Heterodiene synthesis

Both 1,4,-cycloaddition with the formation of a 1,4-dihydro-1,2,4-triazene derivative and electrophilic addition of acetyldicarboxylic acid ester to the secondary nitrogen atom occur during the reaction of acetylenedicarboxylic acid ester with 1,5-diphenyl-3-methyl-3-methylformazan. In the case of l,5.diphenylformazan, the reaction proceeds only in the second direction.See [3] for Communication II.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1704–1705, December, 1970.     

Heterodiene synthesis

2-Phenyl-4,6-diaryl-1,2-dihydro-sym-triazines react with hexafluoro-2-butyne as a dienophile to give 4,5-bis(trifluoromethyl)-2,6-diarylpyrimidines.See [1] for communication V.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 122–123, January, 1977.     

Heterodiene synthesis

Transamination occurs in the reaction of amidines of benzoic and trichloro- and trifluoroacetic acids with azomethines obtained from aniline and various aromatic aldehydes; two molecules of the resulting benzylideneamidines react to give 1,2-dihydro-sym-triazines via the Diels-Alder scheme with the liberation of imino aldehydes.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 281–283, February, 1973.See [1] for communication IV.     

Heterodiene syntheses—XIV: The reaction of 3-oxindolideneacetophenones with ethyl vinylether

Ethyl vinylether reacts with 3-oxindolideneacetophenones. In addition to some 2,3-dihydropyran[2,3-b]indoles, obtained by 1,4-cycloaddition, previously unknown 3-(3-oxindolyl)dihydrofurans whose origin may involve a dipolar intermediate were isolated. Rationalization of the mechanism is proposed and the approach in terms of frontier orbitals is discussed.     

Heterodiene Synthesis. I. Reaction of 5-Arylidenerhodanine Derivatives with 1-Morpholinocyclohexene Enamine

Cycloaddition of 5-arylidenerhodanine derivatives l_a-d as α, β unsaturated carbonyl system attached to a heterocyclic nucleus with enamine E as an electron rich dienophile lead to 3,4-dihydro-2H-pyrans 2_a-d. The results differed depending on the nature of the substituent of the arylidene group. The introduction of an electron-withdrawing group in the p-position of arylidene moiety should increase the facility of the reaction.     

Heterodiene synthesis—XI : A study of the isomerization of tetrahydropyran[2′,3′:2,3] 2,3-dihydropyran[6,5-c] pyrazoles

The stereoisomers (1–4) of the tetrahydropyran[2′,3′:2,3] 2,3-dihydropyran[6,5-c] pyrazole system equilibrate in deuterated trifluoroacetic acid at 35°.The mechanism which causes incorporation of deuterium in the 4a-position is discussed.The isomers distribution is rationalized in terms of steric and electronic interactions, and the energy values for the interaction between the phenyl group in 5 and the substituent in position 6 on the pyrazole ring are given.     

Heterodiene synthesis. Synthesis of fused thiopyrano [2,3-d]thiazole,Benzopyrano[3′,4′:4,5]thiopyrano[2,3-d]thiazole and thiazolo[3,4-c]triazine derivative

5-Salicylidenethiazolidine-2,4-dithione ( 1 ) reacts with acrylonitrile, N-phenylmaleimide and dimethyl acet-ylenedicarboxylate to afford the fused thiopyrano[2,3-d]thiazolidinethione derivatives 2, 4 and 6 , respectively. The salicylidene derivative 1 reacts with ethyl acrylate and malononitrile to afford the fused [1]benzopyrano[3′,4′:4,5]thiopyrano[2,3-d]thiazoles 3 and 9 , respectively. 4-Phenylhydrazono-2-thiazolidinethione ( 11 ) reacts with ethyl bromoacetate and/or phenacyl bromide to yield the fused thiazolo[3,4-c]triazines 13 and 14.     

Heterodiene syntheses—XIX: Correlation of the kinetic data with lumo energies in the reaction between 1-aryl-4-benzylidene-5-pyrazolones and isopropyl vinyl ether

The kinetics of the reaction between 1-p-substituted phenyl-4-benzylidene-5-pyrazolones and isopropyl vinyl ether have been studied by quantitative spectroscopic analysis and liquid chromatography. The rate increases with the electron attracting character of the substituents and a correlation is obtained with σ- constants. The polarographic one-electron half-wave reduction potentials E^red_{$\text{1}\text{2}$}, which represent an experimental measure for the relative energy of the lowest unoccupied molecular orbital (LUMO), were measured. Good correlations were obtained between these and the kinetic data, thus demonstrating the frontier-controlled character of the cycloaddition and the dominant interaction between the LUMO of the pyrazolone and the highest occupied molecular orbital (HOMO) of the vinyl ether.     

Heterodiene syntheses—XXIV: Changes in the reactivity of 2-oxoindolin-3-ylidene derivatives with ethylvinylether induced by electron-withdrawing groups. The importance of the lumo coefficients

Ethylvinylether reacts in acetonitrile with 1 - acetyl - 2 - oxoindolin - 3 - ylidene derivatives β,β -disubstituted with electron-withdrawing substituents. When the β-substituents act by inductive effect alone, a regiospecific β-attack² occurred giving rise, through a 1,4 - cycloaddition, to 2,3 - dihydropyran[2,3-b]indoles. As a by product Michael adduct can be obtained. When the β-substituent act by conjugative effect also, a regiospecific α-attack² occurred giving rise to spiro - dihydropyrane or - cyclobutane - 2 - oxoindolines depending on the nature of the substituents.In a less polar solvent, the latter ones are formed together with the adduct arising from the regioisomeric β-attack.The overall reactivity can be rationalized in terms of LUMO coefficients of the hetcrodiene and of different stabilization offered by the solvent to the various reaction pathways.     

Heterodiene syntheses—XIII: The stereochemical consequences of electronic and steric interactions in the transition state of the cycloaddition between 4-arylidene-5-pyrazolones and vinylethers

The competition between exo and endo transition states in the cycloaddition of 4-arylidene-5-pyrazolones and vinylethers is rationalized in terms of steric and electronic interactions.The steric interactions depend mainly upon the requirements of the substituent in position 3 of the starting pyrazolone.The electronic factors are rationalized in terms of secondary non-bonding interactions between the HOMO of the vinylether which acts as donor and the LUMO of the pyrazolone which acts as acceptor.An E configuration of the pyrazolone is suggested as “reacting” species.     

Heterodiene syntheses—XII : The conformational analysis of cis and trans 2-alkoxy-4-phenyl-2,3-dihydropyran[2,3-c] pyrazoles: Steric interactions and the anomeric effect

The conformational equilibria of a homogeneous series of cis and trans 2-alkoxy-4-phenyl-2,3-dihydropyran[2,3-c] pyrazoles have been investigated by a graphical method, and the preferences are rationalized in terms of steric interactions between the 4 and 5-substituents and of the anomeric effect.The anomeric interaction depends upon the nature of the alkoxy group and the conformational free-energy differences correlate with the steric parameters E_s.     

Heterodiene syntheses—IX : Polar character of the thermal rearrangement of the adducts from 3-oxindolideneacetophenones and enamines

The cyclic adducts resulting from the reaction between N-substituted 3-oxindolideneacetophenones and enamines undergo thermal rearrangement in CDCl₃ at 35°. If the adducts originate from the β-dimethyl substituted enamine, they revert to the starting materials. In contrast the β-monomethyl substituted adducts are transformed into Michael-type enamines. Both classes of adducts react with tetracyanoethylene to give spirocyclohexane oxindoles. All the reported reactions seem to occur through the same intermediate with a zwitterionic character.     

Heterodiene syntheses—X : Reaction of arylidene-pyrazolones and -isoxazolones with dihydropyran: Nature of the transition state

Dihydropyran reacts easily with the α, β-unsaturated carbonyl system of heterocyclic rings (pyrazoles or isoxazoles) in accordance with a 1,4-cycloaddition.     

Recent developments in oligosaccharide synthesis: tactics,solid-phase synthesis and library synthesis

Oligosaccharides, commonly found on the cell surfaces, are deeply involved in a variety of important biological functions, yet demanding difficulties synthesizing such structures limit the investigation of their functions. Technologies to chemically synthesize these oligosaccharides have dramatically advanced during the last two decades mainly due to the introduction of good anomeric leaving groups. In addition, tactical analyses have been addressed to enhance the overall efficiency of oligosaccharide synthesis. Based on the advancement of solution-phase chemistry, solid-phase technologies are being investigated in connection with the current trend of combinatorial chemistry and high throughput screening. This review summarizes the necessary solution-phase methodologies, the status of solid-phase synthesis of oligosaccharides, and combinatorial synthesis of oligosaccharide libraries.     

Asymmetric synthesis of cyclobutanones: synthesis of cyclobut-G

A simple, efficient, and stereoselective approach has been developed for obtaining chiral cis- and trans-disubstituted cyclobutanones from readily available alkyl- and functionalized alkyl-substituted enol ethers. The usefulness of these cyclobutanones is illustrated by an enantioselective synthesis of cyclobut-G (Lobucavir).     

Formal synthesis of nitidine through palladium-catalyzed isocoumarin synthesis

The isoquinolone intermediate 9 for the synthesis of nitidine was synthesized through palladium-catalyzed formation of isocoumarin 7 from o-styrylbenzoic acid derivative 5, which was prepared from palladium-catalyzed coupling reactions of aryl iodide 1 and 2 with vinylsilane.     

Benzothiazines in synthesis. Formal synthesis of erogorgiaene

A benzothiazine, readily available in enantiomerically pure form via a completely selective, intramolecular addition of a sulfoximine-stabilized carbanion to an α,β-unsaturated ester, could be converted to a precursor to erogorgiaene in good overall yield.     

Biology-oriented synthesis

Which compound classes are best suited as probes and tools for chemical biology research and as inspiration for medicinal chemistry programs? Chemical space is enormously large and cannot be exploited conclusively by means of synthesis efforts. Methods are required that allow one to identify and map the biologically relevant subspaces of vast chemical space, and serve as hypothesis‐generating tools for inspiring synthesis programs. Biology‐oriented synthesis builds on structural conservatism in the evolution of proteins and natural products. It employs a hierarchical classification of bioactive compounds according to structural relationships and type of bioactivity, and selects the scaffolds of bioactive molecule classes as starting points for the synthesis of compound collections with focused diversity. Navigation in chemical space is facilitated by Scaffold Hunter, an intuitively accessible and highly interactive software. Small molecules synthesized according to BIOS are enriched in bioactivity. They facilitate the analysis of complex biological phenomena by means of acute perturbation and may serve as novel starting points to inspire drug discovery programs.