A practical improvement of crystallization-induced asymmetric transformation of allene-1,3-dicarboxylates

Enantiomerically pure allene-1,3-dicarboxylates were easily synthesized by using epimerization–crystallization of dissymmetric allene compounds, which were prepared from acetone-1,3-dicarboxylates and naturally abundant chiral alcohols, that is, (−)- and (+)-menthols, borneol, and isoborneol. After scrutinizing the crystallization of several allene-1,3-dicarboxylates in the presence of triethylamine, it was found that allene-1,3-dicarboxylate carrying bornyl groups was the most easily prepared as a single isomer because of it having suitable solubility to be crystallized in hexane at 0 °C to room temperature. Diels–Alder reaction of the enantiomerically pure allene-1,3-dicarboxylates and cyclic dienes, such as N-Boc-pyrrole and cyclopentadiene, afforded endo-adducts having the same configurations at two newly generated stereogenic centers.     

Biginelli-like reaction with dialkyl acetone-1,3-dicarboxylates: a remarkable case of steric control

A Biginelli-type condensation is described using dialkyl acetone-1,3-dicarboxylates as active methylene compounds for the preparation of monastrol analogues. Unexpectedly, the reaction with salicylaldehyde formed two different products depending on the ester alkyl group. This product dichotomy was found to be caused by the steric effects exerted by the alcohol terminus of the ester group in the active methylene component. Previous controversial results as to the structure of the Biginelli product 3 are also discussed.     

Construction of a pyrido[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine system on the basis of <Emphasis Type="Italic">N</Emphasis>-cyanobenzamidine and diethyl acetone-1,3-dicarboxylate

Nickel acetate promoted reaction of diethyl acetone-1,3-dicarboxylate with N-cyanobenzamidine led to ethyl 4-amino-6-ethoxycarbonylmethyl-2-phenylpyrimidine-5-carboxylate, upon treatment of which with RNH₂, the corresponding 6-(carbamoylmethyl)pyrimidines were obtained. Cyclization of the latter upon treatment with MeONa afforded 6-R-4-amino-7-hydroxy-2-phenylpyrido[4,3-d]pyrimidin-5(6H)-ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2212–2214, November, 2007.     

Reaction of N-Heterocycles with Acetylenedicarboxylates in the Presence of N-Alkylisatins or Ninhydrin. Efficient Synthesis of Spiro Compounds

Summary. The 1,3-dipolar intermediates generated by addition of isoquinoline, to dialkyl acetylenedicaboxylates are trapped by N-alkylisatins to produce dialkyl 1,2-dihydro-2-oxo-1-alkylspiro[3H-indol-3,2′-[2H,11bH][1,3]oxazino[2,3-a]isoquinoline]-3′,4′-dicarboxylates in excellent yields. The reaction of isoquinoline, quinoline, or pyridine with dimethyl acetylenedicarboxylate in the presence of ninhydrin led to dimethyl 1,2-dihydro-1,3-dioxospiro[3H-indene-3,2′-[2H,11bH][1,3]oxazino[2,3-a]isoquinoline]-3′,4′-dicarboxylate, dimethyl 1,2-dihydro-1,3-dioxospiro[3H-indene-3,3′[3H,4aH][1,3]oxazino[3,2-a]quinoline]-1,2-dicarboxylate, or dimethyl 1,2-dihydro-1,3-dioxospiro[3H-indene-3,2′-[2H,9aH]pyrido[2,1-b][1,3]oxazino]-3,4-dicarboxylate.     

Synthesis of oxoindolin-3-ylidene-1,3-dithioles

An efficient and one-pot synthesis of 2-(2-oxoindolin-3-ylidene)-1,3-dithiole-4,5-dicarboxylates by a three-component condensation reaction of isatins, carbon disulfide and dialkyl acetylendicarboxylates in the presence of Bu₃P is reported. Reaction of carbon disulfide and dialkyl acetylene dicarboxylates with acenaphthylene-1,2-dione, ninhydrine and pyrimidine-tetraone resulted in the formation of 2-(2-oxoacenaphthylen-1(2H)-ylidene)-1,3-dithiole-4,5-dicarboxylates, 2-(1,3-dioxo-1H-inden-2(3H)-ylidene)-1,3-dithiole-4,5-dicarboxylates and 2-(2,4,6-trioxotetrahydropyrimidin-5(6H)-ylidene)-1,3-dithiole-4,5-dicarboxylates, respectively, in the same conditions.     

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.     

Reactions of dimethyl and di-tert-butyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates with difunctional nucleophiles

The nature of the alkyl group in the ester moieties of dimethyl and di-tert-butyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates affects the direction of their reactions with difunctional nucleophiles. The dimethyl esters react with hydrazine hydrate to give the corresponding tetrahydroindazoles, while their tert-butyl analogs are converted under similar conditions into 6-hydrazones. Reactions of both dimethyl and di-tert-butyl 6-oxocyclohexane-1,3-dicarboxylates with hydroxylamine lead to formation of 6-hydroxyimino derivatives.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 10, 2004, pp. 1687–1691.Original Russian Text Copyright © 2004 by V. Gein, N. Gein, Potemkin, Krivenko.This revised version was published online in April 2005 with a corrected cover date.     

Reaction of dialkyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates with aliphatic amines

Benzylamine, phenethylamine, and homoveratrylamine reacted with dialkyl 2-aryl-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylates at the endocyclic carbonyl group with conservation of the enolic hydroxy group to give dialkyl 4-alkylamino-2-aryl-6-hydroxy-6-methylcyclohex-3-ene-1,3-dicarboxylates. The reaction of dimethyl 4-hydroxy-4-methyl-6-oxo-2-phenylcyclohexane-1,3-dicarboxylate with tryptamine was accompanied by dehydration with formation of dimethyl 4-[2-(1H-indol-3-yl)ethylamino]-6-methyl-2-phenylcyclohexa-3,5-diene-1,3-dicarboxylate, presumably due to basic properties of the indole nitrogen atom.     

Reaction of aromatic aldehydes with β-dicarbonyl compounds in a catalytic system: Piperidinium acetate-1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid

Condensation of aromatic (heteroaromatic) aldehydes with 1,3-dicarbonyl compounds under the 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF₄]) ionic liquid-piperidinium acetate catalytic system (0.2 equiv. of each component) in the absence of a solvent affords, depending on the structures of the reagents, 2-arylidene derivatives of methyl acetoacetate and acetylacetone, diethyl 2,4-bis(trifluoroacetyl)-3-phenylpentanedioate, or dimethyl 2-aryl-4-hydroxy-6-oxocyclohexane-1,3-dicarboxylates. The reactions of the resulting 2-arylidene derivatives with O-methylisourea in the [Bmim][BF₄] ionic liquid produced methyl 2-methoxy-4-methyl-6-aryldihydropyrimidine-5-carboxylates and 1-(2-methoxy-4-methyl-6-phenyldihydropyrimidin-5-yl)ethanone (mixtures of 3,6- and 1,6-dihydro isomers), which were transformed into the corresponding 3,4-dihydropyrimidin-2(1H)-one derivatives. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1199–1204, May, 2005.     

A novel attractive interaction in the Diels–Alder reaction of N-protected pyrroles with allene-1,3-dicarboxylates

The endo/exo selectivities of Diels–Alder reactions of N-protected pyrroles with allene-1,3-dicarboxylates were studied under Lewis acid assisted and thermal reaction conditions. A novel attractive effect between the N-protective carbonyl group of pyrrole and the ester group of allene-1,3-dicarboxylates operates to control the selectivity in the above Diels–Alder reaction. This new attractive effect to give the exo adduct is more effective than the Alder orbital effect.     

Catalytic hydrogenation of persubstituted <Emphasis Type="Italic">p</Emphasis>-nitrosophenols

Catalytic hydrogenation of dialkyl 2-hydroxy-4,6-dimethyl-5-nitrosobenzene-1,3-dicarboxylates over Pd/C gave the corresponding previously unknown dialkyl 5-amino-2-hydroxy-4,6-dimethylbenzene-1,3-dicarboxylates. The first-order rate constants for the hydrogenation process were found to be linearly related to steric constants of the alkyl groups.     

Synthesis and Structure of Diisopropyl 6-Hydroxy-6-methyl-4-oxocyclohexane-1,3-dicarboxylates and Their Reactions with Nucleophilic Reagents

Base-catalyzed reactions of isopropyl acetoacetate with aromatic and heterocyclic aldehydes afforded the corresponding diisopropyl 6-hydroxy-6-methyl-4-oxocyclohexane-1,3-dicarboxylates which were brought into reactions with mono- and difunctional nitrogen-containing nucleophiles. According to the X-ray diffraction data, diisopropyl 4-oxocyclohexane-1,3-dicarboxylates in crystal exist in the ketone form.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1039–1045.Original Russian Text Copyright © 2005 by Gein, Nosova, Potemkin, Aliev, Kriven’ko.     

σ-Skeletal-Rearrangement of Heptalenes: Thermal Transformation of Heptalene-1,2-dicarboxylates into Heptalene-1,3-dicarboxylates

It is shown that dimethyl heptalene-1,2-dicarboxylates undergo rearrangements at temperatures > 200° to yield the corresponding 1,3-dicarboxylates, which are isolated as the more stable 3,5-dicarboxylates. ²H- and ¹³C-labelling experiments with dimethyl 7-isopropyl-5,10-dimethylheptalene-1,2-dicarboxylate ( 1 ) which is rearranged into dimethyl 9-isopropyl-1,6-dimethylheptalene-3,5-dicarboxylates. ( 2 ) indicate that the reaction occurs by interchange of C(2) and C(3) in the heptalene skeleton of 1 . Thus, the transformation of 1 into 2 represents the first thermal σ-skeletal rearrangement of heptalenes. The structures of 1 and 2 are discussed in terms of an X-ray analysis and the spectral data.     

An Efficient One-pot Synthesis of 4H-Pyrrolo[3,2,1-ij]quinolines

Summary. Dialkyl 4H-pyrrolo[3,2,1-ij]quinoline-4,5-dicarboxylates are obtained in quantitative yields from the 1:1:1 addition reaction between triphenylphosphine, dialkyl acetylenedicarboxylates, and indole-7-carboxaldehyde.     

Ring-Opening 1,3-Aminochalcogenation of Donor–Acceptor Cyclopropanes: A Three-Component Approach

A 1,3-aminothiolation was realized by reacting 2-substituted cyclopropane 1,1-dicarboxylates with sulfonamides and N-(arylthio)succinimides. Under Sn(OTf)₂ catalysis the transformation proceeded smoothly to the corresponding ring-opened products bearing the sulfonamide in the 1-position next to the donor and the arylthio residue in the 3-position next to the acceptor. The procedure was extended to the corresponding selenium analogues by employing N-(phenylseleno)succinimides as an electrophilic selenium source.     

Investigation of reactions of the organozinc reagents prepared from zinc and dialkyl dibromomalonates with the derivatives of 2-arylmethyleneindan-1,3-dione and 5-arylmethylene-2,2-dimethyl-1,3-dioxane-4,6-dione

Organozinc compounds prepared from dialkyl dibromomalonates and zinc react with 2-arylmethyl-eneindan-4,6-diones, 5-arylmethylene-2,2-dimethyl-1,3-dioxane-4,6-diones, as well as with 2-[4-(1,3-dioxoindan-2-ylidenemethyl)phenyl]methyleneindan-1,3-dione and 5-[4-(2,2-dimethyl-4,6-dioxo-1,3-dioxane-2-ylidenemethyl)phenyl]methylene-2,2-dimethyl-1,3-dioxane-4,6-diones to form dialkyl 3-aryl-1′3′-dioxaspiro(cyclopropane-2,2′-indan)-1,1-dicarboxylates, dimethyl 3-aryl-6,6-dimethyl-5,7-dioxa-4,8-dioxaspiro[2,5]octan-2,2-dicarboxylates, dialkyl 2-{4-[3,3-bis (alkoxycarbonyl)-1′,3′-dioxaspiro(cyclopropane-2,2′-indan)-1-yl]phenyl}-1′,3′-dioxaspiro[cyclopropane-2,2′-indan]-1,1-dicarboxylates, and dialkyl 2-{4-[2,2-bis(alkoxycarbonyl)-6,6′-dimethyl-4,8-dioxo-5,7-dioxaspiro[2,5]oct-1-yl]phenyl}-6,6-dimethyl-4,8-dioxo-5,7-dioxaspiro[2,5]octan-1,1-dicarboxylate respectively.     

Synthesis of pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-7(8<Emphasis Type="Italic">H</Emphasis>)-one derivatives from 5-acetyl-4-aminopyrimidines and β-dicarbonyl compounds

Heating of 5-acetyl-4-aminopyrimidine derivatives with ethyl acetoacetate, ethyl benzoylacetate, and diethyl acetone-1, 3-dicarboxylate in the absence of a base gave the corresponding 6-acylpyrido[2, 3-d]pyrimidin-7(8H)-ones. Under analogous conditions, the reaction with ethyl malonate afforded ethyl 7-oxo-7, 8-dihydropyrido[2, 3-d]pyrimidine-6-carboxylates. The pyridone (rather than hydroxypyridine) structures of the pyridopyrimidines obtained were confirmed by IR spectroscopy.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 770–773, March, 2005.     

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.     

Cyanation of the Seven-Membered Ring of Diethyl Azulene-1,3-Dicarboxylate

Reaction of diethyl azulene-1,3-dicarboxylate with potassium cyanide in dimethoxyethane gave diethyl 4-cyano-, 6-cyano-, and 4,6-dicyanoazulene-1,3-dicarboxylates. This cyanation involved addition of acyanide ion to the seven-membered ring of azulene to form a cyclopentadienide ion, followed by oxidation.     

Synthesis and structure of (thio)semicarbazonocyclohexanedicarboxylates. Crystalline and molecular structure of diethyl 4-hydroxy-4-methyl-2-phenyl-6-thiosemicarbazonocyclohexane-1,3-dicarboxylate

Diethyl 2-aryl-4-hydroxy-4-methyl-6-(thio)semicarbazonocyclohexane-1,3-dicarboxylates were synthesized, and their structure was determined by ¹H and ¹³C NMR spectroscopy, including the HSQC technique. The molecular and crystalline structure of diethyl 4-hydroxy-4-methyl-6-thiosemicarbazono-2-phenylcyclohexane-1,3-dicarboxylate was determined by X-ray analysis.