Synthesis of 3-(quinolin-2-yl)indolizines through iodine-mediated sp3C–H functionalization of azaarenes

An efficient approach toward C–H bond activation using iodine-mediated sp³C–H bond functionalization for the synthesis of dialkyl 3-(quinolin-2-yl)indolizine-1,2-dicarboxylates and dialkyl 3-(quinolin-2-yl)pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylates through 1,3-dipolar cycloaddition reaction of nitrogen ylides with acetylenic esters is described.     

Regioselective Reaction of <Emphasis Type="Italic">N</Emphasis><Superscript>1</Superscript>-Benzyl-<Emphasis Type="Italic">N</Emphasis><Superscript>2</Superscript>-(4-nitrophenyl)ethanediamide and Acetylenic Esters

Summary. The regioselective reaction of N¹-benzyl-N²-(4-nitrophenyl)ethanediamide with dialkyl acetylenedicarboxylates or alkyl propiolates in the presence of triphenylphosphine leads to dialkyl 4-benzylamino-1-(4-nitrophenyl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylates or alkyl 4-benzylamino-1-(4-nitrophenyl)-2-oxo-5-pyrrolidinecarboxylates in good yields.     

Dipotassium Hydrogen Phosphate Powder Catalyzed Stereoselective O-Vinylation of 1-(2-Hydroxy-1-naphthyl)-1-ethanone

Protonation of the highly reactive 1:1 intermediates, produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates, by 1-(2-hydroxy-1-naphtyl)-1-ethanone leads to vinyltriphenylphosphonium salts, which undergo a Michael addition reaction with a conjugate base to produce corresponding stabilized phosphorus ylides. Dipotassium hydrogen phosphate powder was found to catalyze the conversion of stabilized phosphorus ylides to dialkyl (E, Z)-2-(1-acetyl-2-naphthyl)-2-butenedioates under thermal and microwave conditions in a solventless system.     

Dipotassium Hydrogen Phosphate Powder-Catalyzed Stereoselective Synthesis of N-Vinyl Pyrazoles in Solvent-Free Conditions

Protonation of the highly reactive 1:1 intermediates, which are produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates, by 3,5-dimethylpyrazol leads to vinyltriphenylphosphonium salts, which undergo a Michael addition reaction with a conjugate base to produce dialkyl 2-(3,5-dimethyl1H-pyrazol-1-yl)-3-(triphenylphosphoranylidene)butanedioates. Dipotassium hydrogen phosphate powder was found to catalyze the stereoselective conversion of dialkyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)-3-(triphenylphosphoranylidene) butanedioates to dialkyl 2-(3,5-dimethyl-1H-pyrazol-1-yl)-2-butenedioates in solvent-free conditions under microwave (0.6 KW, 3 min) and thermal (90°C, 60 min) conditions.     

HIGHLY STEREOSELECTIVE SYNTHESIS OF DIALKYL 2-ALKYLIDENE GLUTARATES

Nucleophelic substitution of dialkyl (E)-2-bromomethylene glutarates 2 by magnesium dialkyl cuprates generated in situ provided a regio and highly stereoselective methodology for the synthesis of dialkyl 2-alkylidene glutarates 3 in good yields.     

Regioselective Reaction of N1-Benzyl-N2-(4-nitrophenyl)ethanediamide and Acetylenic Esters

The regioselective reaction of N¹-benzyl-N²-(4-nitrophenyl)ethanediamide with dialkyl acetylenedicarboxylates or alkyl propiolates in the presence of triphenylphosphine leads to dialkyl 4-benzylamino-1-(4-nitrophenyl)-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylates or alkyl 4-benzylamino-1-(4-nitrophenyl)-2-oxo-5-pyrrolidinecarboxylates in good yields.     

One-pot, three-component reaction of isocyanides, dialkyl acetylenedicarboxylates, and non-cyclic anhydrides: synthesis of 2,5-diaminofuran derivatives and dialkyl (E)-2-[(N-acyl-N-alkylamino)carbonyl]-2-butenedioates

Abstract  

Isocyanides, dialkyl acetylenedicarboxylates, and non-cyclic anhydrides, for example acetic anhydride or benzoic anhydride, react in one-pot to afford 2,5-diaminofuran derivatives and dialkyl (E)-2-[(N-acyl-N-alkylamino)carbonyl]-2-butenedioates in fairly good yields at room temperature.     

Reactions of N,N-(dialkyl)arylthioacetamides with dialkyl acetylenedicarboxylates

2-(Alkoxycarbonylmethylidene)-4-aryl-5-(dialkylamino)thiophen-3(2H)-ones were synthesized by condensation of N,N-(dialkyl)arylthioacetamides with dialkyl acetylenedicarboxylates. Intermediate substituted vinylic sulfides were isolated. When heated or in the presence of an acid or a base, they undergo cyclization into thiophenes.     

Solvent-Free Synthesis of Novel Highly Functionalized Dihydroanthra[1,2-b]furan-6,11-dione Derivatives

A convenient and environmentally friendly solvent-free procedure has been developed to react 1,5-dihydroxyanthraquinone with dialkyl acetylenedicarboxylates in the presence of triphenylphosphine in one pot to afford novel dialkyl (E)-2-{1,5-dihydroxy-6-[3-methoxy-1-(methoxycarbonyl)-3-oxo-2-(triphenyl-λ ⁵-phosphanylidene)propyl]-9,10-dioxo-9,10-dihydro-2-anthracenyl}-2-butanedioate 3a–c. As a result of intramolecular nucleophilic attack at 90 °C, novel dialkyl (E)-2–{2,7-dihydroxy-3-[2-methoxy-2-oxo-1-(triphenyl-λ ⁵ phosphanylidene)ethyl]-6,11-dioxo-6,11-dihydroanthra[1,2-b]furan-8-yl}-2-butanedioates 4a–c were produced in good yield.     

Triphenylphosphine Mediated Efficient Synthesis of 4-Substituted-1-methyl-2,5-dioxo-3-imidazolines

Summary.  Stable crystalline phosphorus ylides are obtained in excellent yields from the 1:1:1 addition reaction between 1-methylparabanic acid (1-methylimidazoline-2,4,5-trione) and dialkyl acetylenedicarboxylates in the presence of triphenylphosphine. These ylides exist in solution as a mixture of two geometric isomers. This is due to the restricted rotation around the carbon–carbon partial double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group. These ylides undergo smooth intramolecular Wittig reaction followed by an electrocyclic ring opening to produce dialkyl (E)-2-(1-methyl-2,5-dioxo-3-imidazolin-4-yl)-but-2-enedioates in good yields. Corresponding author. E-mail: isayavar@yahoo.com Received March 26, 2002; accepted (revised) April 24, 2002     

A Facile One‐Pot Synthesis of Functionalized 1,5‐Dihydro‐2H‐[1]benzopyrano[2,3‐b]pyridin‐5‐ones

The highly reactive 1 : 1 intermediate generated in the reaction between dialkyl acetylenedicarboxylate (=but‐2‐ynedioic acid dialkyl ester) 4 and triphenylphosphine was trapped by 2‐amino‐4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehydes 5 to yield highly functionalized dialkyl‐1,5‐dihydro‐5‐oxo‐1‐phenyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,3‐dicarboxylates in high yield.     

Efficient Synthesis of Dialkyl (2Z)‐2‐[(E)‐1‐Aryl‐2‐(3‐arylquinoxalin‐2‐yl)ethenyl]but‐2‐enedioates

The reaction of dialkyl acetylenedicarboxylates 4 with 1‐aryl‐2‐[(3‐arylquinoxalin‐2(1H)‐ylidene)ethanones 3 in the presence of Ph₃P leads to dialkyl (2Z)‐2‐[(E)‐1‐aryl‐2‐(3‐arylquinoxalin‐2‐yl)ethenyl]but‐2‐enedioates 1 in good yields.     

One-pot synthesis of phosphorylsuccinates and triphenylphosphanylidenesuccinates containing a thioamido group

Abstract

Stable substituted dialkyl phosphorylsuccinates were synthesized, as a mixture of two diastereoisomers, in high yields using one-pot reaction of dialkyl acetylenedicarboxylates, trialkyl phosphites, and thioamides in CH₂Cl₂ at room temperature. Using triphenylphosphine instead of phosphites, afforded stabilized triphenylphosphanylidenesuccinates. DFT calculations at B3LYP/6-31?+?G(d) level indicated that among four possible conformational diastereoisomers of dimethyl 2-(dimethoxyphosphoryl)-3-ethanethioamidosuccinate, the (2R,3S) and (2S,3S) diastereomers are the most stable forms.     

Reaction of γ-benzylideneaminopropanol with dialkyl phosphorochloridites

Reactions of dialkyl phosphorochloridites with 3-(N-benzylideneamino)propan-1-ol follow two pathways giving rise to linear dialkyl 1-(3-chloropropylamino)benzylphosphonates and diastereomeric cyclic 2-alkoxy-2-oxo-3-phenyl-1,4,2-oxazaphosphepanes. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1453–1455, June, 2005.     

Synthesis of 4,4‐Disubstituted‐4H‐benzo[d][1,3]oxathiin‐2‐ones,a New Class of Compounds

4,4‐Dialkyl and 4,4‐diaryl‐4H‐benzo[d][1,3]oxathiin‐2‐ones were synthesized by the reaction of 2‐(mercapto‐phenyl)‐dialkyl‐ (or diaryl)‐methanol with CDI in excellent yield. The 2‐(mercaptophenyl)‐dialkyl‐ (or diaryl)‐methanols were prepared by the reaction of commercially available methylthiosalicylate with an appropriate alkyl or aryl Grignard reagent.     

One‐Pot Synthesis of Functionalized 2H‐Chromene (=2H‐1‐Benzopyran) Derivatives via a Three‐Component Reaction between a CH‐Acid,a Dialkyl Acetylenedicarboxylate,and Methyl Chloroglyoxylate or Benzyl Carbonochloridate Mediated by Triphenylphosphine

An effective route to functionalized 2H‐chromene (=2H‐1‐benzopyran) derivatives 4 is described (Scheme 1). This involves the reaction of a 1,1‐diactivated alkene, resulting from the reaction of dimedone (=5,5‐dimethylcyclohexane‐1,3‐dione; 1a ) with methyl chloroglyoxylate (ClC(O)COOMe), benzyl carbonochloridate (ClC(O)OCH₂Ph) or 3,5‐dinitrobenzoyl chloride (3,5‐(NO₂)₂C₆H₃C(O)Cl), and a dialkyl acetylenedicarboxylate (=dialkyl but‐2‐ynedioate) in the presence of Ph₃P which undergo intramolecular Wittig reaction to produce 2H‐chromene derivatives (Scheme 1).     

A convenient synthesis of functionalized pyrazolones bearing a highly twisted 1,3-butadiene moiety with skew geometry

Abstract

The four-component reaction among arylhydrazine, alkyl acetoacetate derivatives, alkyl isocyanides, and dialkyl acetylenedicarboxylates, leading to the formation of dialkyl 2-[(Z)-(alkylamino)(3-alkyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)methyl] fumarates is described. The structure of target compounds was confirmed using X-ray diffraction study. These pyrazolone derivatives contain a highly twisted exocyclic 1,3-butadiene moiety with skew (??=?87°) geometry.     

Dipotassium-Hydrogen-Phosphate-Powder-Catalyzed Stereoselective C-Vinylation of Diphenylacetonitril

Protonation of the highly reactive 1:1 intermediates, produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates by diphenylacetonitril, leads to the vinyltriphenylphosphonium salts, which undergo a Michael addition reaction with a conjugate base to produce the corresponding stabilized phosphorus ylides. Dipotassium hydrogen phosphate powder was found to catalyze the conversion of the stabilized phosphorus ylides to dialkyl(Z)-2-[cyano (diphenyl)methyl]-2-butenedioates under thermal and microwave conditions in a solventless system.     

Synthesis of 3-Substituted Dialkyl 2-Aroyl-2-ethylcyclopropane-1,1-dicarboxylates by the Reformatsky Reaction

1-Aryl-2,2-dibromobutan-1-ones react with zinc and dialkyl arylmethylene- or isobutylidenemalonates to give dialkyl 2-aroyl-3-phenyl(isopropyl)-2-ethylcyclopropane-1,1-dicarboxylates which are formed mainly as Z isomers.     

Regioselective hydrolysis of ketenimines derived from NH-acids and acetylenic esters in the presence of tert -butyl isocyanide under neutral conditions

The regioselective hydrolysis of ketenimines derived from NH-acids, such as 2,2,2-trichloro-N-phenylacetamide or ethyl-2-anilino-2-oxoacetates and acetylenic esters in the presence of tert-butyl isocyanide in a THF/H₂O system (1/1) without any catalysis leads to a diastereomeric mixture of dialkyl 2-[(tert-butylamino)carbonyl]-3-[(2,2,2-trichloroacetyl)anilino]succinates and dialkyl 2-[(tert-butylamino)carbonyl]-3-[2-ethoxy-2-oxoacetyl)anilino]-succinates in good yields. Dynamic NMR effects were observed in the ¹³C NMR spectra of diethyl 2-[(tert-butylamino)carbonyl]-3-[(2,2,2-trichloroacetyl)anilino]succinate as a result of restricted rotation around the N-aryl single bond. The free energy of activation (ΔG ^#) for this process is 37.9 kJ mol⁻¹ which leads to an observable atropisomerism.