Heterodiamantane und strukturell verwandte Verbindungen II. Pentacyclische Diäther der C10-Reihe: 5,12-Dioxapentacyclo-[6.4.0.02,6.04,9]dodecan und 4,12-Dioxapentacyclo[6.3.1.02,7.03,10.05,9]- dodecan

In connection with studies on heterodiamantanes and structurally related compounds the two novel pentacyclic diethers 9 and 10 were prepared starting from the photo-dimer 8 of cyclopentadienone. All three compounds have as common features a central carbocyclic 6membered ring with four axial alkyl substituents and two oxygen function in 1,4-position. The diether 9 was obtained on the one hand from the intermediate tetracyclic unsaturated alcohol 23 by intramolecular addition, catalyzed either by acid or base (scheme 3), and on the other hand from the tetracyclic diol 32 or the dibromoketones 34 (via 38 ) and 35 (via 39 ) by intramolecular substitution (schemes 4 and 5). The synthesis of the isomeric diether 10 was achieved by intramolecular substitution of the tetracyclic diol 33 (scheme 4). Diether 9 is thermodynamically more stable than 10 . The latter was easily isomerized to the former on treatment with concentrated sulfuric acid in benzene.     

Synthesis in the diazasteroid group. V. Synthesis of the 9,14-diazasteroid system

By the condensation reaction of 2-chloroquinoline (X) and ethyl 2-pyrrolidineacetate (II), 2-[1′-(2′-carboethoxymethyl)pyrrolidyl]quinoline (XI) was prepared. Compound XI was converted to the quarternary base (XIII) having a 9,14-diazasteroid skeleton by the reduction of the ester to the corresponding alcohol followed by the quaternarization via tosylation. Compound XIII was reduced with sodium borohydride to 9,14-diazagona-1,3,5(10)-triene (III), which is suggested to have the trans-anti-trans conformation.     

ELECTROPHILIC CLEAVAGE OF SULFENATE ESTERS. I. POSSIBLE BIOLOGICAL IMPLICATIONS

Abstract

Base-assisted electrophilic cleavage of sulfenate esters was studied with reference to possible biological models. It is suggested that sulfenate esters (RSOR') may serve as intermediates in oxidations involving alcohol dehydrogenases. Models for the biological oxidation of alcohols via sulfenate ester intermediates are presented. The lipoic acid catalyzed dehydrogenation step in the actions of α-ketoacid oxidases (e.g., pyruvic acid dehydrogenase and α-keto glutarate dehydrogenase) is also explained in terms of a possible sulfenate ester intermediate.

In the interaction of alcohols and amines, with membrane proteins, the possibility of reversible formation of sulfenate esters and of sulfenamide formation is suggested. Experimental support is given for the formation of carbonyl compounds, from alcohols via sulfenate esters and subsequent electrophilic attack by N-iodosuccinimide on the esters. Such reactions of sulfenyl esters open virtually unexplored areas of chemistry and of the related biological implications. Methyl fluorosulfate (‘magic methyl’) in presence of base is also effective for the cleavage reaction.     

The synthesis of 6-C-substituted 9-methoxymethylpurine derivatives

6-Cyanomethylene ( 2 ), which was prepared via 1 by substitution with malononitrile, has been catalytically hydrogenated to the α-(aminomethylene)-9-(methoxymethyl)-9H-purine-6-acetonitrile ( 3 ) in good yield using N,N-dimethylformamide-benzene as solvent over Pd-C under medium pressure. Intermediate 3 was derived to aldehyde 5 by hydrolysis with acid or base. Substitution of 3 with amines gave the corresponding alkylamines 6 and 7 . Reaction of 3 with hydrazine and acetamidine hydrochloride gave pyrazole derivative 8 and pyrimidine derivative 9 , respectively.     

Thiohydantoin Nucleosides. Synthesis Approaches

Summary. Several thiohydantoin N-nucleosides and their S-glycosides were prepared via different approaches which involved the direct glycosylation of the free thiohydantoin bases or their silylated derivatives with the corresponding sugar moieties in the presence of base or Lewis acid. Deprotection was carried out in acidic or basic medium. The site of N- and/or S-glycosylation was determined by NMR and UV measurements. In similar manner, hydantoin nucleosides were prepared.Present address: Riaydh Teachers College, P.O. Box 4341, Riaydh 11491, Saudi ArabiaPresent address: EuroMed-Konstanz, P.O. Box 100552, D-78405 Konstanz, Germany     

Palladium-Catalyzed Carbonyl Allylation of Aldehydes with Allylic Phosphates: Synthesis of Homoallylic Alcohols

Allylation of aldehydes by reaction allylic phosphates with diethylzinc in the presence of Pd(PPh₃)₄ afforded homoallylic alcohol via nucleophilic allylzinc species.     

On the Claisen Rearrangement of Allyl Ethyl Ketene Acetals Generated in situ via Benzeneselenenic Acid Eliminiation

Mixed acetals 7 of benzeneseleninylacetaldehyde, prepared by a simple 2-step procedure from mono- and bicyclic allylic alcohols 5 , undergo benzeneselenenic acid elimination to transient ketene acetals 8 which afford γ, δ-unsaturated esters 9 via the ester Claisen rearrangement (Scheme 2). Under the same conditions selenoxide 7h derived from benzyl alcohol 5h is converted back to benzyl alcohol with the concomitant formation of ethylphenylselenoacetate 12 .     

A Simple Procedure for the Preparation of 4-(α-Mercaptobenzyl)Phenoxyacetic Acid,A Thiol Linker Unit Used in Solid Phase Synthesis of Peptide-α-Thioacids

A convenient procedure for the preparation of the title compound via direct thionation of its alcohol precursor by Lawesson's reagent is described.     

Mechanisms of Diazo Coupling Reactions. Part XXX. N-Diazo coupling of p-chloroaniline in acetonitrile: Rate-Limiting proton transfer

The N-diazo coupling of p-chloroaniline with p-chlorobenzenediazonium tetrafluoroborate in acetonitrile at 30° shows non-linear base catalysis by water. The results are interpreted in terms of the S_E2 mechanism with rate-limiting proton loss at low base concentration; it is postulated, moreover that the reaction proceeds via transition states in which varying degrees of H-bonding from the amine and the intermediate ω-complex to different water species influence the initial step and the base catalysis.     

Novel transformations of two kinds of chlorinated photo [2 + 2] cycloadducts of 2-pyrone-5-carboxylate

Novel reactions of 7,7-dichloro- and 7,7,8-trichloro-3-oxo-2-oxabicyclo[4.2.0]oct-4-ene-6-carboxylates 5 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in alcohol gave pyrano[4,3-b]pyran-2,5-diones 8 via (Z)-(2H-pyran-2-on-3-yl)butenoates 7. On the other hand, the same treatment of 7,7,8-trichloro-2-oxo-3-oxabicyclo-[4.2.0]oct-4-ene-5-carboxylate 6b afforded 2-oxo-3-oxabicyclo[4.2.0]oct-4,7-diene-5-carboxylate 14 via cyclobutene formation and S_N2′ displacement by attack of the alkoxy anion.     

Einfache Synthese von 6-[4-Methyl-3-cyclohexen-1-yl]-hept-5-en-2-on,einer Vorstufe für α-Bisabolen und dessen Isopropenyl-Isomers. Terpene und Terpen-Derivate, 10. Mitteilung

Simple Synthesis of 6-[4-Methyl-3-cyclohexen-1-yl]-5-hepten-2-on, a Precursor of α-Bisabolene and Its Isopropenyl Isomer The alcohol 14 reacts with vinyl resp isopropenyl ether by Claisen rearrangement to give the aldehyde 16/17 resp. the ketone 3/4. Contrary to other reports this separable (E/Z)-mixture also occurs as a result of the synthesis following the pathway 7 → 8/9 → 10/11 → 12/13 (see also [2]). The bisabolene isomers 5 resp. 6 are obtained by reaction of 3 resp. 4 with methylidene triphenyl phosphorane. A mixture of 1 and 5. however, is formed from 3 via the alcohol 18 and its acetate 19. Likewise 4 reacts via 20 and 21 to give a (2/6) -mixture.     

Ruthenium-Catalyzed Allylic Substitution of Allylic Cyclic Carbonates

Allylic substitution of allylic cyclic carbonates with PhSH or PhOH in the presence of CpRu(PPh₃₎₂Cl (5 mol %) afforded (E)-allylic alcohol and erythro-β-hydroxy thiophenoxide or phenoxide respectively, via external attack of nucleophiles to π-allyl ruthenium complex.     

Synthesis of Carbo- and Heterocyclic Cycloprop[f]indenes via cycloaddition of dienes to cyclopropenes

The heterocyclic cycloprop[f]indene 19 was synthesized via cycloaddition of diene 10 to the cyclopropene 11a and subsequent base-induced aromatization. While 19 is isolable, although very short-lived, the oxa analogue 18 decomposed under the conditions required for its preparation. The difluoro derivatives 14 and 15 , in which the heterocyclic moiety is saturated, are accessible by the cycloaddition approach, but the corresponding dichlorides are again not isolable. Cycloprop[f]indenes carrying substituents at C(4) have been obtained via cycloaddition of 22b to 1-bromo-2-chlorocyclopropene. The key step of the sequence is a double Curtius degradation of the cycloadduct 23b to the ketone 27a . While aromatization of the alcohol 27b provided the cycloprop[f]indenol 28b , the reaction failed with 27a . Attempts to convert 28b to 1,3-dihydrocycloprop[f]indene ( 25 ) via the methanesulfonate 28d failed.     

Kinetic evidence for the mechanism of liquid-solid phase oxidation of alcohols

Benzyl alcohol oxidation is catalyzed by solid MnFe_1.8Cu_0.15Ru_0.05O₄ in the presence of molecular oxygen. The good compliance of oxidation kinetics with the Michaelis-Menten enzyme kinetic model evidences the oxidative dehydrogenation of benzyl alcohol via a Ru-alkoxide intermediate, which undergoes b-elimination to afford benzaldehyde. This revised version was published online in August 2006 with corrections to the Cover Date.     

Acid-Catalyzed Rearrangements for a Diastereoselective Entry into a New Fused Hexacyclic Heterocycle: (5RS,7aRS,12RS,14aRS,)-4,5,7a,11,12,14,14a-octahydro-5,12-dimethyl-diindolo [1,7-bc: 1′,7′-gh][2,6] naphthyridine

The title compound 1 was obtained in 10.3% overall yield via two acid-catalyzed rearrangements and pyrrolidine formation. Thus, bi-oxindole 6 afforded exclusively the thermodynamically stable cis-diazachrysene 7 which, after allylation, followed by aza-Claisen rearrangement gave alcohol 2 . Pyrolytic ring closure of the latter yielded 1 in highly diastereoselective fashion.     

Zur photochemie des β-pyridinalanilins

The Schiff base, 3-pyridinal aniline was cyclized via photohydration into quinoline-3-carbaldehyde in 20% yield.     

Alternative Synthesis of 2‐Hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one

The 2‐hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one ( 1 ) was synthesized in 42% yield by rearrangement of epoxy ketone 10 on treatment with BF₃⋅Et₂O under anhydrous conditions. Intermediate 10 was available from the known enone 8 , either via direct epoxidation (60% H₂O₂, NaOH, MeOH; yield 50%), or via reduction to the corresponding allylic alcohol 14 (LiAlH₄, THF), followed by epoxidation ([VO(acac)₂], ^tBuOOH) and reoxidation under Swern conditions, in 37% total yield.     

Cobalt(II) schiff base functionalized mesoporous silica as an efficient and recyclable chemoselective acetalization catalyst

Cobalt(II) Schiff base functionalized mesoporous silica was synthesized from covalent attachment via the introduction of Co(OAc)₂ to salicylaldimine functionalized mesoporous silica. The catalyst proved to be chemoselective one for the acetalization of aldehydes to the corresponding acetals in alcohol. The immobilized catalyst can be easily recovered and reused for at least ten reaction cycles without significant loss of its catalytic activity.     

A rhodium‐catalyzed route for oxidative coupling and cyclization of 2‐aminobenzyl alcohol with ketones leading to quinolines

2‐Aminobenzyl alcohol undergoes oxidative cyclization with aryl(alkyl), alkyl(alkyl) and cyclic ketones in dioxane at 80° in the presence of a catalytic amount of RhCl(PPh₃)₃ along with KOH to afford the corresponding quinolines in good yields. The catalytic pathway seems to be proceeded via a sequence involving initial oxidation of 2‐aminobenzyl alcohol to 2‐aminobenzaldehyde by a rhodium catalyst, cross aldol reaction between 2‐aminobenzaldehyde and ketones, and cyclodehydration.     

Probes for a Regulatory Site on the Nicotinic Acetylcholine Receptor-Channel. Synthesis of (±)-7-Debutylperhydrohistrionicotoxin, (±)-2-Depentyl-7-debutylperhydrohistrionicotoxin,and their Analogues

Reaction of glutarimide with pent-4-enylmagnesium bromide, followed by cyclization of intermediate ketoamide, and hydrolysis of the formates 10 and 13 led to the mixture of the hydroxylactams 11 (cis) and 14 (trans) which could be separated via their benzenecarbamates. Reduction of cis-hydroxylactam 11 with LiAlH₄ yielded 2-depentyl-7-debutylperhydrohistrionicotoxin ( 6 ), whereas reduction of trans-isomer 14 gave the epimeric alcohol 9 . cis-Hydroxylactam 11 was converted via thiolactam 17 and the methylthio derivative 18 to ketimine 19 which was reduced with NaBH₄ yielding a mixture of natural 4 and unnatural 7 , analogues of perhydrohistrionicotoxin ( 2 ). Reduction of 4 with H₂ in the presence of Pd/C yielded (±)-7-debutylperhydrohistrionicotoxin ( 5 ).