Novel Metal-Free Synthesis of 3-Substituted Isocoumarins and Evaluation of Their Fluorescence Properties for Potential Applications.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.

Synthesis of Luminescent Indolo[2,1-b]quinazolin-6(12H)-ones via a Sequential Ugi/Iodine-Promoted Cyclization/Staudinger/Aza-Wittig Reaction.

A new efficient synthesis of indolo[2,1-b]quinazolin-6(12H)-ones via a sequential Ugi/iodine-promoted cyclization/Staudinger/aza-Wittig reaction was developed. The acid catalyzed three-component reactions of 2-azidobenzaldehydes, 2-[2-(trimethylsilyl)ethynyl]benzenamines (or o-aminoacetophenones), and isocyanides gave Ugi-3CR intermediates, which reacted subsequently with I2/DMSO and triphenylphosphine to produce indolo[2,1-b]quinazolin-6(12H)-ones in good overall yields. The obtained indolo[2,1-b]quinazolin-6(12H)-ones were all colored in bright red or orange. Their luminescent property was studied preliminarily and some of them showed high molar absorption coefficients, strong fluorescence emission intensity, and good absolute light quantum yields.

Stereoselective Synthesis of 12-Tetrazolyl Substituted (E)-5H-Quinazolino[3,2-a]quinazolines via Sequential Ugi-Azide/Staudinger/aza-Wittig/Addition/Ag(I)-Catalyzed Cyclization.

A new efficient and stereoselective synthesis of 12-tetrazolyl substituted (E)-5H-quinazolino[3,2-a]quinazolines via sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag(I)-catalyzed cyclization was developed. The four-component reactions of 2-azidobenzaldehyde, 2-(alkynyl)benzenamine, isocyanide, and trimethylsilyl azide gave Ugi-azide intermediates, which were subsequently treated with triphenylphosphine and isocyanate to produce 12-tetrazolyl substituted (E)-5H-quinazolino[3,2-a]quinazolines in the presence of Ag(I) catalyst and K2CO3.

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence.

A new efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reaction has been developed. The three-component Passerini reactions of 2-azidobenzaldehydes 1, benzoic acid (2), and isocyanides 3 produced the azide intermediates 4, which were treated sequentially with triphenylphosphine, isocyanates (or CS2), and secondary amines to give polysubstituted 3,4-dihydroquinazolines 8 and 4H-3,1-benzothiazines 11 in good overall yields through consecutive Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reactions.

Four-Component Synthesis of Polysubstituted Pyrazin-2(1H)-ones through a Ugi/Staudinger/Aza-Wittig/Isomerization Sequence.

A new efficient synthesis of polysubstituted pyrazin-2(1H)-ones via the sequential Ugi/Staudinger/aza-Wittig/isomerization reaction has been developed. The four-component Ugi reactions of arylglyoxals 1, primary amines 2, α-azidovinyl acids 3, and isocyanides 4 produced the azides 5, which were treated with triphenylphosphine to give pyrazin-2(1H)-ones 6 in good yields through domino Staudinger/aza-Wittig/isomerization reactions.

Isocyano(triphenylphosphoranylidene)acetates: Key to the One-Pot Synthesis of Oxazolo[4,5-c]quinoline Derivatives via a Sequential Ugi/Wittig/aza-Wittig Cyclization Process.

A one-pot novel strategy is described for the construction of various oxazolo[4,5-c]quinoline derivatives starting from the isocyano(triphenylphosphoranylidene)acetates, aldehydes, amines, and 2-azidobenzoic acids. The reactions generated the target products directly in moderate to good yields via a sequential Ugi/Wittig/aza-Wittig cyclization process. The salient features of the method are that all three groups of the multifunctional isocyanides were involved in the reaction with broad substituent scopes and mild reaction conditions, making the protocol a useful contribution to the synthesis of oxazolo[4,5-c]quinoline heterocycles.

One-Pot-Three-Component Synthesis of 2-(1,2,3,4-Tetrahydroisoquinolin-1-yl)oxazoles via DEAD-Promoted Oxidative Ugi/Wittig Reaction.

A new efficient DEAD-promoted oxidative Ugi/Wittig reaction for the preparation of 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)oxazoles has been developed. The one-pot reactions of odorless isocyano(triphenylphosphoranylidene)acetates, carboxylic acids, and N-aryl-1,2,3,4-tetrahydroisoquinolines produced polysubstituted 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)oxazoles directly in good yields in the presence of DEAD oxidant.

Synthesis of 2-Tetrazolyl-Substituted 3-Acylpyrroles via a Sequential Ugi-Azide/Ag-Catalyzed Oxidative Cycloisomerization Reaction.

A new efficient Ag-catalyed cascade cycloisomerization/aerobic oxidation reaction of a Ugi-azide adduct for the preparation of 3-acylpyrroles using molecular oxygen as the terminal oxidant has been developed. A series of 2-tetrazolyl-substituted 3-acylpyrroles were obtained in 62-89% yields from readily available enynals 1, primary amines 2, isocyanides 3, and trimethylsilyl azide 4 in the presence of a catalytic amount of AgNO3 and DMAP under an O2 atmosphere.

Synthesis of iminoisoindolinones via a cascade of the three-component Ugi reaction, palladium catalyzed isocyanide insertion, hydroxylation and an unexpected rearrangement reaction.

A robust ligand-free palladium-catalyzed cascade reaction for the synthesis of diversely substituted iminoisoindolinones has been developed. The cascade reaction involves isocyanide insertion into Ugi-3CR adducts, accompanied by unexpected hydroxylation and rearrangement.

One-Pot Synthesis of Polysubstituted Imidazoles via Sequential Staudinger/aza-Wittig/Ag(I)-Catalyzed Cyclization/Isomerization.

A new one-pot preparation of polysubstituted imidazoles by a Staudinger/aza-Wittig/Ag(I)-catalyzed cyclization/isomerization has been developed. The easily accessible propargylazide derivatives reacted with triphenylphosphine, isocyanates, and amines sequentially to produce the fully substituted imidazoles in good overall yields in the presence of catalytic amount of AgNO3/DMAP.

One-Pot Synthesis of Indoles by a Sequential Ugi-3CR/Wittig Reaction Starting from Odorless Isocyanide-Substituted Phosphonium Salts.

A new one-pot preparation of indoles by a Ugi-3CR/Wittig sequence has been developed. The reaction of odorless isocyanide-substituted phosphonium salt 5, aldehyde 6, and amine 7 produced the indoles 9 in 45-82% yields via a sequential Ugi-3CR/Wittig reaction in the presence of H3PO4 and solid K2CO3, respectively.

One-Pot Synthesis of Multisubstituted Benzimidazoles via Sequential Ugi and Catalytic Aza-Wittig Reaction Starting from 2-Aminobenzoyl Azides.

A simple and one-pot synthesis of multisubstituted benzimidazoles by a Ugi 4CC/catalytic aza-Wittig sequence was developed. The reaction of 2-aminobenzoyl azide 2, aldehyde 3, acid 4, and isocyanide 5 produced the benzimidazoles 8 in moderate to good yields via a sequential Ugi condensation and catalytic aza-Wittig in the presence of a catalytic amount of phospholene oxide.

One-pot synthesis of 1H-isochromenes and 1,2-dihydroisoquinolines by a sequential isocyanide-based multicomponent/Wittig reaction.

A one-pot synthesis of 1H-isochromenes and 1,2-dihydroisoquinolines by a I-MCR/Wittig sequence was developed. The reaction of phosphonium salt , an acid, an amine (or without), and an isocyanide gave the 1H-isochromenes or 1,2-dihydroisoquinolines in good yields by a sequential Passerini or Ugi condensation and an intramolecular Wittig reaction in the presence of K2CO3.

Unexpected Synthesis of 5,6-Dihydropyridin-2(1H)-ones by a Domino Ugi/Aldol/Hydrolysis Reaction Starting from Baylis-Hillman Phosphonium Salts.

A one-pot synthetic approach to 5,6-dihydropyridin-2(1H)-ones has been developed using a domino process involving Ugi, aldol, and hydrolysis reactions, starting with Baylis-Hillman phosphonium salts, primary amines, isocyanides, and arylglyoxals.

Synthesis of 2,3-Dihydro-1H-2-benzazepin-1-ones and 3H-2-Benzoxepin-1-ones by Isocyanide-Based Multicomponent Reaction/Wittig Sequence Starting from Phosphonium Salt Precursors.

A one-pot synthesis of multisubstituted 2,3-dihydro-1H-2-benzazepin-1-ones and 3H-2-benzoxepin-1-ones by an I-MCR/Wittig sequence was developed. The reaction of phosphonium salt 3, arylglyoxals 4, amine 5 (or without), and isocyanide 6 produced the 2,3-dihydro-1H-2-benzazepin-1-ones 8 or 3H-2-benzoxepin-1-ones 10 in good yields via a sequential Ugi or Passerini condensation and intramolecular Wittig reaction in the presence of NEt3.

Design and syntheses of novel N'-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide as inhibitors of cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase.

Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (Cy-FBP/SBPase) is an important target enzyme for finding inhibitors to solve harmful algal bloom (HAB). In this study, as potential inhibitors of Cy-FBP/SBPase, a series of novel chromone-connecting benzohydrazone compounds (Novel N'-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide) were designed and synthesized. Their inhibitory activities against Cy-FBP/SBPase were further examined in vitro. Some of these compounds, such as f6-f8, f11, f12 and f16, exhibit higher inhibitory activities (IC50=11.2-16.1 µM), especially, the compound f7 was identified as the most potent inhibitor with IC50 value of 11.2 µM. The probable binding-mode of compound f7 was further analyzed carefully by molecular docking methods. These results indicate that compound f7 could be used as a lead compound for further optimization and might have potential to be developed as a new algicide.

Synthesis, fungicidal activity, and sterol 14α-demethylase binding interaction of 2-azolyl-3,4-dihydroquinazolines on Penicillium digitatum.

A series of new 2-azolyl-3,4-dihydroquinazolines 6 was synthesized by direct cyclization of imidazole or 1,2,4-triazole with carbodiimides 4, which were obtained from aza-Wittig reaction of iminophosphorane 3 with isocyanate. The preliminary bioassay results demonstrated that most of the 2-imidazolyl-3,4-dihydroquinazolines 6a-6i exhibited good to significant fungicidal activity against Penicillium digitatum , whereas 2-triazolyl-3,4-dihydroquinazolines 6j-6t exhibited low fungicidal activity. Some of the 2-imidazolyl-3,4-dihydroquinazolines 6a-6i also exhibited strong binding interaction with the cytochrome P450-dependent sterol 14α-demethylase (CYP51). For example, compound 6e showed the best fungicidal activity against P. digitatum with IC(50) = 4.14 µg/mL and the best CYP51 binding activity with K(d) = 0.34 µg/mL, both superior to those of the agricultural fungicide triadimefon.

Unexpected synthesis of 2,4,5-trisubstituted oxazoles via a tandem aza-Wittig/Michael/isomerization reaction of vinyliminophosphorane.

2,4,5-Trisubstituted oxazoles 6 were unexpectedly prepared from a tandem reaction of vinyliminophosphorane 3 with various acyl chlorides in a one-pot fashion.

Synthesis of 1,2,4,5-tetrasubstituted imidazoles by a sequential aza-Wittig/Michael/isomerization reaction.

Carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aryl isocyanates, reacted with secondary amines in the presence of a catalytic amount of sodium alkoxide to give 1,2,4,5-tetrasubstituted imidazoles 7 in good yields. However, 4-acylimidazoles 11 were obtained, as phenols were used in the presence of a catalytic amount of potassium carbonate due to further air oxidation of the expected products 10.

Unexpected synthesis of indolo[1,2-c]quinazolines by a sequential Ugi 4CC-Staudinger-aza-Wittig-nucleophilic addition reaction.

A new sequential Ugi-Staudinger-aza-Wittig-nucleophilic addition reaction was developed to construct indolo[1,2-c]quinazoline derivatives, starting from the easily accessible 2-azidobenzaldehyde, carboxylic acid, 2-acylaniline and isocyanide. It is noteworthy that this is the first report of the cyclization of the Ugi adduct to give a dihydroindole ring system with two quaternary carbon centers, via the nucleophilic addition reaction of the methine group to the carbonyl group.