Formation of 1,2,4-dioxazolidines by electron-transfer photooxygenation of aziridines

DCA-sensitized photooxygenation of $\text{cis}$- and $\text{trans}$-2,3-diphenylaziridine in acetonitrile yields exclusively $\text{cis}$-3,5-diphenyl-1,2,4-dioxazolidine. Photooxygenation of N-alkyl- substituted 2,3-diphenylaziridines provides both isomers of the peroxide. The $\text{cis}$$\text{trans}$ ratio of isomers decreases with increasing size of the group on nitrogen. These stereochemical results provide support for a proposed mechanism involving addition of singlet oxygen to intermediate azomethine ylides.     

Stereoisomerism in the representative tetracyclic dispiro ozonide derived from (methylene)dicyclohexanone with the 1,5-diketo arrangement

The conditions and reasons for the stereoselective transformation of the rac form of 2,2′-(methylene)-dicyclohexanone into the meso- or rac-diastereomer of tetracyclic dispiro ozonide (1,2,4-trioxolane) in the reaction with 30% aqueous H₂O₂ in the presence of acid have been determined. A mechanism for the stereoisomerization of ozonides was proposed, and the stereochemistry of diastereomeric ozonides was established by NMR data.     

Photo-oxygenation of 1,2-diarylcyclopropanes via electron transfer

The photo-oxygenation of 1,2-diarylcyclopropanes bearing electron-donating substituents in the presence of 9,10-dicyanoanthracene (DCA) in acetonitrile affords trans- and cis-3,5-diaryl-1,2-dioxolanes in excellent yields. The DCA-sensitized photo-oxygenation of less electron-rich 1,2-diarylcyclopropanes gives various oxidation products in low yields. These photoreactions are greatly accelerated by the addition of certain aromatic hydrocarbons and metal salts, and are completely quenched by the addition of triethylamine and 1,4-diazabicyclo[2.2.2]octane. No photo-oxygenation takes place in non-polar solvents. The electron transfer mechanism is proposed for the photo-oxygenations, in which the cation radicals of 1,2- diarylcyclopropanes are involved as chain carriers.     

Reaction of arylamidoximes with dimethyl acetylenedicarboxylate and diethyl chlorofumarate. Stereochemistry of the adducts and the derived 1,2,4-oxadiazines

It was shown that the addition of benzamidoxime to dimethyl acetylenedicarboxylate was predominantly cis-oid in methanol or acetonitrile solution and mainly trans-oid when benzene was the solvent. The stereochemistry of the cis-oid ( 4a ) and trans-oid ( 5 ) adducts was deduced by transformation into the oxadia-zinones ( 7a and 8a ) which, upon hydrolysis and subsequent reaction with acetic anhydride, gave the furo-[2,3-c]-1,2,4-oxadiazine ( 9 ) and the symmetrical anhydride ( 10 ), respectively. The reaction of diethyl chlorofumarate with the sodium salt of benzamidoxime produced the oxadiazinone ( 8c ).     

Stereochemical effects in the chemical ionization mass spectra of cyclic diols

The chemical ionization mass spectra of configurational isomers of many cyclic diols give substantial differences which are characteristic of their stereochemistry. For the cis-isomer of 1,3- and 1,4-cyclohexanediols, formation of a stable intramolecular proton bridge involving the OH groups gives rise to dominant MH⁺ peaks, suppressing the (M-H)⁺ peaks found in the spectra of the trans-isomers and monoalcohols. The stability of the proton bridge in cis-1,3-cyclohexanediol structures is decreased by a sterically interfering cis-5-methyl substituent, but increased by a cis-5-OH group due to additional proton solvation. cis-Stereochemistry also gives increased formation of the dimeric M₂H⁺ ions, but decreased formation of trimers, at higher diol concentrations, for the 1,3- and 1,4-diols. The similarity of the CI spectra of cis- and trans-1,2-cyclohexanediol are explicable in terms of the similarities of the most stable proton-bridged conformers; the reduced ring flexibility in cis- and trans-1,2-cyclopentanediols makes such similar structures unfavorable, as shown by the substantial differences between their CI spectra. The substantial, but expected, variations in behavior with temperature and reagent gas are useful for maximizing stereochemical effects on CI spectra; conditions of lowest energy are usually, but not always, the most useful.     

Comparative studies for selective deprotection of the N-arylideneamino moiety from heterocyclic amides: kinetic and theoretical studies. Part 2

4-Benzylideneamino-1,2,4-triazine-3,5(2H,4H)-diones (2-5), 6-styryl-1,2,4-triazine-3,5(2H,4H)-dione (6), and 6-styryl-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one (7) were synthesized and pyrolyzed in the gas phase. The kinetic effect of changing the substituent on the triazine ring from hydrogen to methyl, phenyl, and styryl was measured. Analyses of the pyrolyzates of 2-5 showed the elimination products to be benzonitrile and the triazine fragment, while the pyrolyzates of 6 and 7 reveal the formation of cis- and trans-cinnamonitriles. Theoretical study of the pyrolysis reactions of 2-5 using an ab initio SCF method was investigated.     

The di-π-methane rearrangement : The effect of 1,4-diene structure and conformation on the reaction efficiency and stereochemistry

The photochemistry of the stereoisomeric 1,3-dimethyl-3(2-phenylethenyl)cyclohexenes has been explored Direct irradiation of the cis- and trans-β-styrylcyclohexenes leads to di-π-methane rearrangement, producing the endo- and exo-3,7-dimethyl-8-phenybicyclo[5.1.0]oct-2-enes, and cis -trans isomerization, interconverting the 1,4-diene containing substrates. Triplet sensitized photolysis of both substituted cyclohexenes leads exclusively to cis-trans isomerization. Results from low conversion direct irradiations of the cis- and trans-β-styrylcyclohexenes indicate that the singlet rearrangements are stereospecific, and lead to formation of the 8-exo and 8-endo-phenylbicyclic octenes, respectively. The relationship between di-π-methane structure and triplet reaction efficiency, and the effect of conformation on the rearrangement stereochemistry are discussed.     

Reactivity difference between diphosgene and phosgene in reaction with (2,3-anti)-3-amino-1,2-diols

In reactions of (2,3-anti)-3-amino-1,2-diols with diphosgene and phosgene and their conversion into 1,3-oxazolidin-2-ones, some differences in the stereochemistry of the reactions have been found with these two reagents. The reactions with phosgene afforded the expected cis-oxazolidinones, and in the reaction with diphosgene under the same reaction conditions, the trans-oxazolidinones were also obtained.     

Benzyne-induced ring opening reaction of thiiranes. Efficient synthesis of phenyl vinyl sulfides

A series of thiiranes react with benzyne to provide an efficient synthesis of phenyl vinyl sulfides. The reaction is stereospecific, thus producing cis-(phenylthio)-stilbene from cis-2,3-diphenylthiirane and trans-(phenylthio)stilbene from trans-2,3-diphenylthiirane.     

The balance of steric and conjugative effects in the opening of arylsubstituted oxiranes. Stereochemistry of the ring opening of 1-(1′-naphthyl)-1,2-epoxycyclohexane

The steric course of the ring opening of 1-(1′-naphthyl)-1,2-epoxycyclohexane (3) has been investigated and compared with that of the similar reactions of 1-phenyl-1,2-epoxycyclohexane. Reaction of 3 with KOH in DMSO-H₂O gives small yield of trans diol 4. Reaction of 3 with CCl₃COOH and HCl in low polarity aprotic solvents takes place with complete retention of configuration. However reaction with H₂SO₄ in H₂O is not completely stereospecific and shows a greater tendency than the phenyl substituted epoxide towards cis opening. Explanations of the observed stereochemical results, particularly with respect to the ability of the 1-naphthyl group to stabilize the intermediate carbocation, are discussed.     

Synthesis of 1,2,4-triazole and thiazole analogs of ketoconazole

The synthesis of 1,2,4-triazole and thiazole analogs of ketoconazole is described in which one of the α azole ring carbons is linked to C-2 of the ketal by means of a three methylene tether. Lithiation of 1-methyl-1,2,4-triazole and thiazole and subsequent alkylation with 2-(2,4-dichlorophenyl)-2-(3-iodopropyl)-1,3-dioxolane produced, after an aqueous acidic workup, 2,4-dichlorophenyl 3-[5-(1-methyl-1,2,4-triazolyl) and 2-thiazolyl]propyl ketones, respectively. Ketalization with glycerol furnished the corresponding diastereomeric pairs of cis and trans 1,3- dioxolanes. The reaction of 2,4-dichlorophenyl 3-[5-(1-methyl-1,2,4-triazolyl)]propyl ketone with 3-mercapto-1,2-propanediol produced the corresponding diastereomeric cis and trans hydroxymethyl 1,3-oxathiolanes. The diastereomeric racemates were separated by column chromatography and their stereochemistry established by nOe nmr experiments. Some of these racemic cis ketal alcohols were converted by benzyl bromide to the corresponding benzyl ethers. Several of these racemic cis-ketals were reacted, first with methanesulfonyl chloride, then with 1-acetyl-4-(4-hydroxyphenyl)piperazine, to furnish the title compounds.     

1,2-Disubstituted cyclohexane nucleosides: comparative study for the synthesis of cis and trans adenosine analogues

A new class of adenosine analogues with 1,2-disubstituted carbocycles (with cis and trans stereochemistry) have been synthesized. Construction of the base on the amino group of (±)-cis-(2-aminocyclohexyl)methanol was more efficient than the Mitsunobu condensation between the purine base and protected (±)-trans-(2-hydroxymethyl)cyclohexanol. The latter strategy gave the final compound with cis stereochemistry in a short number of steps with the overall yield depending on the nature of the protecting group on the hydroxymethyl group of the diol. However, Mitsunobu condensation between a purine base and the protected (±)-cis-(2-hydroxymethyl)cyclohexanol is not an ideal method to obtain trans purine derivatives because the elimination reaction is faster than the substitution reaction.     

Syntheses and reactions of terpene β-hydroxyselenides and β-hydroxydiselenides

A convenient method for the synthesis of optically active trans-hydroxyselenides and trans-hydroxydiselenides from the bicyclic terpene group based on the reactions of sodium selenide or sodium diselenide with cis- and trans-(+)-3-carane, trans-(+)-2-carane and (?)-β-pinane epoxides is described. The corresponding cis-hydroxy and cis-methoxydiselenides were obtained in the reaction of sodium diselenide with β-hydroxy- and β-methoxytosylates. The influence of a hydroxy group at the β-position on the diastereomeric ratio of the products of the asymmetric methoxyselenenylation of styrene has been established by composition of the products, crystal structure analyses, and theoretical calculations using a DFT method on the B3LYP level (6-311G(d)).     

Stereoselective synthesis of some cis 2,3- disubstituted cyclanones : Ring size influence on the stereoselectivity of 2-substituted endocyclic enolates protonation

Conjugate addition of carbanionic reagents formed from aryl-or phenyl-thioacetonitriles 1a–1c and 2 to 2-methyl and 2-phenyl 2-cyclohexenone or 2-methyl 2-cyclopentenone, followed by acidic quench, under kinetic control, leads to different ratios of cis and trans 2,3-disubstituted cyclanones according to ring size. From 2-methyl and 2-phenyl 2-cyclohexenone, the cis isomer is highly predominant (85 to 98%). From 2-methyl 2-cyclopentenone a cis/trans mixture is obtained: the cis isomer only predominates when a bulky reagent (1c) is used (80%); in the other cases a mixture of nearly 1:1 is obtained.     

Trans-cis photoisomerization and photoinduced electron transfer as competitive reactions of 9-etylthiacarbocyanine in binary mixtures

The effect of the composition of the dioxane-water mixture on the ability of 9-ethylthiacarbocyanine to participate in competitive reactions of trans-cis photoisomerization and photoinduced electron transfer was studied. An increase in the dioxane content in the range 0–50 vol % leads to a shift of the equilibrium between the dye dimers and monomers toward the monomers (cis-monomers), which is accompanied by a drop in the yield of the triplet dimer molecules, which appear under the action of a laser flash, and electron-transfer products that are formed via the triplet state of dimers in the presence of methylviologen. With growing the dioxane content in the range 50–80 vol %, a shift of the equilibrium between the cis-and trans-monomers toward the trans-monomers occurs, which is accompanied by an increase in the fluorescence intensity. At the dioxane content above 80 vol %, a further shift of the equilibrium toward the trans-monomers occurs, which is accompanied by a substantial increase in the fluorescence intensity and an appearance under the action of a laser flash of the band of the triplet-triplet absorption of the trans-monomer and the absorption band of the cis-monomer as a result of trans-cis photoisomerization. The trans-monomers in the triplet state participate in the electron-transfer reaction with methylviologen. The intersystem crossing process competes with fluorescence and the trans-cis isomerization reaction, which occurs via the excited singlet state of the trans-monomers.     

New chemistry of zwitterionic peroxides arising by photooxygenation of enol ethers

The rosebengal-sensitized photooxygenation of 2-methoxynorborn-2-ene(1)in acetaldehyde gave cis-1-carboxaldehyde-3-carbomethoxycyclopentane (31%) and the cis and trans-Me derivatives of the cis-fuscd exo-1,2,4-trioxanes arising by addition of a molecule of oxygen and acetaldehyde to 1 at C3 and C2 respectively (13%) Similar photooxygenation of 2-(methoxymethylidene)adamantane in the presence of acetaldehyde, propionaldehyde and pivalaldehyde gave adamantanone (31–42%), and the cis and trans tricylo[3.3.1.1^3,7]decane-2-spiro-6'-[3-alkyl-5-methoxy-1,2,4-trioxanes] in yields of 32–53% Trioxane formation under similar conditions was experienced for 1,1-di-t-butyl-2-methoxyethene and 2-(methylmercaptomethylidene) adamantane. The results are discussed in terms of an intermediate zwitterionic peroxide which can either close directly to a 1,2-dioxetane or, if aldehyde is present, condense across the CO function giving the 1,2,4-trioxane.     

Identification of the addition products formed in the chlorination of benzofuran

The cis and trans isomers of 2,3-dichloro-2,3-dihydrohenzofuran have been prepared and their reactions studied in the presence and in the absence of bases. Some data on the influence of the experimental conditions on the stereochemical course of the reaction are also reported.     

The synthesis of (−)-cis- and (−)-trans-crobarbatic acid

The synthesis of both cis- and trans-crobarbatic acid is reported. The five-step sequence proceeds in high yield and with control of both relative and absolute stereochemistry. The key step in the synthesis is the Birch reductive alkylation of a chiral furoic acid which sets the absolute stereochemistry of the products. The stereochemistry of the compounds described was proven unambiguously by X-ray crystallography on one synthetic intermediate and on trans-crobarbatic acid.     

α-Oxides in reactions with N-H acids of the heterocyclic series

The reaction of epoxides with 3-nitro-5-bromo-1,2,4-triazole gave a series of 1-(β-hydroxyalkyl)-3-nitro-5-bromo-1,2,4-triazoles, which, under the influence of bases, undergo intramolecular cyclization with HBr elimination to give an ew heterocyclic system — 2-nitro-5,6-dihydrooxazolo[2,3-e]-1,2,4-triazole.     

Conjugate addition of lithiated Schöllkopf's bislactim ether to 1E,3E-butadienylphosphonates: Stereocontrolled access to 2,3-anti-4E 2-amino-6-phosphono-4-hexenoic acid derivatives

Face-selective 1,6-addition of lithiated Schöllkopf's bislactime ether 5 to 4-substituted, 1,4- or 3,4-disubstituted 1E,3E-butadienylphosphonates6a-d allows a direct and stereocontrolled access to semi-rigid AP6 analogues, the 2,3-anti-4E 2-amino-6-phosphono-4-hexenoic acid derivatives 4a-c. The relative stereochemistry was assigned from a NMR study of the cyclic derivative 12c. Ten-membered trans-fused chair-boat-like transition states are invoked to rationalize the stereochemical outcome of the addition.