product.

The methods for the synthesis of two novel types of compounds, including pyridin-2-ones 3 and pyrimidin-4-ones 4 were developed. Pyridin-2-ones 3 were synthesised via the regioselective reaction of N,N′-disubstituted 1,1-ene diamines 1a–1w with mercaptals 2a–2c in acetonitrile promoted by Cs2CO3 under refluxing conditions. Fortunately, pyrimidin-4-ones 4 were obtained when the N-monosubstituted 1,1-ene diamines 1x–1b′, used as substrate, by accident, reacted with mercaptals 2 under similar conditions. As a result, two kinds of novel heterocycles were synthesised by this protocol. The reactions have some advantages, such as excellent yield, inexpensive raw materials and convenient final treatment. The antitumor bioactivity screening showed that certain compounds had potent antitumor activity. Especially, compounds 3r, which showed the most potent activity with IC50 values lower than 12.3 μmol L−1 against four human tumor cell lines, making it more active than cisplatin (DDP). In addition, a preliminary assessment of the structure–selectivity relationship of the compounds was also performed.

A efficient and concise one-pot procedure has been developed for the synthesis of highly functional morphan derivatives 3 based on diastereoselective double Michael addition reactions of various quinone monoketals 1 with a variety of heterocyclic ketene aminals (HKAs) 2 in the green solvent water at 60 °C. This protocol is especially suitable for efficient and rapid parallel syntheses of N-containing bridged heterocycles possessing pharmacological activities. As a result, a library of highly functional morphan derivatives was easily synthesized using this reported environmentally benign, mild, and catalyst-free one-pot reaction.

A concise and efficient one-pot synthesis of multi-halogen pyrazino[1,2-a]indole-1,8(2H,5aH)-dione (MHPID) derivatives by the reaction of an enamino ester with multi-halogen benzoquinone derivatives is described. MHPIDs 3a–3d were obtained with good yields (78–83%) by refluxing enamino esters 1a and 1b and tetrahalogen-1,4-benzoquinones 2a and 2b for 24 h without the use of catalysts. Compounds 3e–3p were also obtained with excellent yields (69–92%) via the reaction of the phenyl-substituted enamino esters 1c–1h with tetrahalogen-1,4-benzoquinones 2a and 2b in CH3CN catalyzed by Cs2CO3 . These two protocols are efficient and effective for the synthesis of MHPIDs.

A facile synthesis of highly functionized indanone fused multicyclic pyrrolines using the heterocyclic ketene aminal and ninhydrin is described. Derivative alkoxyl or amine substituted analogues were also directly achieved upon adding alcohols or amines as corresponding starting materials. The reaction conditions are environment friendly and have a good tolerance towards a variety of heterocyclic ketene aminals. A library including three series of molecularly diverse indanone fused pyrrolines with potential bioactivities was demonstrated to be rapidly constructed with good to excellent yields.

A general and concise method was developed for the synthesis of 2-amino-4,6-diarylpyridine derivatives 4–6 through the cascade reaction, which includes Michael addition, intramolecular cyclization, aromatization, and/or loss of HNO2, of different types of α,β-unsaturated ketones 1 and 1,1-enediamines 2 and 3 in 1,4-dioxane promoted by the base Cs2CO3 or piperidine. This method is suitable for the efficient parallel synthesis of pyridines. A library of highly functional 2-amino-4,6-diarylpyridine derivatives was easily constructed using the cascade reaction described in this study.