A new laccase-catalyzed domino process and its application to the efficient synthesis of 2-aryl-1H-benzimidazoles

The laccase-catalyzed domino reaction of o-phenylenediamine and benzaldehydes with aerial oxygen as the oxidant exclusively yields 2-aryl-1H-benzimidazoles in good to very good yields. It is easy to perform under very mild reaction conditions.     

Laccase initiated oxidative domino reactions for the efficient synthesis of 3,4-dihydro-7,8-dihydroxy-2H-dibenzofuran-1-ones

Laccase initiated domino reactions of cyclohexane-1,3-diones with catechols using air as an oxidant afford 3,4-dihydro-7,8-dihydroxy-2H-dibenzofuran-1-ones with yields ranging from 70% to 97%.     

Synthesis of 5-thioxo-6H-imidazo[1,2-c]quinazolines and related compounds based on cyclocondensations of 2-isothiocyanatobenzonitrile (ITCB) with α-aminoketones

Pharmacologically relevant 5-thioxo-6H-imidazo[1,2-c]quinazolines and 5-oxo-6H-imidazo[1,2-c]quinazolines were prepared by sequential reactions of α-aminoketones with 2-isothiocyanatobenzonitrile (ITCB) and 2-isocyanatobenzonitrile (ICB), respectively. The functionalization of the thioxo moiety allowed the synthesis of 5-amino-6H-imidazo[1,2-c]quinazolines and of 1,2,4-triazolo[4,3-a]-imidazo[1,2-c]quinazolines.     

The first application of an imidazole o-quinodimethane in Diels-Alder reactions leading to the synthesis of benzimidazoles

An efficient procedure for the generation of the imidazole-4,5-quinodimethane intermediate 4 from 2-bromo-4,5-bis(bromomethyl)imidazole derivative 3 in boiling toluene in the presence of 18-crown-6 is described. o-Quinodimethane 4 was captured for the first time by several symmetrically and unsymmetrically substituted dienophiles to afford the corresponding Diels-Alder benzimidazole adducts.     

The first benzodiazepine o-quinodimethane: generation and Diels-Alder reactions

7,8-Bis(dibromomethyl)-3-bromo-2,4-diphenyl-3H-benzodiazepine 1 was used as a precursor for the benzodiazepine o-quinodimethane 2, which was trapped by in situ reactions with dienophiles.     

(1R,2R)-DPEN-derived triazolium salts for enantioselective oxodiene Diels-Alder reactions

Enantioselective oxodiene Diels-Alder reactions catalyzed by (1R,2R)-DPEN-derived triazolium salts were realized successfully. With 0.5 mol % of (1R,2R)-DPEN-derived triazolium salt C and 150 mol % of Et₃N, the reactions of various α-chloroaldehydes (α-bromoaldehyde) with substituted enones led to 3,4-dihydropyridinones and their derivatives in good yields, diastereoselectivities, and enantioselectivities (up to 97% ee).     

Diels-Alder reactions of masked o-benzoquinones with acrylonitrile

Regioselective Diels-Alder reactions of masked o-benzoquinones (MOBs) 2a-i derived from the corresponding 2-methoxyphenols 1a-i with acrylonitrile leading to highly functionalized bicyclo[2.2.2]octenone derivatives in high yields are described.     

Diels-Alder reactions of pyridinone o-quinodimethanes generated from substituted sulfolene[3,4-c]pyridin-4(1H)-ones

1-Benzyl-3-(bromomethyl)-2(1H)-pyrazinone was converted to [3,4-c] sulfolene pyridinone 8a and further (1- or 3-) substituted derivatives having a dienophilic side chain on the sulfolene ring. Thermolytic extrusion of sulfur dioxide from o-QDM precursor 8 led to generation of 3,4-dimethylene-2(1H)-pyrazinone 9, which was reacted in situ with various dienophiles. Thermolysis of the substituted precursors resulted in intramolecular cycloaddition of the corresponding o-QDM intermediates     

Chromone-3-carboxaldehydes in Diels-Alder reactions with indole-o-quinodimethane. Synthesis of tetrahydrochromeno[2,3-b]carbazoles

An efficient route to a new class of indole derivatives, tetrahydrochromeno[2,3-b]carbazoles, has been developed. The cycloaddition reactions of chromone-3-carboxaldehydes with indole-o-quinodimethane gave a diastereomeric mixture of Diels-Alder cycloadducts in good yields after in situ deformylation.     

Generation of 5,6-dimethylene-2(1H)-pyridinones from [3,4-b] sulfolene pyridinones and application in Diels-Alder reactions

2(1H)-Pyrazinones were converted into various [3,4-b] sulfolene pyridinones 19-21, serving as precursors for thermolytic conversion into the corresponding 5,6-dimethylene 2(1H)-pyridinone ortho-quinodimethanes. These were trapped in situ by reaction with various dienophiles. Tethering of precursor 19 with a dienophilic side chain attached to the 7-position of the [3,4-b] sulfolene pyridinone also enabled intramolecular cycloaddition when no rearrangement by 1,5-H-shift was viable.     

Synthesis of N-heterocyclic diols by diastereoselective pinacol coupling reactions

A series of 5-8 membered N-heterocyclic diols have been prepared from acyclic dicarbonyls via diastereoselective pinacol reactions whereby cis- or trans-diol stereoselectivity is controlled by the choice of low-valent metal reagent used.     

N-Arylation of 4-fluoro-5-trimethylsilyl-1H-pyrazole

The 1,3-dipolar cycloaddition reaction of fluoro(trimethylsilyl)acetylene prepared in situ with an excess of diazomethane smoothly proceeded to give the corresponding 4-fluoro-5-trimethylsilyl-1H-pyrazole in 84% yield. The copper iodide-catalyzed N-arylation of the fluorinated pyrazole with a variety of aryl iodides afforded N-aryl-4-fluoropyrazoles as desilylation products in good to excellent yields.     

Convenient synthesis of 5-methylene-4-substituted-2(5H)-furanones

A synthesis of novel 4-(substituted)benzyl-5-methylene-2(5H)-furanones involving Stobbe condensation of substituted aldehydes with ethyl levulinate followed by treatment with acetic anhydride in the presence of sodium acetate, has been developed.     

Efficient and rapid synthesis of 1-substituted-1H-1,2,3,4-tetrazoles in the acidic ionic liquid 1-n-butylimidazolium tetrafluoroborate

An efficient synthesis leading directly to 1-substituted-1H-1,2,3,4-tetrazoles from easily available amines and sodium azide in stoichiometric proportions using a room-temperature ionic liquid, namely, 1-n-butylimidazolium tetrafluoroborate in excellent yields is described. The inherent Brønsted acidity and high polarity of the IL results in a significant enhancement in the reaction rate.     

Isoquinolin-1(2H)-ones and 1,6-naphthyridin-5(6H)-ones by an N-acylation-SNAr sequence

A new synthesis of 2,3-dialkyl-4-carbomethoxyisoquinolin-1(2H)-ones and 6,7-dialkyl-8-carbomethoxy-1,6-naphthyridin-5(6H)-ones is reported. The process involves treatment of a β-enaminoester with 2-fluoro-5-nitrobenzoyl chloride, 2-fluorobenzoyl chloride or 2-chloronicotinoyl chloride followed by heating in the presence of base. The conversion, which proceeds by an N-acylation-S_NAr reaction sequence, affords 50–86% yields when R¹ is n-alkyl but ≤30% yields when R¹ is α-branched.     

Efficient synthesis of new 3-heteroaryl-1-functionalized 1H-indazoles

The efficient synthesis of novel 3-heteroaryl N-1-functionalized indazoles, via palladium cross-coupling reactions of ethyl (3-iodo-1H-indazol-1-yl)acetate with 2- and 3-pyrrolylboronic acids, 2-, 4- and 5-thiazolylstannanes, and other heteroarylmetallated derivatives are reported.     

Synthesis and reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole

The palladium-catalyzed cross-coupling reactions of 5-tributylstannyl-4-fluoro-1H-pyrazole with aryl iodides provided high yields of the corresponding 5-aryl-4-fluoro-1H-pyrazoles. Furthermore, these cross-coupling reactions proceeded smoothly under an atmosphere of carbon monoxide (CO) to afford the corresponding 5-acyl-4-fluoro-1H-pyrazoles as CO-insertion products.     

Novel synthesis of o-naphthothiophenequinone derivatives via regioselective Diels-Alder reaction

A novel procedure to construct o-naphthothiophenequinones has been achieved from readily available o-benzothiophenquinones and N-dienes via Diels-Alder reaction-aromatization sequence as key steps. The absolute regioselectivity was established via Diels-Alder reaction of o-benzothiophenquinones with rich electron N-dienes.     

5-Benzyl-1H-tetrazols from the reaction of 1-aryl-5-methyl-1H-tetrazoles with 1,2-dehydrobenzene

A series of 1-aryl-5-benzyl-1H-tetrazoles has been obtained during the reaction of 1-aryl-5-methyl-1H-tetrazoles with 1,2-dehydrobenzene. The mechanism of product formation was investigated.     

Transformation of methyl N-methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetates into 4-methylamino-5-nitrosopyrimidines and 9-methylpurin-8-ones

N-Methyl-N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetic acid methyl esters under the treatment of sodium alkoxides, depending on the nature of substituents in 6 position of the pyrimidine ring, undergo ring closure and rearrangement to give 6-substituted-4-methylamino-5-nitrosopyrimidines or 9-methylpurin-8-ones.