Three-component synthesis of pyran-fused biscoumarins: an entry to pyridinone- and pyranone-fused coumarins.

A base-mediated, three-component synthesis of symmetric and unsymmetric pyran-fused biscoumarins via the coupling of 4-hydroxycoumarin with 4-chloro-3-formylcoumarin in ethanol is reported. This methodology is further extended to the construction of various indole/coumarin-substituted symmetric pyran-fused biscoumarins. The unsymmetric pyran-fused biscoumarin can react with amines and 4-hydroxycoumarins under basic and acidic conditions to afford pyridinone-fused coumarins and pyranone-fused coumarins, respectively. The mechanisms of their formation are proposed.

Structural tuning of ß-enamino diketones: exploration of solution and crystalline state photochromism.

A library of ß-enamino diketones was prepared via base-mediated, three-component reaction of 4-hydroxycoumarins with various aromatic/aliphatic amines and ß-nitrostyrenes under microwave irradiation conditions to investigate their photochemical properties. Among the prepared compounds, a thiophene derived ß-enamino diketone was found to be light-sensitive and to exhibit unique photochromic behavior, that is, positive photochromism in solution and negative photochromism in crystalline phase. In addition, this prepared photochromic compound was further covalently linked to a structure-related, piezochromic ß-enamino diketone moiety to explore its potential multi-stimuli responsive properties.

4-Chloro-3-nitrocoumarin as a precursor for synthesis of 2-arylchromeno[3,4-b]pyrrol-4(3H)-ones: a case of nitro group directed reductive coupling.

A series of 2-aryl substituted chromeno[3,4-b]pyrrol-4(3H)-ones were prepared in two steps by employing 4-chloro-3-nitrocoumarin as a precursor. The reaction involved the base-mediated reductive coupling of 4-chloro-3-nitrocoumarin with α-bromoacetophenone, followed by reductive intramolecular cyclization to afford the pyrrolocoumarin ring. When α-bromoacetophenone was replaced with α-cyanoacetophenone, (E)-4-(nitromethylene)-4H-chromen-2-amine was isolated as the major product. The molecular structures of the prepared compounds were characterized by X-ray crystallography and the mechanisms for their formation were proposed.

(4 + 3) Cycloaddition Reaction of Sulfonylphthalide with N,N'-Cyclic Azomethine Imines: Synthesis of Pyrimidinone-Fused Naphthoquinones.

A base-mediated [4 + 3] cycloaddition reaction of sulfonylphthalide with N,N'-cyclic azomethine imines to facilely synthesize novel pyrimidinone-fused naphthoquinones is described. The prepared compounds can be readily converted to isoquinoline-1,4-dione derivatives via alkaline methanolysis. Alternatively, the isoquinoline-1,4-dione can also be prepared by base-mediated one-pot three-component reaction of sulfonylphthalide with N,N'-cyclic azomethine imines in methanol.

Lewis Acid-Catalyzed 1,4-Addition and Annulation of 4-Hydroxy-coumarins with o-Hydroxyphenyl Propargyl Amines: Entry to Regio-Selective Synthesis of Furano[3,2-c]coumarins and Pyrano[3,2-c]coumarins.

A facile and regioselective Lewis acid-catalyzed cascade annulation of o-hydroxyphenyl propargyl amines with 4-hydroxycoumarin to afford furano[3,2-c]coumarin and pyrano[3,2-c]coumarin derivatives is reported. The reaction presumably proceeds by the conjugate addition of 4-hydroxycoumarin to the in situ-generated alkynyl o-quinone methide and is followed by intramolecular 5-exo-dig and 6-endo-dig annulation to form furano[3,2-c]coumarins and pyrano[3,2-c]coumarins, respectively. The prepared o-hydroxyl substituted pyrano[3,2-c]coumarins could be readily transformed into the corresponding coumarin-derived dioxabicycles by acid-mediated cyclization.

Intramolecular Diels-Alder Cycloaddition of Furan-Derived ß-Enamino Diketones: An Entry to Diastereoselective Synthesis of Polycyclic Pyrano[3,2-c]quinolin-5-one Derivatives.

A series of 1,3-cyclodiketone- and tetrahydroepoxyisoindole-fused ß-enamino dicarbonyl heterocycles were synthesized via a 1,4-diazabicyclo[2.2.2]octane-catalyzed, CH3NO2-mediated three-component reaction of 1,3-cyclodiketone, furfural, and allylamine in toluene. The target compounds were generated via the formation of ß-enamino diketone as a key intermediate, followed by intramolecular Diels-Alder cycloaddition. The prepared molecules bearing a quinoline-2,4-dione moiety could be further brominated with N-bromosuccinimide and diastereoselectively reduced by NaBH4 to afford pyrano[3,2-c]quinolin-5-one-derived heterocycles with six vicinal stereogenic centers.

Acid-catalyzed, regioselective [3 + 3] annulation of enaminones and α-substituted cinnamic acids: access to 3,4-dihydropyridones and 2-piperidinones.

An efficient strategy for the synthesis of structurally diverse 3,4-dihydropyridones and 2-piperidinones is reported. The former was prepared via acid-catalyzed Michael addition of enaminones to electron-deficient α-substituted cinnamic acids followed by lactamization, whereas the latter was synthesized by the same methodology except that cinnamic acids were replaced with coumarin 3-carboxylic acids. A unique regioselective reactivity of the enaminones toward different cinnamic acid derivatives is described.

Construction of 2-pyridones via oxidative cyclization of enamides: access to Pechmann dye derivatives.

An efficient protocol for the construction of structurally diverse 2-pyridone derivatives from imines and α,ß-unsaturated acid chlorides in a single operation is reported. The target compounds, including coumarin-8-oxoprotoberbine analogues and lamellarin G isomers, were prepared via thermal cyclization of the in situ generated enamides followed by thermal dehydrogenation. The cyclization of enamides was achieved by the introduction of an electron-withdrawing group on the α-carbon of acid chlorides. This methodology allows quick access to polycyclic Pechmann dyes via rare double oxidative cyclizations of dienamides under mild conditions.

Regiodivergent Synthesis of Bis(4-oxycoumarin)-based Dioxabicycles: Exploration of [4 + 4] (Heterocyclo)reversion/addition and 1,5-Hydrogen Shift Photochromism.

Two isomeric dioxabicyclic molecular skeletons were constructed by employing the concepts of divergent synthesis. A base-mediated and an acid-catalyzed pseudo-three-component reaction of two equivalents of 4-hydroxycoumarin and (Z)-3-chloro-3-phenylacrylaldehyde yielded the corresponding bis(4-oxycoumarin)-based 2,6- and 2,8-dioxabicycles, respectively. The prepared colorless 2,6-dioxabicycles turned red upon UV irradiation and underwent the reverse reaction when exposed to visible light. The photochromism was proposed to proceed via a sequential [4 + 4] (heterocyclo)addition/reversion and 1,5-hydrogen shift on the basis of photogenerated product-trapping experiments.

Application of Dimedone Enamines as Protecting Groups for Amines and Peptides.

A simple protocol for the protection of amines was realized through a base-catalyzed one-pot reaction of dimedone, ß-nitroalkene, and amine. Employing this strategy, a variety of amines/amino acids were protected in excellent yields. These acid/base stable protected amines can be deprotected by either ethylene diamine or hydrazine hydrate under mild conditions. The practical application of this orthogonal protecting group was demonstrated by the synthesis of cyclic peptide melanotan II via SPPS.

(2-Hy-droxy-phen-yl)(4,2':4',4''-terpyridin-6'-yl)methanone.

The title compound, C22H15N3O2, can be described as a ketone with a phenol substituent and a terpyridine ligand coordinated to the carbonyl group. The three six-membered rings of the terpyridine ligand are not coplanar. The dihedral angles between the mean planes of the central ring and the external pyridine ligands are 22.77 (9) and 26.77 (7)°. The central ring of the terpyridine ligand is also not coplanar with the o-hy-droxy phenyl ring, the dihedral angle being 39.72 (5)°. An intra-molecular O-H⋯O hydrogen bond occurs. The crystal structure of the title compound is consolidated by C-H⋯O and C-H⋯N hydrogen bonding inter-actions.

Synthesis of lamellarin R, lukianol A, lamellarin O and their analogues.

Three lamellarin alkaloids type III (lamellarin R, lukianol A and lamellarin O) were synthesized using the Barton-Zard reaction as a key step to construct the central pyrrole core. Some of their corresponding 4-benzoyl and 5-phenyl substituted pyrrole analogues were also prepared via an initial three-component reaction of glycine methyl ester, benzaldehyde, and chalcone to generate the pyrrolidine scaffold, and followed by DDQ oxidation and N-alkylation.

Elemental sulfur-promoted one-pot synthesis of 2-(2,2,2-trifluoroethyl)benzoxazoles and their derivatives.

A novel and direct strategy has been developed for the synthesis of 2-(2,2,2-trifluoroethyl)benzoxazoles by reaction of o-aminophenols and 2-bromo-3,3,3-trifluoropropene in the presence of elemental sulfur under metal-free conditions. The scope of this methodology was further extended to the synthesis of the trifluoroethylated benzothiazole and benzoimidazole derivatives. A plausible mechanism was proposed on the basis of isolation and characterization of a thioamide intermediate.

One-Pot Construction of 1-Phenylchromeno[3,4- b]pyrrol-4(3 H)-one: Application to Total Synthesis of Ningalin B and a Pyrrolocoumarin-Based Electrochromic Switch.

An efficient construction of 1-phenylchromeno[3,4- b]pyrrol-4(3 H)-one via coupling of 1-styrylpyrrolidine and 4-chloro-3-nitrocoumarin as a key step is reported. This reaction is further applied to the total synthesis of the natural product ningalin B in five linear steps with an overall yield of 41.5% and a pyrrolocoumarin-based electrochromic switch.

New design of highly sensitive AIE based fluorescent imidazole derivatives: Probing of sweat pores and anti-counterfeiting applications.

A novel aggregation induced emission based 2-(1-(3, 5-bis(trifluoromethyl)phenyl)-4,5-diphenyl-1H-imidazol-2-yl) phenol (4) (IMD) fluorescent tags (FTs) was designed by simple acid catalyzed five-member N-heterocyclic ring forming reaction process. Powder X-ray diffraction results showed mechanofluorochromic properties of IMD FTs are easily reversible under external force due to the decrease in crystallinity. These IMD FTs also exhibits strong cyan-blue luminescence in solid state with high quantum efficiency. Detailed investigation of latent fingerprints (LFPs) showed permanent, immutable and unique pores that are distributed on the ridges. The visualization of such sweat pores opens new avenue in the field of forensic science. Hence, the prepared IMD FTs exhibit excellent Lipophicity (LP) properties, which endorse its possible applications for the visualization of sweat pores present in the LFPs. The LFPs visualized by IMD FTs exhibit excellent efficiency, sensitivity, selectivity, low background hindrance and less toxicity. The obtained result evident that the prepared FT and followed technique opens possible applications for the visualization of LFPs on various porous/semi-porous/non-porous surfaces under UV 365 nm light.

Base-Dependent Divergent Annulation of 4-Chloro-3-formylcoumarin and Tetrahydroisoquinoline: Application to the Synthesis of Isolamellarins and Hydroxypyrrolones.

A series of pyrrolo[2,1- a]isoquinoline and coumarin-fused pentacyclic derivatives were synthesized via base-mediated divergent annulation of 4-chloro-3-formylcoumarin and tetrahydroisoquinoline as a key step. This method was then extended to the preparation of isolamellarins A and B (isolamellarin G trimethyl ether). When exposed to UV light, the pyrrolo[2,1- a]isoquinoline- and coumarin-fused pentacycles B were found to undergo aerobic oxidation to give the corresponding hydroxypyrrolones.

Multicomponent Synthesis of 1,3-Diketone-Linked N-Substituted Pyrroles, Pyrrolo[1,2- a]pyrazines, Pyrrolo[1,4]diazepines, and Pyrrolo[1,4]diazocines.

A new methodology is developed for the efficient synthesis of 1,3-diketone-linked N-substituted pyrroles, pyrrolo[1,2- a]pyrazines, pyrrolo[1,4]diazepines, and pyrrolo[1,4]diazocines in good yields via a Yb(OTf)3-catalyzed, nitromethane-mediated reaction of primary amine/diamine, furfural, and 1,3-diketone. Possible mechanisms for these multicomponent reactions are also proposed.

Structural tuning enables piezochromic and photochemical properties in N-aryl-ß-enaminones.

An efficient synthesis of N-aryl-ß-enaminones via Et3N-mediated, one-pot three-component reaction of 4-hydroxycoumarin/dimedone, ß-nitrostyrene/2-(2-nitrovinyl)thiophene, and arylamine in toluene under refluxed conditions is herein presented. Some prepared compounds were found to exhibit piezochromic properties. The XRD and SEM measurements of the piezochromic compound showed substantial crystal packing and morphology changes before and after grinding. Further, one prepared compound was found to be light-sensitive and can be converted to a furo[3,2-b]pyridin-2(4H)-one derivative upon UV irradiation. A plausible mechanism for this photochemical reaction was proposed.

One-Pot Synthesis of 3-Difluoromethyl Benzoxazole-2-thiones.

A one-pot strategy for the diversified synthesis of 3-difluoromethyl benzoxazole-2-thiones is reported. The reaction of 2-aminophenol, sodium chlorodifluoroacetate, and elemental sulfur in the presence of NaO t-Bu gives exclusively 3-difluoromethyl benzoxazole-2-thiones in good yield (up to 98%). The mechanism of this reaction presumably involves first cyclization of 2-aminophenols with thiocarbonyl fluoride, followed by N-difluoromethylation with difluorocarbene. The developed synthetic procedures are versatile, robust, and easily scalable for the synthesis of 3-difluoromethyl benzoxazole-2-thione derivatives, some of which have shown insecticidal activities.

Multicomponent synthesis of pyrano[2,3-c]coumarins.

A base-catalyzed, pseudo-four-component reaction of 4-hydroxycoumarin, two molecules of acetone, and amine towards the synthesis of pyrano[2,3-c]coumarins is reported. The mechanism of this multicomponent reaction is proposed. The reaction is further extended to the preparation of coumarin-substituted pyrano[2,3-c]coumarins by a base-catalyzed, pseudo four-component reaction of two molecules of 4-hydroxycoumarin and two molecules of acetone.