Microwave-assisted multicomponent reaction in water leading to highly regioselective formation of benzo[f]azulen-1-ones

Microwave-assisted three-component reaction has been established for the regioselective synthesis of benzo[f]azulen-1-ones. The reaction was performed in aqueous media under microwave irradiation by using readily available and inexpensive starting materials. A total of 38 examples were examined to show a broad substrate scope and good overall yields (70-89%). The present new synthesis shows attractive green chemistry characteristics, such as the use of water as reaction media, concise one-pot conditions, short reaction periods (7-24 min), easy work-up/purification, and reduced waste production without the use of any strong acids or metal promoters.     

Rapid formation of chemical complexity via a modified Biginelli reaction leading to dihydrofuran-2(3H)-one spiro-derivatives of triazolo[1,5-a]pyrimidine

The regio- and stereoselective, catalyst-free multicomponent synthesis of spiro-conjugated dihydrofuran-2(3H)-one/triazolo[1,5-a]pyrimidine derivatives in good to high yields via a Biginelli approach starting from ortho-substituted benzaldehydes, 3-amino-1,2,4-triazole and α-acetylbutyrolactone is reported. A plausible reaction mechanism for this transformation is discussed. The obtained heterocycles possess a drug-like conformationally restricted structure with defined stereochemistry and increased stability compared to other products obtained by this mode of the Biginelli reaction.     

An unexpected multicomponent reaction leading to 2-arylpyrrolo[2,3,4-kl]acridin-1(2H)-ones

An unexpected condensation profile was observed for the three-component reaction of 5,5-dimethyl-1,3-cyclohexadione (dimedone), various anilines, and isatin leading to the synthesis of novel 2-arylpyrrolo[2,3,4-kl]acridin-1(2H)-ones in the ionic liquid [HMIm]HSO₄. Regeneration of the enamine group after the initial condensation reaction associated with participation of the restored amine group in translactonization with the pyrrolidone ring are suggested as the main differentiating events being favored over addition of the second dimedone molecule, with respect to similar reported reactions.     

Synthesis of conjugated enynes by assembly of three components, ketones, chloromethyl p-tolyl sulfoxide, and acetylenes, with the magnesium carbenoid 1,2-CC insertion as the key reaction

The reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium acetylides gave adducts in moderate to good yields. Treatment of the adducts with Grignard reagents resulted in the formation of magnesium carbenoids by the sulfoxide-magnesium exchange reaction. 1,2-Carbon-carbon insertion (1,2-CC insertion) reaction of the generated magnesium carbenoids took place to afford conjugated enynes in good to high yields. This procedure provides a good method for the synthesis of multi-substituted conjugated enynes.     

Consecutive Rh(I)-catalyzed Alder-ene/Diels-Alder/Diels-Alder reaction sequence affording rapid entry to polycyclic compounds

Conversion of acyclic allenynes to polycyclic compounds using consecutive transition metal catalyzed carbon-carbon bond forming reactions in a single chemical operation is described. Reaction of an allenyne with a Rh(I) catalyst affords a cross-conjugated triene via a formal Alder-ene reaction. The triene then participates in a Rh(I)-catalyzed intramolecular [4+2] cycloaddition reaction to generate a new conjugated diene. An external dienophile is added to this diene which then undergoes a second [4+2] cycloaddition reaction to afford a complex polycyclic ring system. This reaction sequence demonstrates the synthetic potential of allenynes and cross conjugated trienes and highlights the rapid increases in molecular complexity that are possible by one-pot sequential transition metal catalyzed carbon-carbon bond forming reactions.     

Asymmetric synthesis of both enantiomers of esters and γ-lactones from optically active 1-chlorovinyl p-tolyl sulfoxides and lithium ester enolates with the formation of a tertiary or a quaternary carbon stereogenic center at the β-position

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides having two different substituents at the 2-position, which were synthesized from aldehydes or unsymmetrical ketones and (R)-(−)-chloromethyl p-tolyl sulfoxide in two or three steps, with the lithium enolate of tert-butyl acetate gave optically active adducts in 99% chiral induction from the sulfur stereogenic center. The adducts were converted to optically active esters, carboxylic acids, and γ-lactones, which have a tertiary or a quaternary carbon stereogenic center at the β-position. A synthesis of optically active spiro-lactones was realized starting from 2-cyclohexenone by this method.     

An efficient three-component reaction involving [3 + 1 + 1] furannulation leading to furanonaphthoquinones in water

An efficient and clean green synthesis of highly substituted linear naphtho[2,3-b]-furan-4,9-dione derivatives, starting from 2-hydroxy-1,4-naphthoquinone, alkyl isocyanides and a variety of aldehydes, is described. This new method provides the first example of an efficient regioselective synthetic method for the synthesis of linear naphtho[2,3-b]-furan-4,9-dione ring systems by formation of three bonds. This [3 + 1 + 1] furannulation strategy affords furanonaphthoquinones in moderate to high yields, using water as a cheap, non-toxic, environmentally friendly solvent, in a one-step reaction, without the need of complicated work-up procedures. Correspondence: Mohammad Bagher Teimouri, Petrochemical Department, Iran Polymer and Petrochemical Institute, P.O. Box 14965-115, Tehran, Iran.     

Kinetics of the reaction between [chloro(phenyl)arsanyl]acetic and chloroacetic acids

The reaction between [chloro(phenyl)arsanyl]acetic and chloroacetic acids proceeds in alkaline aqueous medium by the Sn2 mechanism and is accompanied by alkaline hydrolysis of chloroacetic acid. Mean rate constants and thermodynamic parameters of the reaction are evaluated.     

A novel synthesis of 2,4,4-trisubstituted 2-cyclopentenones by consecutive reaction of 1-chlorovinyl p-tolyl sulfoxides with acetonitrile and its homologues

1-Chlorovinyl p-tolyl sulfoxides were synthesized from several kinds of ketones and chloromethyl p-tolyl sulfoxide in three steps in high overall yields. Treatment of the 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium (lithium α-carbanion of acetonitrile) at low temperature gave the adducts in almost quantitative yields. The adducts were then treated with LDA followed by excess lithium α-carbanion of the homologues of acetonitrile to afford 3,5,5-trisubstituted cyclopentadienyl enaminonitriles, which were hydrolyzed and heated under acidic conditions to give 2,4,4-trisubstituted 2-cyclopentenones in good overall yields.     

Concise [4+3] cycloaddition reaction of pyrroles leading to tropinone derivatives

A concise [4+3] cycloaddition reaction of pyrroles with 2-(silyloxy)allyl cations has been developed. The oxyallyl cations stabilized with a methylthio group or geminal methyl groups were generated from the corresponding allylic alcohols under the influence of a Brönsted acid (Tf₂NH), respectively. The use of N-nosyl-protected pyrroles as the four-carbon unit was found to give tropinone derivatives in high yield.     

Improvements in the preparation and use of [tris(trimethylsilyl)methyl]lithium

Improvements in the preparation and use of [tris(trimethylsilyl)methyl]lithium are described.     

An asymmetric synthesis of carboxylic acid derivatives,including lactic acid and α-amino acid derivatives,from optically active 1-chlorovinyl p-tolyl sulfoxides and ester lithium enolates with creation of chirality at the α-position

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from symmetrical ketones or methyl formate and (R)-(−)-chloromethyl p-tolyl sulfoxide in three steps, with lithium enolate of carboxylic acid tert-butyl esters gave optically active adducts having a substituent (alkyl, alkoxy, or dibenzylamino group) at the α-position with high 1,4-chiral induction from the sulfur chiral center. The adducts were converted to optically active esters, lactic acid, and α-amino acid derivatives having a chiral center at the α-position. When this addition reaction was carried out with an ester enolate generated from excess carboxylic acid tert-butyl ester with LDA in the presence of HMPA, the diastereomer of the adduct was obtained. By using the two reaction conditions for the generation of the ester enolate, a new method for asymmetric synthesis of both enantiomers of carboxylic acid derivatives having a substituent at the α-position from the one chiral source, (R)-(−)-chloromethyl p-tolyl sulfoxide, was achieved.     

Diastereoselective [2+2+1] Hydrative Annulation of Phenol-Linked 1,6-Enynes with Acetylenes Through Rhodium Catalysis: A Rapid Access to Cyclopenta[b]benzofuranols

An unprecedented [2+2+1] hydrative annulation of 1,6-enynes with terminal alkynes is achieved using catalytic cationic Rh(I). Thus, a modular assembly of cyclopenta[b]benzofuranols with two consecutive quarternary stereocenters is achieved from readily available alkynes. The reaction is proposed to go through a sequence of 5-membered rhoda-cycle formation, regioselective acetylene insertion, 1,5 H-shift, substrate controlled stereoselective addition of water molecule followed by 1,2-rhodium migration gave contracted rhoda-cycle D and reductive elimination. Necessary control/labelling experiments were conducted to gain insight in to the mechanism.     

Synthesis of ferrocenyl pyrazoles by the reaction of (2-formyl-1-chlorovinyl)ferrocene with hydrazines

Synthesis of ferrocenyl-substituted pyrazoles via the reaction between (2-formyl-1-chlorovinyl)ferrocene and hydrazine derivatives is described. Depending upon the substitution pattern of hydrazine, the reaction affords 1-alkyl/aryl-5-ferrocenylpyrazoles and/or 1-alkyl/aryl-3-ferrocenylpyrazoles. The reaction appears to be general for a variety of hydrazine derivatives.     

A new synthesis of amides and γ-lactones based on the conjugate addition of lithium enolate of amides to 1-chlorovinyl p-tolyl sulfoxides

Reaction of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones or aldehydes, with lithium enolate of N,N-dimethylacetamide gave the adducts in good to quantitative yields. The adducts were converted to several kinds of amides in high overall yields. Treatment of the adducts with trifluoroacetic anhydride in the presence of NaI resulted in the formation of γ-tolylsulfanylated γ-lactones in high yields. The scope and limitations of this method and the mechanism of the reactions are also discussed. These procedures offer a new and effective method for the synthesis of amides and γ-lactones having substituents on the β-carbon from N,N-dimethylacetamide with carbon elongation.     

Rh‐Catalyzed [5+1] and [4+1] Cycloaddition Reactions of 1,4‐Enyne Esters with CO: A Shortcut to Functionalized Resorcinols and Cyclopentenones

We have developed novel Rh‐catalyzed [n+1]‐type cycloadditions of 1,4‐enyne esters, which involve an acyloxy migration as a key step. The efficient preparation of functionalized resorcinols, including biaryl derivatives, from readily available 1,4‐enyne esters and CO was achieved by Rh‐catalyzed [5+1] cycloaddition accompanied by 1,2‐acyloxy migration. When enyne esters had an internal alkyne moiety, the reaction proceeded by a [4+1]‐type cycloaddition involving 1,3‐acyloxy migration, leading to cyclopentenones.     

Stereoselective Syntheses and Biological Properties of (E)-α-(Methoxyimino)-2-[1-(aryloxy)methyl]-benzeneacetates

(E)-α-(Methoxyimino)-2-[1-(aryloxy)methyl]-benzeneacetates, the analogues of Kresoxim-methyl, were stereoselectively synthesized with the coupling reaction of 2-methylphenyldiazonium chloride and methyl 2-hydroxyiminoacetate in the presence of CuSO4/Na2SO3 as a key step, and it was first found that the coupling reaction could give the key intermediate material(E)- and(Z)-methyl 2-(hydroxyimino)-2-o-tolylacetate with a molar ratio of 14∶1. The(E)-configurations of all these compounds were assigned on the basis of their 2D-NOESY spectra of 1H NMR. The preliminary bioassays indicate that most of the compounds show an activity against a wide variety of fungi.     

Synthesis of aromatic polyethers by Scholl reaction. V. Synthesis and polymerization of 1,3-bis[4-(1-naphthoxy) benzoyl]benzene, 1,4-bis[4-(1-naphthoxy)benzoyl]benzene,bis[4-(1-naphthoxy)phenyl]methane, 1,3-bis[4-(1-naphthoxy) phenylmethyl]benzene,and 1,4-bis-[4-(1-naphthoxy)phenylmethyl]benzene

This article describes the synthesis and the cation-radical polymerization (Scholl reaction) of 1,3-bis[4-(1-naphthoxy) benzoyl] benzene ( 6 ) and 1,4-bis[4-(1-naphthoxy) benzoyl]- benzene ( 7 ) initiated by FeCI₃. This polymerization produced poly(ether ether ketone ketone)s (PEEKK) of number average molecular weight (M?_n) up to 5400 g/mol. The synthesis of bis[4-(1-naphthoxy) phenyl] methane ( 8 ), 1,3-bis[4-(1-napthoxy) phenylmethyl] benzene ( 9 ), and 1,4-bis[4-(1-naphthoxy) phenylmethyl] benzene ( 10 ) are also described. Polyethers of M?_n up to 15400 g/mol at a FeCl₃/monomer molar ratio of 2/1 were obtained. An increased polymerizability of the monomers 9 and 10 containing two CH₂ groups versus that of the corresponding monomers containing two carbonyl groups ( 6 and 7 ) was observed. This enhanced polymerizability was explained based on the increased nucleophilicity of monomers 9 and 10 .