Pt(IV)-catalyzed cyclization of arene-alkyne substrates via C-H bond functionalization

We herein report that PtCl₄ has proven to be a hydroarylation catalyst with an efficiency and substrate scope superior to previously known methods. This catalyst demonstrated consistent performance with arene-yne substrates of diverse structural features, including propargyl ethers, propargylamines, and alkynoate esters, providing good to excellent yields of the 6-endo products (chromenes, dihydroquinolines, and coumarins). In contrast, Pt(II), Pd(II), and Ga(III) salts were shown to be sensitive to the substitution on the alkyne moiety. PtCl₄ is compatible with both terminal and disubstituted alkynes, as well as with various functionalities on the arene ring, including methyl, methoxyl, hydroxyl, protected amine, and halide.     

Acetyltrimethylsilane mediated synthesis of dihydrophenanthrenes

An easy and efficient synthesis of phenanthrene derivatives through base catalyzed ring transformation of 4-sec-amino-2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles with acetyltrimethylsilane is described in good yields. The advantage of this reaction is the direct transformation of 2-oxobenzo[h]chromene into phenanthrene via C-C insertion from acetyltrimethylsilane.     

A Facile Route to the Synthesis of New 2,3-Disubstituted Benzocoumarins

Triphenylphosphine catalyzes the reaction between 2-hydroxy-1-naphthaldehyde and π-deficient acetylenes to give the newly prepared benzo[f]chromenes. The mechanism for the formation of products is discussed.     

Asymmetric Michael Addition/Intramolecular Cyclization Catalyzed by Bifunctional Tertiary Amine–Squaramides: Construction of Chiral 2‐Amino‐4H‐chromene‐3‐Carbonitrile Derivatives

The efficient asymmetric Michael addition/intramolecular cyclization of malononitrile with dienones catalyzed by a chiral bifunctional tertiary amine–squaramide catalyst for the synthesis of chiral 2‐amino‐4H‐chromene‐3‐carbonitrile derivatives was developed. The corresponding products were obtained in good to excellent yields (up to 99 %) with excellent enantioselectivities (up to 98 % ee) for most of the bisarylidenecyclopentanones.     

Facile Synthesis of 2H-Benzo[h]Chromenes via an Arylamine-Catalyzed Mannich Cyclization Cascade Reaction

A simple arylamine-catalyzed Mannich-cyclization cascade reaction was developed for facile synthesis of substituted 2H-benzo[h]chromenes. The notable feature of the process included the efficient generation of ortho-quinone methides (o-QMs) catalyzed by a simple aniline. The mild reaction conditions allowed for a broad spectrum of 1- and 2-naphthols and trans-cinnamaldehydes to engage in the cascade sequence with high efficiency.     

Gold(I)-Catalyzed Intermolecular Formal [4+2] Cycloaddition of O-Aryl Ynol Ethers and Enol Ethers: Synthesis of Chromene Derivatives

Gold(I)-catalyzed formal [4+2] cycloaddition of O-aryl ynol ethers 1 and enol ethers 2 is described. This intermolecular reaction between two electron-rich unsaturated systems takes place, under mild conditions, in the presence of 5 mol% [IPrAu(CH₃CN)]SbF₆ as catalyst giving chromene derivatives with good yields. The cycloaddition is completely regio- and stereoselective, as well as versatile for both reactives. Silyl enol ethers can also react in the same way and under the same reaction conditions with quantitative yields. A plausible mechanism through a selective addition of the enol ether to the alkyne gold activated complex followed by an intramolecular aromatic electrophilic substitution is proposed. Several experimental results support the presence of a cationic oxonium intermediate prior to the aromatic substitution. The reaction represents a new entry to the chromene core.     

Brønsted Acid Catalyzed,Conjugate Addition of β‐Dicarbonyls to In Situ Generated ortho‐Quinone Methides—Enantioselective Synthesis of 4‐Aryl‐4H‐Chromenes

We describe herein a catalytic, enantioselective process for the synthesis of 4H‐chromenes which are important structural elements of many natural products and biologically active compounds. A sequence comprising a conjugate addition of β‐diketones to in situ generated ortho‐quinone methides followed by a cyclodehydration reaction furnished 4‐aryl‐4H‐chromenes in generally excellent yields and high optical purity. A BINOL‐based chiral phosphoric acid was employed as a Brønsted acid catalyst which converted ortho‐hydroxy benzhydryl alcohols into hydrogen‐bonded ortho‐quinone methides and effected the carbon–carbon bond‐forming event with high enantioselectivity.     

Synthesis,anticancer evaluation,and docking studies of some novel azo chromene derivatives

We have described a simple, convenient, and high-yielding one-pot synthesis of novel azo chromene derivatives via a three-component reaction of various azo aldehydes with dimedone and malononitrile using 10 mol% of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst and ethanol as solvent at reflux condition. All the synthesized compounds have been characterized using Fourier-transform infrared spectroscopy (FT-IR), ¹H NMR, ¹³C NMR, and HR-MS spectra and molecular docking was performed to explore new inhibitors of human placental aromatase cytochrome P450 and cyclooxygenase-2 enzymes. Of all the compounds docked, compound (E)-2-amino-4-(4,4-dimethyl-2,6-dioxocyclohexyl)-6-((3-methoxyphenyl)diazenyl-4H-chromene-3-carbonitrile ( 4o ) showed good binding affinity with the active site of human placental aromatase cytochrome P450 enzyme (PDB: 3EQM) with inhibition constant (Ki) 1.66 nM and compound 4o also showed good binding affinity with the active site of cyclooxygenase-2 enzyme (PDB: 6COX) with inhibition constant (Ki) 367.17 pM. In vitro anti-cancer activity studies against MCF-7 cells were also performed for compounds 4o , anastrozole and celecoxib. Compound 4o showed an effective cytotoxicity at 19.8 μg/ml compared to anastrozole and celecoxib (24.7 and 26.2 μg/ml).     

Hydroxypyridinechromene and Pyridinechalcone: Two Coupled Photochromic Systems

Substitution of the phenyl group in 2‐hydroxychalcones by a 4‐pyridine unit dramatically changes the network of chemical reactions of this compound: trans‐chalcone‐type ( Ct ), cis‐chalcone‐type ( Cc ), and a hemiketal (hydroxy‐4‐pyridinechromene) ( B ) and their protonated forms are formed, but the presence of a flavylium‐type cation could not be detected even at very acidic pH values. Moreover, whereas in 2‐phenyl‐2‐benzopyrylium compounds B and Cc are generally elusive species whose kinetic processes in aqueous solutions occur on the sub‐second timescale, in the present compound these species equilibrate on a timescale four orders of magnitude lower. Complete characterization of the equilibrium and kinetics of the reaction network could thus be achieved by ¹H NMR spectroscopy and UV/Vis spectrophotometry. The network of chemical reactions exhibits cis–trans photoisomerization, as well as photochromism between the hemiketal and the chalcone‐type species. The irradiation of Ct in MeOH/H₂O (1:1) at 365 nm produces B almost quantitatively through two consecutive photochemical reactions: Ct → Cc photoisomerization followed by Cc → B photo ring closure with a global quantum yield of 0.02. On the other hand, irradiation of B at 254 nm leads to a photostationary state composed by 80 % Ct and 20 % B , with a quantum yield of 0.21.     

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.