Metal-free and efficient approach to 4-thiocyanated 2H-chromenes via TFA-mediated cascade cyclization of 2-propynolphenols

A metal-free, Brønsted acid-mediated cascade cyclization of 2-propynolphenols for efficient synthesis of various 4-thiocyanated 2H-chromenes is developed by using KSCN as the thiocyanated source. This reaction was characterized by readily prepared starting materials, bearing good functional group tolerance and excellent yields. Moreover, the obtained 4-thiocyanated 2H-chromenes could be further derivated to potential bioactive and pharmaceutical molecules.     

Pseudo four-component reaction of salicylaldehydes and cyclic ketones with two molecules of malononitrile: A facile and efficient way to synthesize 4-[2-(dicyanomethylene)cyclic or heterocyclic]-2-amino-4H-chromenes

A new type of catalytic cascade pseudo four-component reaction has been found. The simple and facile pseudo four-component reaction of salicylaldehydes and cyclic or heterocyclic ketones with two molecules of malononitrile catalyzed by sodium acetate at ambient temperature results in the formation of 4-substituted 2-amino-4H-chromenes in 70–90% yields. Thus, a new simple and efficient ‘one-pot’ method to synthesize substituted 2-amino-4H-chromenes was found directly from such reasonable starting compounds as salicylaldehydes, cyclic or heterocyclic ketones and malononitrile.     

Multicomponent assembling of salicylaldehydes,malononitrile and cyanoacetamides: A simple and efficient approach to medicinally relevant 2-amino-4H-chromene scaffold

Sodium hydroxide catalyzed a new multicomponent reaction of salicylaldehydes, malononitrile and cyanoacetamides under ‘on-water’ conditions, which results in the facile and efficient formation of the corresponding substituted 2-amino-4H-chromenes in 80–95% yields. The convenient approach to the substituted 2-amino-4H-chromenes developed here — the promising small-molecule ligands for different biomedical applications with known spasmolitic, diuretic and antianaphylactic activities — is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a fast, efficient and environmentally benign ‘on-water’ synthetic concept for multicomponent reactions strategy.     

Potassium phthalimide promoted green multicomponent tandem synthesis of 2-amino-4H-chromenes and 6-amino-4H-pyran-3-carboxylates

A one-pot efficient, green, practical, and environmentally friendly multicomponent synthesis of 5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromenes, ethyl-6-amino-4-aryl-5-cyano-2-methyl-4H-pyran-3-carboxylates as well as 2-amino-4-aryl-7-hydroxy-4H-chromene-3-carbonitriles via tandem the Knoevenagel-cyclocondensation has been described in the presence of a green, low-cost, mild, efficient, and commercially available potassium phthalimide as the organocatalyst. This technique is a safe and ecofriendly approach to the synthesis of different 4H-chromens and 4H-pyrans that offers many merits including short reaction times, high yields, straightforward work-up, and no use of hazardous organic solvents.     

Facile and straightforward synthesis of the racemic version of 2-amino-4H-chromene-3-carbonitriles using K2HPO4 as an eco-friendly base

A simple and facile two-step synthetic route has been developed for the preparation of 2-amino-4H-chromenes via chalcone intermediate under an ambient condition, along with the crystallographic analysis of the racemic mixture so obtained. The crystal orientation can be very useful for generic drug development in future. The described non-hazardous optimized methodology also provides an alternative simple route to prepare functionalized 2-amino-4H-chromenes of biological interest.     

An ecofriendly approach to the synthesis of 2-imino- and 2-oxo-3-phenylsulfonyl-2H-chromenes

An efficient synthesis for 2-imino-3-phenylsulfonyl-2H-chromenes was developed from the Knoevenagel condensation of (phenylsulfonyl)acetonitrile and salicylaldehydes in aqueous sodium carbonate solution, at room temperature. Hydrolysis in aqueous HCl, at 80 °C, led to the formation of the corresponding 2-oxo-3-phenylsulfonyl-2H-chromenes, also isolated in excellent yields.     

Multicomponent assembling of salicylaldehydes,malononitrile, and 4-hydroxy-6-methyl-2H-pyran-2-one: A fast and efficient approach to medicinally relevant 2-amino-4H-chromene scaffold

A new multicomponent reaction (MCR) was found: a sodium acetate-catalyzed transformation of salicylaldehydes, malononitrile and 4-hydroxy-6-methyl-2H-pyran-2-one in ethanol results in the fast (30 min) and efficient formation of new 4-pyrano-substituted 2-amino-4H-chromenes in 86–96% yields. The same transformation initiated by grinding in mortar in the presence of sodium acetate or potassium fluoride results in a faster (15 min) formation of 4-pyrano-substituted 2-amino-4H-chromenes in 80–90% yields. This novel ‘one-pot’ process opens an effective and convenient way to pyrano-functionalized 2-amino-4H-chromene systems, which are promising compounds for different biomedical applications.     

An efficient regioselective reaction of indole with 2H-chromenes for the synthesis of new 4H-chromenes in environmentally benign media

An efficient regioselective, catalyst free, and green protocol has been developed for the synthesis of a novel class of 4H-chromene scaffolds at room temperature in ionic liquid. The method is general and applicable for a series of 2H-chromenes as well as indole derivatives.     

Diisopropyl azodicarboxylate mediated selective dehydrogenation of 2-amino-3-cyano 4H-chromenes

Selective dehydrogenation of 2-amino-3-cyano 4H-chromenes to the corresponding 2-iminochromenes mediated by diisopropyl azodicarboxylate under neutral conditions is reported. The dehydrogenation reaction is compatible with phenolic hydroxyl group and generates iminochromene in high yields. The methodology provides an easy access to coumarin and N-tosyl 2-amino-3-cyano-4-aryl 4H-chromenes.     

Organocatalytic asymmetric conjugate addition of malonates to 3-nitro-2H-chromenes

The conjugate addition of malonates to 3-nitro-2H-chromenes has been studied in the presence of a number of chiral organocatalysts. A bifunctional thiourea-tertiary amine was found to be an efficient catalyst for the reaction. Good yields and enantioselectivities were obtained for a variety of substituted 3-nitro-2H-chromenes. Diethyl malonate and diisopropyl malonate were applicable for the reaction with lower yields and similar enantioselectivities. 1,3-Diphenylpropane-1,3-dione also provided the corresponding product, however with a low yield and enantioselectivity.     

Synthesis of 2-amino-3-cyano-4H-chromen-4-ylphosphonates and 2-amino-4H-chromenes catalyzed by tetramethylguanidine

Synthesis of 2-amino-4H-chromen-4-ylphosphonates and 2-amino-4H-chromenes has been accomplished by the reaction of salicylaldehyde, malononitrile, dialkyl/diphenylphosphites catalyzed by 1,1,3,3-tetramethylguanidine (TMG) under neat conditions at room temperature. The applicability of catalytic TMG for the synthesis of 2-amino-4H-chromenes also has been described. The mild reaction conditions, simple work-up procedure, and use of TMG as an inexpensive catalyst provides an economical protocol for the preparation of important phosphorus-containing compounds.     

Efficient One-Pot Synthesis of 2,2-Dimethyl-2H-chromenes via Pd(II)-Catalyzed Coupling and SiO2-Promoted Condensation of o-Halophenols with 2-Methyl-3-buten-2-ol

An efficient synthesis of 2,2-dimethyl-2H-chromenes was accomplished by Pd(II)-catalyzed coupling and SiO₂-promoted condensation of o-halophenols with 2-methyl-3-buten-2-ol (1,1-dimethylallyl alcohol) in one pot. The method is very general and can be useful for the synthesis of some natural 2,2-dimethyl-2H-chromenes.     

Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes

A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac₂O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties.     

Nitroketene acetal chemistry: efficient synthesis of 2-amino-3-nitro-4H-chromenes

Base-catalyzed reaction of the nitroketene N,S-acetals and the ring substituted 2-hydroxybenzaldehydes afforded a combinatorial library of the 2-alkylamino-3-nitro-4-alkylsulfanyl 4H-chromenes in excellent yields. Nucleophilic displacement of the C4 alkylsulfanyl group with different thiols afforded 4H-chromenes with structural diversity.     

Enantioselective synthesis of 2-amino-5,6,7,8-tetrahydro-5-oxo-4H-chromene-3-carbonitriles using squaramide as the catalyst

The organocatalyzed enantioselective synthesis of a series of chiral 2-amino-5,6,7,8-tetrahydro-5-oxo-4H-chromene-3-carbonitriles was achieved using bifunctional squaramides as the catalysts. The tandem Michael addition–cyclization reaction of cyclohexane-1,3-diones and benzylidenemalononitriles gave the corresponding products in excellent yields (up to 99%) and moderate to good enantioselectivities (up to 83% ee). This investigation provides an efficient and useful process for the synthesis of chiral 2-amino-4H-chromenes.     

Organocatalytic cascade 1,6-conjugate addition/annulation/tautomerization of functionalized para-quinone methides: Access to chiral 2-amino-4-aryl-4H-chromenes

A novel organocatalytic cascade process initiated by 1,6-conjugated addition has been successfully developed. A range of pharmaceutically active 2-amino-4-aryl-4H-chromenes were readily obtained in high yields (88%-99%) and excellent enantiopurities (86%–99% ee).     

Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes

Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.     

Reactions of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes with thiophenols promoted by Lewis acid

A Lewis acid promoted nucleophilic substitution reaction between 2-(trifluoromethyl)-2-hydroxy-3-ethoxycarbonyl-2H-chromenes 1 and thiophenols affording thiophenyl substituted products, that is, 4-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-4H-chromene and 2-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-2H-chromene.     

An efficient and simple method for synthesis of 2,2-disubstituted-2H-chromenes by condensation of a phenol with a 1,1-disubstituted propargyl alcohol using BF3·Et2O as the catalyst

An efficient and simple method for the synthesis of 2,2-disubstituted-2H-chromenes by one-step cyclocondensation of a phenol with a variety of 1,1-disubstituted propargyl alcohols using BF₃·Et₂O as the catalyst is described.     

γ-Lactonizations of 2H-chromenes via cyclopropanation

A two-step synthesis of tetrahydro-2H-furochromenones from 2H-chromenes is reported. The reaction of a series of tert-butyl 2-diazoacetate derivatives with 2H-chromenes, catalyzed by Rh₂(OAc)₄, generated cyclopropane intermediates that rearranged to γ-lactones on treatment with Sn(OTf)₂.