Facile microwave-mediated transformations of 2-butene-1,4-diones and 2-butyne-1,4-diones to furan derivatives

Several di- and triarylfuran derivatives were prepared in high yields from but-2-ene-1,4-diones/but-2-yne-1,4-diones using formic acid in the presence of a catalytic amount of palladium on carbon and in poly(ethylene glycol)-200 medium in a one-pot operation under microwave irradiation (1-5 min).     

Silver triflate catalyzed tandem heterocyclization/alkynylation of 1-((2-tosylamino)aryl)but-2-yne-1,4-diols to 2-alkynyl indoles

Don't cross me! 2-Alkynyl indoles were prepared efficiently by the AgOTf-catalyzed tandem heterocyclization/alkynylation of 1-(2-tosylamino)aryl)but-2-yne-1,4-diols under mild conditions (see scheme). The attractiveness of this approach lies in the fact that both the indole ring and alkyne side chain of the N-heterocycle are sequentially formed from low cost, readily available, and ecologically benign starting materials. It also provides the first route to this synthetically valuable class of compounds that is not based on a cross-coupling strategy.     

Use of [hydroxy(tosyloxy)iodo]benzene in a novel and facile synthesis of 1,4-diaryl-2-(arylamino)but-2-ene-1,4-diones

The reaction of acetophenones 1 with [hydroxy(tosyloxy)iodo]benzene followed by treatment of the resulting α-tosyloxyacetophenones 2 thus formed with anilines 3 in the presence of sodium carbonate in ethanol provides a novel one-pot synthesis of 1,4-diaryl-2-(arylamino)but-2-ene-1,4-diones 4.     

Indium trichloride catalyzed sp C–H bond functionalization of 2-alkyl azaarenes under microwave irradiation

Microwave promoted indium trichloride (10 mol %) catalyzed sp³ C–H bond functionalization of 2-alkyl azaarenes 1 or 4 has been observed to construct C–C bond either with but-2-ene-1,4-diones 2 or (E)-3-(2-oxo-2-phenylethylidene)indolin-2-one (6) giving access to 2-((quinolin-2-yl)methyl)butane-1,4-diones 3, 2-((pyridin-2-yl)methyl)butane-1,4-diones 5, or 3-(quinolin-2-yl)propan-2-yl)indolin-2-ones 7 in good yields using 1,4-dioxane as solvent.     

2,3-二氢-1,4-酞嗪二酮的微波合成

以邻苯二甲酸酐和肼类化合物为原料,用微波辐射合成了6种2,3-二氢-1,4-酞嗪二酮类化合物,其结构经^1H NMR和^13C NMR表征。     

Synthesis of 5-(phenylsulfanyl)-1,4-dihydropyrazine-2,3-diones via an unexpected microwave-assisted cascade reaction

An unprecedented route for the synthesis of N-1 substituted 5-(phenylsulfanyl)-1,4-dihydropyrazine-2,3-diones is disclosed starting from 5-chloro-3-(phenylsulfanyl)pyrazin-2(1H)-ones. The method comprises treatment of various 5-chloro-3-(phenylsulfanyl)pyrazin-2(1H)-ones with Na₂CO₃ in water under microwave irradiation providing the respective 5-(phenylsulfanyl)-1,4-dihydropyrazine-2,3-diones in good yields, via hydrolysis of the thioether bond and subsequent nucleophilic displacement of the chlorine by the in situ generated thiophenol. The obtained compounds are excellent precursors for the diversity oriented synthesis of pharmacologically active α,β-dicarbonyl compounds.     

An efficient microwave accelerated three component reaction of phenacyl azides and pyridinium phenacyl salts: A facile greener approach to 2-amino-2-ene-1,4-diones/pyrrolidin-2-ones

Abstract

A mild and efficient base promoted, microwave assisted, green synthesis of 2-amino-2-ene-1,4-diones has been described by the decomposition of phenacyl azides followed by treatment with pyridinium salts of phenacyl bromides in aqueous media. A diverse range of substrates bearing electron-releasing and electron-withdrawing substituents were well tolerated and delivered corresponding 2-amino-2-ene-1,4-diones in good yields. Synthesized 2-amino-2-ene-1,4-diones have been further explored in the synthesis of various substituted 4-hydroxypyrrolidin-2-ones.     

Reactions of but-2-yne-1,4-diylbis(triphenylphosphonium) dihalides with SH- and NH-nucleophiles

But-2-yne-1,4-diylbis(triphenylphosphonium) diiodide reacts with 2-sulfanylethan-1-ol in the presence of triethylamine to form a 1 : 1 adduct. Under similar conditions, ethane-, butane- and 2-methylbutane- 1-thiols form [4-(alkylsulfanyl)buta-1,3-dien-1-yl]triphenylphosphonium iodides, probably via β-cleavage of the original salt involving vinylethynyl intermediate. Features of the reaction of but-2-ynebisphosphonium salt with 3,5-dimethylpyrazole, hydrazine and its derivatives have been studied.     

A mild conversion of phenylpropropnoid into rare phenylbutanoids: (E)-4-(2,4,5-trimethoxyphenyl)but-1,3-diene and (E)-4-(2,4,5-trimethozypheny)but-1-ene occuring in Zingiber cassumunar

(E)-4-(2',4',5'-trimethoxyphenyl)but-1,3-diene (4) and (E)-4-(2',4',5'-trimethoxyphenyl)but-1-ene (6), bioactive phenylbutanoids of Zingiber cassumunar, were synthesized exclusively with trans geometry. Treatment of methylmagnesium iodide with (E)-2',4',5'-trimethoxycinnamaldehyde (2), an oxidized product of abundantly available toxic (Z)-phenylpropanoid (1) of Acorus calamus, gave (E)-4-(2',4',5'-trimethoxyphenyl)but-3-en-2-ol (3) which upon dehydration with copper sulphate/silica gel under microwave irradiation for 3 min afforded 4 in 58% yield. Further, catalytic hydrogenation of 4 with 10% Pd/C afforded 4-(2',4',5'-trimethoxyphenyl)butane (5) which upon dehydrogenation with DDQ/SiO2 afforded hypolipidemic 6 in 54% yield.     

Enantiodifferentiating tetrahydrofuranylation of but-3-enyl carboxylates using optically active hypervalent iodine(III) reagents via a 1,3-dioxan-2-yl cation intermediate

Optically active methyl 2-[2-(diacetoxyiodo)phenoxy]propanoate and its derivative were prepared and used for oxygenation of but-3-enyl carboxylates leading to tetrahydrofuran-3-yl carboxylates as an enantiomerically enriched form.     

Domino Michael-Aldol reactions on 1,4-diarylbut-2-ene-1,4-diones with methyl acetoacetate furnish methyl 2-aroyl-4- hydroxy-6-oxo-4-arylcyclohexane-1-carboxylate derivatives

Domino Michael-Aldol reactions on 1,4-diaryl-2-butene-1,4-diones with methyl acetoacetate in the presence of activated Ba(OH)(2) furnished methyl (1R*,2S*,4S*)-2-aroyl-4-hydroxy-6-oxo-4-arylcyclohexane-1-carboxylate derivatives in a stereo- and regiospecific manner. While treatment of these cyclohexanecarboxylate products with TsOH resulted in the dehydrated and decarbomethoxylated cyclohexenone derivatives, the reaction with NaOMe furnished 3,5-disubstituted phenols via dehydration, decarbomethoxylation, and dehydrogenation. NaCl/DMSO under microwave irradiation transformed the cyclohexanecarboxylate products to the 7-hydroxyisobenzofuranone derivatives.     

Formic acid oxidatively cleaves 1,2,3,4-tetraaryl-2-butene-1,4-diones to 1,2-diaryl-1,2-ethanediones under microwave irradiation

Formic acid oxidatively cleaves 1,2,3,4-tetraaryl-2-butene-1,4-diones (1,2-aroylstilbenes) to 1,2-diaryl-1,2-ethanediones (benzils) under microwave irradiation. Mechanistic probing revealed that formic acid incorporates one of its oxygen atoms into benzil.     

Synthesis and search for compounds with hemostatic activity in the series of 4-(het)aryl-4-oxobut-2-enoic acid derivatives

New 4-aryl-2-(4-arylamino)-1-(piperazin-1-yl)but-2-ene-1,4-diones and 2-{[2-(3-R-adamantan-1-yl)-2-oxoethylidene]hydrazinyl}-4-(het)aryl-4-oxobut-2-enoic acids were synthesized and used to obtain water-soluble compounds. Their influence on the blood coagulation system was studied, which revealed compounds with a high hemostatic activity and a low acute toxicity. A relationship between structure and pharmacological effect of the synthesized compounds was established.     

Peculiarities of the behavior of succinyl dichloride in Friedel-Crafts reaction with thiophenes*

The reactions of thiophene, 2-methyl-, and 2-bromothiophene with succinyl dichloride in the presence of AlCl₃, TiCl₄, and SnCl₄ have been studied. The effect of the acylation conditions, the relative amounts and nature of the Lewis acid on the ratio and yields of the 1,4-di(2-thienyl)-1,4-diones and 4-oxo-4-(2-thienyl)butyric acids formed have been demonstrated. Under the reaction conditions, the formation of 4,4-di(2-thienyl)but-3-enoic acids (the main products in many cases) and also 4,4-di(2-thienyl)-butyrolactones was demonstrated.     

Preparation of Isoquinolin-(2(1H)-yl)but-2-enedioate Derivatives

One-pot, three-component reactions of isoquinoline, dimethyl/diethyl acetylenedicarboxylate, and indole, carbazole, pyrazole, or imidazole gave dimethyl/diethyl 2-(1-(1H-indol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate, dimethyl/diethyl 2-(1-(9H-carbazol-9-yl)isoquinolin-2(1H)-yl)but-2-enedioate, dimethyl 2-(1-(1H-pyrazol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate, or dimethyl 2-(1-(1H-imidazol-1-yl)isoquinolin-2(1H)-yl)but-2-enedioate respectively in good to excellent yields.     

Construction of Polyheterocyclic Compounds by Lewis Acid Mediated Intramolecular [3+2] Cycloaddition Reaction

An efficient domino approach has been developed for the synthesis of polyheterocyclic derivatives constituting pyrrole moiety. Lewis acid catalyzed reaction of 2-substituted-2-hydroxy-indane-1,3-diones and 1,4-benzoxazinone derivatives resulted in the formation of polyheterocyclic compounds under metal-free and mild conditions in good to excellent yield. The reaction is highly regioselective for C−C and C−N bond construction proceeded via intramolecular [3+2] cycloaddition reaction. The protocol is highly efficient, obviates column chromatography and the products are obtained by simple filtration followed by washing with solvent.     

Unsubstituted bicyclo[1.1.0]but-2-ylcarbinyl cations

A synthesis for the unsubstituted bicyclo[1.1.0]but-2-ylmethanols (endo- and exo-9) from 1,3-butadiene has been developed. Solvolyses of their sulfonates 10 and 11 took entirely different courses, as the endo compound 10 gave rise exclusively to rearranged products such as cyclopent-3-en-1-ol (14), while the exo compound 11 underwent only the substitution of the tosylate group with complete retention of the exo-bicyclo[1.1.0]but-2-ylmethyl skeleton. Under solvolytic conditions, 10 reacted at very similar rates to the corresponding monocyclic substrate, that is, cyclopropylcarbinyl mesylate (19); in contrast, 11 reacted only three times as fast as n-butyl tosylate and about 1000-fold slower than 10. The nature of the bicyclo[1.1.0]but-2-ylcarbinyl cations has been probed by quantum chemical calculations. Whereas, the exo isomer (exo-18) corresponds to a local energy minimum, the endo isomer is only a transition state [endo-18(TS)] for an automerization of the nonclassical cyclopent-3-en-1-yl cation (13) and converts into 13 by a Wagner-Meerwein rearrangement. The most favorable isomerization of exo-18 also leads to 13 but via a transition state resembling the 2-vinylcycloprop-1-yl cation [25(TS)]. On the introduction of methyl groups at positions 1 and 3 of exo-18, the cation is no longer an energy minimum and it becomes a transition state [27(TS)] for an automerization of the nonclassical 1,3-dimethylcyclopent-3-en-1-yl cation (28). The large effect of the methyl substitution rationalizes the puzzling results of the previous product and rate studies, which utilized various substituted derivatives of bicyclo[1.1.0]but-2-ylcarbinyl sulfonates as substrates.     

5-Endo-dig electrophilic cyclization of 1,4-disubstituted but-3-yn-1-ones: regiocontrolled synthesis of 2,5-disubstituted 3-bromo- and 3-iodofurans

[reaction: see text] 5-Endo-dig electrophilic cyclization of 1,4-diaryl but-3-yn-1-ones with N-bromosuccinimide or N-iodosuccinimide/acetone and iodine monochloride/CH(2)Cl(2), at room temperature, in the absence of base, provides 3-halo-2,5-diarylfurans with excellent regiocontrol and high yields (81-94%).     

新型(Z)-2-[(苯氧基)(芳基)]次甲基-2-丁烯酸酯类化合物的合成

以三苯基膦为催化剂,氮气保护下在苯中实现了取代苯酚与α-取代-2,3-丁二烯酸酯的β'-极化加成反应,合成了16个新型(Z)-2-[(苯氧基)(芳基)]次甲基-2-丁烯酸酯类化合物,其结构经1H NMR,13C NMR和MS(ESI)表征。     

Easy access to N,N-bis(but-3-enyl)-, N-allyl-N-(but-3-enyl)-, and N-(but-3-ynyl)-N-(but-3-enyl)-amines

N,N-Bis(but-3-enyl)amines 5a-i were prepared in overall 74% yield from 1-(triphenylphosphoroylideneaminoalkyl)benzotriazole using an aza-Wittig reaction with aldehydes followed by a double Grignard reaction with allylmagnesium bromide. Use of vinyl or 1-propynylmagnesium bromide and allylmagnesium bromide in a sequential fashion also formed the expected doubly unsaturated amines 9a,b and 12, respectively.