Synthesis of optically active dihydropyrans from asymmetric [4 + 2] cycloaddition of β,γ-unsaturated α-ketoesters with allenic esters

β-Isocupreidine (β-ICD) catalyzed asymmetric [4 + 2] cycloaddition of β,γ-unsaturated α-ketoesters with allenic esters afforded ester-substituted functionalized dihydropyran derivatives in high yields along with high enantioselectivities under mild conditions.     

DABCO-catalyzed regioselective cyclization reactions of β,γ-unsaturated α-ketophosphonates or β,γ-unsaturated α-ketoesters with allenic esters

Highly efficient DABCO-catalyzed [4 + 2] cycloaddition of β,γ-unsaturated α-ketophosphonates or β,γ-unsaturated α-ketoesters with allenic esters gives the corresponding highly functionalized tetrahydropyran and dihydropyran derivatives in good to excellent yields and moderate to good regioselectivities under mild conditions.     

Arbeiten über Phosphorsäure- und Thiophosphorsäureester mit einem heterocyclischen Substituenten. 7. Mitteilung. Thio- und Dithiophosphorsäureester von der Art des GS 13005 mit einem analogen oder homologen heterocyclischen Ring

To complete results presented in this and in previous papers of this series as well as published in patents of other authors a review is given on known and new variations of the heterocyclic moiety in GS 13005 type thio- and dithiophosphoric acid esters ( 1, 2 ) by modification of the 1,3,4-thiadiazol-2(3H)-one ring 5 and by its replacement by analogue five- and homologue six-membered rings. Among new esters of this type some containing the pyrazolinone ring 3 or a 2-alkoxy-4H, 6H-1,3,4-thiadiazin-5-one ring 10 (homologue of the original 5-methoxy-1,3,4-thiadiazol-2(3H)-one ring in GS 13005) show no remarkable pesticidal activity, some others containing a pyrazolering 7 or a 3(2H)-pyridazinonc ring 8 are moderately to highly active but toxic to inauinials in the same proportion. Attempts to prepare seven-membered 2-alkoxy- and 2-alkylthio-6,7-dihydro-l, 3,4-thiadiazepin-S(4H)-ones 11 , Z-rnethoxy-l,3,4-thiadiazepin-S(4H)-one 12 (ring vinylogue of the original 5-methoxy-l,3,4-thiadIazol-2(3H)-one ring in GS 13005) and its 7-methyl-derivative have been unsuccessful due to unexpected side reactions, such as: five-ring closure of 3-(3-chloropropionyl)-thio- and -dithiocarbazic acid esters 22 to pyrazolidinone derivatives 23 , pyrazolinone ring closure of a 3-(acetoacety1)-thiocarbazic acid O-methyl ester derivative 26 , bromine attack on sulfur in 3-(2-alkenoyl)-thiocarbazic O-methyl esters 29 instead of bromine addition at the double bond, and halogen splitting off without ring closure in 3-(2,3-dihalogeno-alkanoyl) -thiocarbazic O-methyl esters 30 prepared by acylation of thiocarbazic acid O-methyl ester with dihalogeno-alkanoyl-chlorides.     

Facile Synthesis of Nicotinic Acid Derivatives with Unsymmetrical Substitution Patterns

Abstract

Two novel methods for synthesis of nicotinic acid derivatives with unsymmetrical substitution patterns were presented via ketene dithioacetals. The ketene N,S-acetals 2 reacted with β-ketoesters or β-cyanoesters to give 4-amino-5-cyano-2-alkyl-6-methylthio-nicotinic acid derivatives 3 or 2,4-diamino-5-cyano-6-methylthio-nicotinic acid ethyl ester 4. However, 6-amino-5-cyano-2-alkyl-4-methylthio-nicotinic acid esters 6 were obtained by the reaction of the ketene dithioacetals 1 and β-amino-crotonates.     

Rhodium-Katalysierte Isomerisierungen von 2-Methylidenglutarsäureestern zu Methylglutaconsäureestern

The Rhodium(III)-catalyzed thermal isomerization of 2-methylidenglutaric acid esters affords predominantly mixtures of cis/trans-2-methylglutaconic acid esters ( 2, 3 ) which upon slow distillation isomerize completely into the cis-esters ( 2 ). Saponification of 2 yields trans-2-methylglutaconic acid ( 5 ). Attempts to prepare the acid chloride of 5 produces 6-chloro-5-methylpyrone-2 ( 9 ) or 6-chloro-3-methylpyrone-2 ( 10 ) which react with anilines to N-substituted derivatives of trans-4-methylglutaconic acid amides ( 11 ). The thermal isomerizations of the respective esters are discussed in terms of 1,5-hydrogen shifts in their ester enol structures.     

New tetracyclic compounds containing the β-carboline moiety

Oxidation of 1-methyl-3-methoxycarbonyl-β-carboline with selenium dioxide gave 1-formyl-3-methoxycarbonyl-β-carboline II . Compound II reacted with acetic or propionic anhydride to give easily the 2-methoxycarbonyl-6H-indolo[3,2,1-d,e][1,5]naphthyridin-6-ones III ; reaction of II with some primary amines led to the formation of the Schiff bases IV , which were reduced to the 1-aminomethyl-3-methoxycarbonyl-β-carbolines V with sodium borohydride. Cyclization of V with aqueous formaldehyde led to the pyrimido[3,4,5-lm]pyrido[3,4-b]indoles VI . Analogously, cyclization with formaldehyde, acetone or 1,1′-carbonyldiimidazole of the 3-aminomethyl- 1,2,3,4-tetrahydro-β-carbolines VIII , obtained by reaction of 3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline VII with amines followed by lithium aluminium hydride reduction of the resulting amides, gave the imidazo[1′,5′-1,6]pyrido[3,4-b]indoles IX and X . Dieckmann cyclization of 3-methoxycarbonyl-2-[(3-ethoxycarbonyl)-1-propyl]-1,2,3,4-tetrahydro-β-carboline XI led to a 1:1 mixture of the β-ketoesters XII and XIII , which underwent deethoxycarbonylation to 5,6,8,9,10,11,11a,12-octahydroindolo[3,2-b]quinolizin-11-one XIV . Finally, the polyphosphoric acid (or esters) catalyzed cyclization of the N-acyl derivatives XVI of 3-hydrazinocarbonyl-β-carboline XV led smoothly to the 3-(1,3,4-oxadiazol-2-yl)-β-carbolines XVII .     

Réactions de cyclisation de pentynyl-2 pyrimidones-4

Acetylenic amindines HC≈?C·(CH₂)_n·C(?NH)NH₂ give, by condensation with β-ketoesters, pyrimidones substituted on carbon 2 by an acetylenic chain. Two types of evolution are observed when compounds are heated without any catalyst. The minor route is a cyclization by attack on a triple bond by the amidic nitrogen atom. The main reaction is a cycloaddition involving the non activated triple bond and an azadienic system, leading to non isolated tricyclic intermediates which retrocyclize to stable bicyclic compounds.     

Synthèse de nouvelles amidines bicycliques . Dérivés de la pyrimidine,de la quinazoline et de la diazépine-1,3

The synthesis of pyrrolo[1,2-α] pyrimidines is described. Several homologous compounds contain pyridine or azepine instead of pyrrole ring. They are obtained by cyclization of iminolactams with β-ketoesters, αβ-unsaturated esters, aldehydes or ketones, or diketene. The possibility of obtaining isomers is discussed.     

Chemistry of bicyclic 5-6 systems: Synthesis of oxazolo[3,2-a]pyridines and their salts with a ring-junction nitrogen atom

The present review highlights the synthetic procedures reported for the preparation of oxazolo[3,2-a]pyridines as a class of 5-6 bicyclic heterocycles with a nitrogen atom at the ring junction. The different sections included the synthesis of the investigated analogs through the reactions of (1) β-ketoesters with α,β-unsaturated ketones (2) δ-oxoacids or esters or unsaturated carboxylic acids with glycinol derivatives (3) unsaturated ketoesters with enamines (4) ethoxymethylenes with amidoglycinol derivatives (5) pyridinium salts with phenylglycinol (6) Multicomponent reactions, and (7) Synthesis of tetracyclic systems. The aim of the present study is to demonstrate a synopsis of the synthesis of compounds containing oxazolo[3,2-a]pyridine skeleton with high yields using readily and accessible starting materials, and efficient synthetic routes until now. The stereochemistry of the obtained enantiopure heterocycles, the isolation of the isomers and the reaction mechanisms of the unexpected products are discussed.     

Synthesis of ethyl 4,5-disubstituted 2-azido-3-thiophenecarboxylates and use in the synthesis of thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4H)-ones

New heterocyclic azides, ethyl 2-azido-4-R¹-5-R²-3-thiophenecarboxylates, were synthesized by diazotization of 2-aminothiophenes and subsequent treatment with sodium azide. The reactions of these heterocyclic azides with β-ketoesters and activated acetonitriles were studied. The derivatives of thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidine, a new ring system, were prepared in high yields via an anionic hetero-domino reaction.     

Ru(II)-catalyzed α-sulfonamidation of cyclic β-ketoesters with sulfonyl azides

α-Sulfonamidation of β-ketoesters with sulfonyl azide has been developed for the first time using a catalytic amount of Ru(II) complex to produce the 1-oxo-2-(sulfonamido)-2,3-dihydro-1H-indene-2-carboxylate and 1-oxo-2-(sulfonamido)-1,2,3,4-tetrahydronaphthalene-2-carboxylate derivatives in good yields. This method also works well with α-iodotetralones to afford the N-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)sulphonamide derivatives under similar conditions.     

One-pot,three-component synthesis of highly functionalized pyrimidone derivatives and access to indole fused pyrimidones via palladium-catalyzed intramolecular Heck reaction

A simple and facile approach to highly functionalized pyrimidone derivatives and indole fused pyrimidones has been developed. The synthesis of substituted pyrimidone derivatives in moderate to good yields involves [4+2] cycloaddition of 1,4-dipoles generated from α,β-unsarurated imines and dimethyl acetylenedicarboxylate (DMAD) with isocyanates as dipolarophiles. Furthermore, the pyrimidones resulted from 2-bromophenyl isocyanate could be transformed into various indole fused pyrimidones via intramolecular palladium-catalyzed Heck reaction under different conditions.     

Thermische Umlagerungen von halogensubstituierten Aryl-propargyläthern

7-Chloro-2-chloromethyl-benzofuran (13) and 3, 8-dichloro-2 H-1-benzopyran (12) are the main products from the thermal rearrangement (230–260°) of 2, 6-dichlorophenyl propargyl ether (7) . Compounds 17 , 18 and 19 are also formed, but in much smaller amounts (scheme 2 and table 1). However, in the case of the bromo-compounds 8 and 9 the rearrangement products are the benzofuran derivatives 21 and 22 , containing one bromine atom less per molecule (scheme 4). The corresponding naphthyl propargyl ethers 10 and 11 can be rearranged much more easily (180°) to the halogeno-naphthofurans 24 and 26 respectively. In the case of the bromo-ether 11 , 2-methyl-naphtho[2, 1-b]furan (25) is also formed (scheme 5). If the propargylic hydrogen atoms in 7 and 11 are replaced by deuterium atoms, then after rearrangement the deuterium atoms in the products d- 13 and d- 26 are found in the β-positions to the oxygen atom of the furan ring (schemes 3 and 5). It is suggested that initially a [3s, 3s]-sigmatropic rearrangement of the aryl propargyl ethers to the 6-allenyl-6-halogeno-cyclohexa-2, 4-dien-1-ones (e.g. a ) occurs and that from these the isolated products are formed via radical pathways (scheme 6). Under neutral conditions aryl propargyl ethers containing a free ortho-position give on heating benzopyran derivatives [2]. When this thermal reaction is carried out in sulfolane in the presence of powdered potassium carbonate, 2-methyl-benzofuran derivatives are formed (table 2). This leads to the possibility of preparing, depending on the conditions, either benzopyran or benzofuran derivatives by the Claisen rearrangement of aryl propargyl ethers. The mechanism for the formation of the benzofurans is given in scheme 9.     

Die Cope-Umlagerung als Prinzip einer repetierbaren Ringerweiterung

The Cope Rearrangement, a Reaction for Repeatable Ring Expansions Starting with the unsaturated β-ketoesters of type I, a vinyl group is introduced into the β-position by 1,4-addition of vinyl magnesium chloride to give II (Scheme 3). Treatment of the β-ketoester II with phenyl vinyl sulfoxide in the presence of sodium hydride yields the sulfoxides III, which on thermolysis lead to the α, β-divinyl ketoesters of type IV via elimination of sulfinic acid (Scheme 3). The Cope-System IV undergoes rearrangement to V, which is again an unsaturated β-ketoester. The latter is suitable for a further ring expansion sequence. These reaction steps were carried out with the nine-, twelve- and fifteen-membered ketoesters 32, 33 and 34 , as well as with the open-chain compound 35 (Table 1). With the cyclohexane derivative 31 , ring expansion could not be achieved with the described sequence.     

Aromatization of 3,4-dihydro-β-carboline-3-qarboxylic acid and its derivatives through a carbanion intermediate : mechanistic study and use in chemical synthesis

3,4-dlhydro-β-carboline-3-carboxylic acid , its esters and amide derivatives (AH₂) undergo complete aromatization into corresponding β-carboline derivatives (A) by basic treatment under mild conditions. This, together with the easy obtention of 3,4-dihydro-β-carboline from the parent N^αformyltryptophan derivatives constitutes an attractive possibility to obtain complex molecules containing the β-carboline ring. The mechanism of the reaction was investigated by polarography, U.V.spectrometry and polarimetry. In alcaline media, (AH₂) undergoes two successive equilibria : the first yielding a C₃ carbanion occurs with suppression of the chirality while the second yields a thermodynamically preferred C₄ carbanion which undergoes aromatization through an oxidative pathway (K'_a = 2×10^-14 at 45°C).     

Stereoselektive Synthese von 2′-O-(2-Methoxyethyl)ribonucleosiden: Nachbargruppenbeteiligung der Methoxyethoxy-Gruppe bei der Ribosylierung von Heterocyclen

Stereoselective Synthesis of 2′-O-(2-Methoxythyl)ribonucleosides: Neighboring-Group Participation of the Methoxythoxy Group in the Ribosylation Step A new access to 2′-O-(2-methoxyethyl)ribonucleosides, building blocks for second-generation antisense oligonucleotides, is presented. The influence of various reaction parameters on the coupling reaction of 2-O-(2-methoxyethyl)-D -ribose derivatives with heteroaromatic bases as the key step was investigated, and reaction conditions were optimized with regard to formation of the desired β-D -anomers. With Sn²⁺ salts as promotors in polar solvents, these β-D -anomers were formed with a high degree of steroselectivity.     

BINOL-phosphoric acid catalyzed asymmetric Mannich addition of β-ketoesters to indolenines generated in situ by DDQ

An asymmetric Mannich addition of β-ketoesters to indolenines that were generated in situ from 3-indolinone-2-carboxylates by DDQ has been developed using a catalytic amount of chiral BINOL-phosphoric acid. The corresponding chiral 3-indolinone-2-carboxylate derivatives were obtained in good yields with excellent ee (up to 99%). This is the first report on the enantioselective addition of β-ketoesters to indolenines using a chiral Brønsted acid.     

Silica Sulfuric Acid: An Efficient,Reusable, Heterogeneous Catalyst for the One-Pot,Five-Component Synthesis of Highly Functionalized Piperidine Derivatives

A series of highly functionalized piperidine derivatives was synthesized through one-pot, five-component reaction of aldehydes, amines, and β-ketoesters. Silica sulfuric acid efficiently catalyzes the reaction to afford the corresponding piperidine derivatives in good yields. As a representative example, heating of 4-methylaninle, 4-fluorobezaldehyde, and methyl-acetoacetate in methanol in the presence of silica sulfuric acid furnished the corresponding ethyl 2,6-bis(4-fluorophenyl)-1-p-tolyl-4-(p-tolylamino)-1,2,5,6-tetrahydropyridine-3-carboxylate in excellent yield (85%). Most of the synthesized compounds were screened in vitro for their antibacterial and antifungal activities. Most of compounds showed significant antibacterial activity.     

Bakers’ yeast catalyzed synthesis of polyhydroquinoline derivatives via an unsymmetrical Hantzsch reaction

Bakers’ yeast efficiently catalyzes the unsymmetrical Hantzsch reaction through a four-component coupling of aldehydes, β-ketoesters, dimedone and ammonium acetate to form polyhydroquinoline derivatives in good to excellent yields.     

Saturated heterocycles. 242. Synthesis of 2-substituted-6-(6′,7′-dimethoxy-3′,4′-dihydro-1′-isoquinolyl)-5,6,7,8-tetrahydro- quinazolin-4(3H)-one Derivatives

In the reactions of the recently synthesized β-ketoesters 1-[(3′-methoxycarbonyl- and 1-[(3′-ethoxycarbonyl-4′-oxo)-1′-cyclohexyl]-3,4-dihydroisoquinoline 4, 5 with amidines or cyclic guanidines, a number of 2-substituted-6-(6′,7′-dimethoxy-3′,4′-dihydro-1′-isoquinolyl)-5,6,7,8-tetrahydroquinazolin-4(3H)-one derivatives 6–8 were prepared. The new compounds possess various pharmacological actions.