Unusual O-conjugate addition reactions of β-ketoesters and 1,3-diketones to ethyl propynoate: applications to the synthesis of furans

Divinyl ethers were synthesized from 1,3-dicarbonyl compounds. Reactions of β-ketoesters and 1,3-diketones with ethyl propynoate in the presence of N-methylmorpholine produced unusual O-conjugate addition products in good yields. The divinyl ethers derived from 1,3-diketones were utilized for the synthesis of 2,3,5-trisubstituted furans under the standard radical cyclization conditions.     

Regioselectivity switch: gold(i)-catalyzed oxidative rearrangement of propargyl alcohols to 1,3-diketones

The gold(I)-catalyzed oxidative rearrangement of propargyl alcohols provides an efficient and selective route to 1,3-diketones under mild conditions. Pyridine-N-oxides were used as external oxidants with, different from related substrates, no alkylidenecycloalkanones or oxetan-3-ones formed as side-products.     

1,6-Conjugate addition of C-nucleophiles to p-quinone methide surrogate: Synthesis of diarylpropanes

1,6-Conjugate addition of various carbon nucleophiles to p-quinone methide surrogate is reported. The active methylene containing C-nucleophiles such as 1,3-diketones, diesters and ketoesters underwent two consecutive additions leading to bis-addition products, diarylpropanes. Whereas, nitroalkanes proceeded to contribute mono-addition products. Surprisingly, bromo analogue of p-quinone methide surrogate underwent halophilic dimerization reaction with excellent yield. The reported strategy provides an efficient synthesis of 1,3-diarylpropane derivatives bearing pharmacophoric ortho-methoxy phenol moiety under mild reaction conditions.     

Propargyl α-aryl-α-diazoacetates as robust reagents for the effective CH bond functionalization of 1,3-diketones via scandium catalysis

Propargyl α-aryl-α-diazoacetate a new class of reagent is developed for the effective CH bond functionalization of 1,3-diketones at room temperature. The combination of scandium triflate and propargyl α-aryl-α-diazoacetate proved to be efficient catalyst-reagent system for the controlled CH bond functionalization to afford 1,3-dicarbonyl alkylation. The protocol uses inexpensive Sc(OTf)₃ (5 mol%) and the reaction did not require the use of expensive catalysts or ligands and worked efficiently at room temperature. The practicality of the protocol has been demonstrated by the gram scale synthesis.     

Simultaneous Ring-Opened THF and insertion of diazoketone derived carbene into carbonyl O-H: Synthesis for β-keto enol ethers

A novel tandem synthesis of β-keto enol ethers was developed via the reaction of α-diazoketones, 1,3-diketones and THF catalyzed by cheap and available CuI under extremely simple conditions. During the course of the reaction, the ring-opened THF and diazocarbonyl derived carbene simultaneously inserted into O-H of 1,3-diketones.     

Convenient synthesis of ferrocenyl β-C-glycosydic spiropyrrolidines and pyrrolizidines through 1,3-dipolar cycloaddition reaction

An expedient method for the synthesis of ferrocene grafted β-C-glycosydic spiroheterocycles is reported through 1,3-dipolar cycloaddition reaction (1,3-DC reaction). The novel C-glycosyl dipolarophiles derived from d-glucose, d-mannose, and d-ribose underwent neat [3+2] cycloaddition reaction with the azomethine ylides generated from 1,2-diketones and secondary amino acids to give the corresponding β-C-glycosidic heterocycles in good yields. The electrochemical behavior of the cycloadducts is also described.     

FeCl3·6H2O-catalyzed selective conjugate reduction of alkylidene-β-keto esters and alkylidene-1,3-diketones

FeCl₃·6H₂O/triethylsilane composite catalyst system is successfully developed for the selective conjugate reduction of carbon-carbon double bond of Michael acceptor-alkylidene-β-keto esters and alkylidene-1,3-diketones under mild reaction conditions to afford the corresponding saturated β-keto esters and 1,3-diketones. The process involves the iron-catalyzed hydrosilylation, followed by in situ hydrolysis of silyl enol ether. The optimal reaction conditions include 20?mol% of FeCl₃·6H₂O and triethylsilane in dichloromethane at room temperature. A broad range of substrates undergoes the reduction in 1, 4-selective manner to afford the corresponding saturated compounds in excellent yields.     

Application of cyclic-1,3-diketones in domino and multicomponent reactions: facile route to highly functionalized chromeno[2,3-d]pyrimidinones and diazabenzo[b]fluorenones under solvent-free conditions

A facile and efficient protocol for the synthesis of chromeno[2,3-d]pyrimidinones and diazabenzo[b]fluorenones has been developed by one-pot three-component cyclocondensation of aldehydes, cyclic-1,3-diketones and 1,3-dimethylbarbituric acid in the presence of InCl₃ or P₂O₅ under solvent-free conditions.     

Cyclisation versus 1,1‐Carboboration: Reactions of B(C6F5)3 with Propargyl Amides

A series of propargyl amides were prepared and their reactions with the Lewis acidic compound B(C₆F₅)₃ were investigated. These reactions were shown to afford novel heterocycles under mild conditions. The reaction of a variety of N‐substituted propargyl amides with B(C₆F₅)₃ led to an intramolecular oxo‐boration cyclisation reaction, which afforded the 5‐alkylidene‐4,5‐dihydrooxazolium borate species. Secondary propargyl amides gave oxazoles in B(C₆F₅)₃ mediated (catalytic) cyclisation reactions. In the special case of disubstitution adjacent to the nitrogen atom, 1,1‐carboboration is favoured as a result of the increased steric hindrance (1,3‐allylic strain) in the 5‐alkylidene‐4,5‐dihydrooxazolium borate species.     

Tributylphosphine as a superior catalyst for the α-C-addition of 1,3-dicarbonyl compounds to electron-deficient alkynes

The present work describes an improved one pot access to α-(gem-difunctional) cinnamate esters and to conjugated 1,3-diketones exploiting the addition of 1,3-diketones, β-keto esters and malonates to alkynoates catalyzed by phosphines. Among the catalysts, nBu₃P was found as one of the most effective allowing the reaction to proceed in milder conditions and in a more general manner than with other phosphines.     

Free radical ring expansion and chain extension of 1,3-diketones

Free radical-promoted one carbon ring expansion and chain extension of 1,3-diketones including 1,3-diarylpropane-1,3-diones and 2-aroyl-3,4-dihydro-2H-naphalen-1-one to generate corresponding 1,4-diketones are described.     

Copper-catalyzed methylation of 1,3-diketones with tert-butyl peroxybenzoate

Copper-catalyzed radical methylation of 1,3-diketones with tert-butyl peroxybenzoate in air is described, providing a general pathway to α-methyl 1,3-diketones in moderate to good yields. This protocol has been scaled up to 50 g, and one of the synthesized products can be used in the synthesis of medicine, Rosuvastatin.     

Electronic effects in the reaction of 1,3-diaryl-1,3-diketones with hydrazinopyridines

The regioselectivity of the condensation of electronically unsymmetrical 1,3-diaryl-1,3-diketones with 2-hydrazinopyridine and 2,6-bis-hydrazinopyridine to form N-(2-pyridyl)-3,5-diarylpyrazoles was studied. Significant electronic effects on regioselectivities were observed, and regioselectivities were opposite to those exhibited by perfluoroalkyl/alkyl 1,3-diketones. The electronic effects correlate well to the difference between the Hammett σ⁺ coefficients of the para substituents on the aryl rings.     

Domino Knoevenagel-hetero-Diels-Alder reactions: a stereoselective synthesis of sugar-annulated furo[3,2-b] pyrano[4,3-d]pyran derivatives

The O-propargyl derivative of a sugar aldehyde derived from d-glucose undergoes smooth intramolecular domino Knoevenagel-hetero-Diels-Alder reactions with 1,3-diketones in the presence of CuI/Et₃N system in refluxing methanol to afford a novel class of carbohydrate analogues, furopyranopyrans in good yields. 1-Aryl-pyrazol-5-ones also undergo smooth coupling with O-propargyl tethered sugar aldehyde under similar conditions to furnish pyrazole-annulated furopyranopyrans. The stereochemistry of the products was assigned by various NMR experiments.     

Retro-Claisen condensation versus pyrrole formation in reactions of amines and 1,3-diketones

Cyclic amines and 1,3-diketones readily react under microwave irradiation to form ring-fused pyrroles in a single operation. A competing retro-Claisen pathway is efficiently suppressed by employing p-toluenesulfonic acid as an additive.     

Reactions of 2-Arylhydrazono-1,3-dicarbonyl Compounds with Ethylenediamine

2-Arylhydrazono-1,3-diketones react with ethylenediamine to give, depending on the substituents, dihydro-1,4-diazepine derivative or N,N'-ethylenebis(1,3-aminovinyl ketones). Treatment of the latter with nickel(II) or copper(II) acetate results in formation of the corresponding metal chelates. Nickel complexes of N,N'-ethylenebis(1,3-aminovinyl ketones) can also be synthesized from 2-arylhydrazono-1,3-diketones and ethylenediamine on a metal template. Reactions of 2-arylhydrazono-3-oxo esters with ethylenediamine yield N,N'-ethylenebis(3-alkyl-2-arylhydrazono-3-oxopropionamides). Ethyl 2-arylhydrazonoacetoacetate reacts with ethylenediamine under mild conditions, affording ethyl 2-p-tolylazo-3-[2-(2-p-tolylhydrazono-1,3-dioxobutylamino)ethylamino]-2-butenoate.     

NBS mediated protocol for the synthesis of N-bridged fused heterocycles in water

A facile and environmental friendly protocol for the synthesis of N-bridged fused bicyclic compounds such as imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[2,1-b]thiazole, from commercially available starting materials has been developed. The reaction proceeds via NBS mediated in situ formation of α-brominated intermediate of corresponding aromatic ketones, 1,3-diketones, β-keto esters, followed by trapping with suitable nucleophiles to provide these versatile imidazole fused bicyclic heterocycles in good yields under metal-free conditions.     

Solvent-free sonochemical one-pot three-component synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones

A rapid and efficient one-pot three-component protocol for the synthesis of 2H-indazolo[2,1-b]phthalazine-1,6,11-triones 4 and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones 6 has been developed by domino coupling of phthalhydrazide, 1,3-diketones, and aldehydes under solvent-free conditions at 80 °C as well as under solvent-free ultrasound irradiation at room temperature promoted by (S)-camphorsulfonic acid.     

Reactions of Bisazomethines of the Naphtalene Series with 1,3-Diketones

Bisazomethines prepared from aromatic dialdehydes and 2-naphthylamine were for the first time reacted with the following diketones: 1,3-cyclohexanedione, 5,5-dimethyl-1,3-cyclohexanedione, 5-phenyl-1,3-cyclohexanedione, indandione, and 2,2-dimethyl-1,3-dioxane-4,6-dione was studied. The reactions with 1,3-diketones of the cyclohexane series yield benzophenanthridine derivatives. The reactions with indandione, depending on conditions, give either bisarylideneindandiones or bisdihydrobenzo[f]indenoquinoline. As evidenced by the ^13C NMR and IR spectra, in the case of biphenyl-4,4'-dicarbaldehyde bis[N-(2-naphthyl)imine] and 2,2-dimethyl-1,3-dioxane-4,6-dione, 4,4'-bis(3-oxo-1,2,3,4-tetrahydrobenzo[f]quinolin-1-yl)biphenyl is formed.     

N-(α-Amidoalkyl)benzotriazole-mediated synthesis of β′-amido β-diketones: a general synthetic protocol for N-[β-(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl)alkyl] amides

Various β′-amido-β-diketones were first synthesized with N-(α-amidoalkyl)benzotriazole-mediated amidoalkylation of 1,3-diketones in moderate yields. These intermediates undergo rapid condensation with hydrazines to give the corresponding N-[β-(3,5-di and 1,3,5-trisubstituted pyrazol-4-yl)alkyl]amides.