Synthesis of 1-Acetamido-2-acetyladamantane

The triple bond of 2-ethynyl-2-adamantanol virtually did not hydrolyze under Kucherov reaction conditions in aqueous ethanol and methanol. In aqueous acetic acid arose a mixture of 2-acetyl-2-adamantanol and its acetate. In good yield the 2-acetyl-2-adamantanol was obtained by Kucherov reaction in aqueous THF. This alcohol with acetonitrile under conditions of Ritter's reaction (catalysis with sulfuric acid) afforded a mixture of 1-acetamido-2-acetyl-, 1-acetamido-4-cis- and 1-acetamido-4-trans-acetyladamantanes in 8:1:1 ratio.     

Hydrogenation of 2- tert -butylphenol over Ni catalyst

The hydrogenation of 2-tert-butylphenol was studied in regard to possibilities of influencing selectivity, namely the ratio ofcis- andtrans-isomers of 2-tert-butylcyclohexanol in the final reaction mixture. The hydrogenation reactions were carried out using the catalyst Ni/Al₂O₃. During the hydrogenations, a higher content of thecis-isomer was attained, when simultaneously the final reaction mixture contained 2-tert-butylcyclohexanone. The content of this intermediate, which primarily hydrogenated to thecis-isomer, increased with a decreased pressure and after the addition of acetic acid into the reaction mixture.     

Stereospecific syntheses of all four stereoisomers of 4-fluoroglutamic acid

(+)- -threo-4-Fluoroglutamic acid [(+)-(2S, 4S)-fluoroglutamic acid] has been synthesizedstarting with the natural (−)-4-trans-hydroxy- -proline. Its acetylation at nitrogen followedby esterification with diazomethane afforded methyl 1-acetyl-trans-4-hydroxy- -prolinatewhich was converted to methyl 1-acetyl-cis-4-fluoro- -prolinate by means of diethylaminosulfurtrifluoride (DAST) or 2-chloro-1,1,2-trifluorotriethylamine. The mixture wasoxidized by ruthenium tetroxide to methyl 1-acetyl-cis-4-fluoro- -pyrrolidin-5-one-2-carboxylate,whose acid hydrolysis yielded the title compound. A similar sequence of reactionsconverted cis-4-hydroxy- -proline to (−)- -erythro-4-fluoroglutamic acid [(−)(2R, 4S)-fluoroglutamic acid]. (−)- -threo-4-Fluoroglutamic acid [(−)-(2R, 4R)-floroglutamicacid] was prepared analogously from trans-4-hydroxy- -proline, obtained from its diastereomerby inversion of configuration at carbon 4 of the pyrrolidine ring using thediethyl azodicarboxylate-triphenylphosphine procedure. cis-4-Hydroxy- -proline, necessaryfor the synthesis of (+)- -erythro-4-fluoroglutamic acid [(+)-(2S, 4R)-fluoroglutamicacid], was prepared from trans-4-hydroxy- -proline by benzyloxycarbonylation at thenitrogen, oxidation of the 1-benzyloxycarbonyl-trans-4-hydroxy- -proline to 1-benzyloxy-carbonyl-4-oxo- -proline, its reduction to 1-benzyloxycarbonyl-cis-4-hydroxy- -proline anddeprotection of the latter at the nitrogen. (−)-cis-4-Fluoro- -proline and (+)-trans-4-fluoro- -proline were isolated after the hydrolysis of incompletely oxidized methyl 1-acetyl-cis-4-fluoro- -prolinate and methyl 1-acetyl-trans-4-fluoro- -prolinate, respectively.     

Sterical Hindrances as a Driving Force of Skeleton Rearrangements of Fenchone and Its Oxime in Ritter Reaction

Fenchone (1,3,3-trimethylbicyclo[2.2.1]heptan-2-one) in reaction with acetonitrile in the presence of sulfuric acid (Ritter reaction) due to steric hindrances preventing geminal addition of two nucleophile molecules gives rise to a mixture of 1,2-exo-diacetamido-6-endo,7,7-trimethylbicyclo[2.2.1]heptane, 2-endo6-exo-diacetamido-3,3,6-trimethylbicyclo[2.2.1]heptane, and 2-exo,6-exo-diacetamido-1,3,3-tri- methylbicyclo[2.2.1]heptane in the ratio of 6:4:1. Fenchone oxime under condition of this reaction affords a mixture of stereoisomeric cis- and trans-acetamido-1-methyl-3-(-cyanoisopropyl)cyclopentanes in 2:3 ratio.     

Zur Konfiguration der 2,4,6,8-Tetrabrom-cyclooctan-1,5-dione Reduktion des β-Isomers durch Natrium-borhydrid

Of the two previously described 2,4,6,8-tetrabromo-cyclooctane-1,5-diones, the higher melting β-isomer, mp. 226°, was treated with sodium borohydride to give: (1) by a double reduction and an intramolecular S_N2-reaction two epimeric alcohols, namely the 2-exo-hydroxy- ( 6 ) and 2-endo-hydroxy- ( 7 ) isomers of 3-exo,5-exo,7-endo-tribromo-9-oxa-bicyclo[4.2.1]nonane, and (2) by a single step reduction a hemiketal, 1-hydroxy-2-exo,4-exo,6-endo,8-endo-tetrabromo-9-oxa-bicyclo[3.3.1]nonane ( 8 ). The structures of these three hydroxy-compounds ( 6, 7 and 8 ) were derived from their properties, especially from complete analyses of their NMR.-spectra, which led to deductions of all configurations and conformations. Of special interest is the preferred existence of the 9-oxa-bicyclo[3.3.1]norane derivative 8 in a chair-chair conformation. The derivation of the configurations of the three hydroxy-compounds 6, 7 and 8 is tantamount to establishing the 2,4-cis, 4,6-trans, 6,8-cis-configuration ( 5 ) of the β-isomer of 2,4,6,8-tetrabromocyclooctane-1,5-dione, mp. 226°.     

Palladium(II) and platinum(II) complexes with N-substituted methionines

Summary As an approach to systems containing methionine residues, 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one (HDh, dehydroacetic acid) was treated with L-methionine (MetH) or L-methionine methylester (MetM). By condensation at the acyl group and transfer of the phenolic hydrogen on the nitrogen atom, the related ligands DhMetH and DhMetM, were isolated, and form complexes of formula [MX₂(L)₂](M = Pd or Pt, L = DhMetM, X = Cl, Br or I; L = DhMetH, X = Cl or Br) and [MI₂(DhMetH)] with palladium and platinum dihalides. The reaction of the DhMetK carboxylate with MCl₂ in various media is discussed. Ligands and complexes were characterized by i.r. and n.m.r. (¹H and¹³C) spectroscopy and, in some cases, by thermogravimetric measurements. The ligands behave as monodentate sulphur donors, the 12 complexes showing atrans geometry except for [PtCl₂(DhMetH)₂], which is probably a mixture ofcis andtrans isomers.     

Ultrasound-assisted convenient synthesis of hypolipidemic active natural methoxylated (E)-arylalkenes and arylalkanones

An ultrasound-assisted convenient method was developed for the conversion of toxic methoxylated cis-isomer of arylalkenes into its hypolipidemic active trans-isomer. Treatment of cis-isomer or mixture of all three isomers (1a-1j) with ammonium formate and 10% Pd/C gave arylalkanes (2a-2j), which upon oxidation with DDQ in anhydrous dioxane containing a little amount of silica gel, provided (E)-arylalkenes (3a-3g) in 42-72% yield depending upon the substituents attached at the aryl ring. The same method, upon addition of a few drops of water, provided hypolipidemic active arylalkanones (3h-3j) in 59-65% yield.     

Herstellung von Dihydro-, Tetrahydro- und Hexahydrochelidamsäure-Derivaten

Preparation of dihydro-, tetrahydro- and hexahydro-chelidamic-acid derivatives. Three methods for the preparation of 4-oxo-2,6-piperidine-dicarboxylic acid ( 3 ) and derivatives, required as a synthon for betalaine pigments, were explored. The best method was found to be the catalytic hydrogenation of chclidamic acid ( 1 ) with 5% Rh/Alox in water under 2.7 atm. H₂ for 33 h at 70° and subsequent esterification with methanol which gave 42% of cis, cis-4-hydroxy-2,6-piperidine- ( 7 ) and 10% of 2,6-cis-piperidine-dicarboxylic acid dimethyl ester ( 8 ), readily separable by chromatography. Oxidation of 7 with dimethylsulfoxide and a carbodiimide attached to a polymer afforded 90% of 4-oxo-2,6-cis-piperidine-dicarboxylic acid dimethyl ester ( 19 ). Other methods of oxydizing 7 to 19 were less successful. The electrochemical reduction of 1 followed by esterification with methanol led in a low yield to a mixture of 4-oxo-0-2,6-trans-piperidine-dicarboxylic acid dimethylester ( 24 ), its dimethyl acetal 25 and presumably trans-4-hydroxy-r-2, cis-6-piperidine-dicarboxylic acid dimethyl ester ( 26 ). Reaction of 4-oxo-hepta-2E, 5E-dienoic acid ( 35 ) with aqueous ammonia gave a 98% yield of a 3 : 2 mixture of cis- and trans-ammonium-4-oxo-2, 6-piperidine-dicarboxylate ( 39 and 40 ). The above mentioned catalytic hydrogenation method was also applied to N-ethyl-chelidamic acid ( 16 ) to give a 4:6 mixture of the N-ethyl derivatives 17 and 18 . Furthermore, a number of functional derivatives of 5 , of 19 , of 39 and of 40 were prepared. Oxidation of the hydroxy-diester 7 with dimethylsulfoxide and a carbodiimidc derivative in the presence of trifluoroacetic acid afforded 4-oxo-1,2,3,4-tetrahydro-2, 6-pyridine-dicarboxylic acid dimethyl ester ( 50 ). This ester was also obtained under the same conditions from thc keto-diester 19 .     

Synthesis of (±)-trans-2,5-Dialkylpyrrolidines from the Lukes-Šorm Dilactam: Efficient Preparation of (±)-trans-2-Butyl-5-heptylpyrrolidine and Analogs Present in Ant Venoms

A 7-step synthesis of (±)-trans-2-butyl-5-heptylpyrrolidine ( 14 ) from the Lukes-?orm dilactam 1 was accomplished in 6% overall yield without counting for a reconversion of cis-isomer 13 into trans-isomer 14 which was also accomplished. Reduction of pyrroline 12 , the precursor of 14, with NaBH₄ afforded a 1:1 mixture of cis-isomer 13 and trans-isomer 14 separated by chromatography. Reductive N-methylation of 14 afforded the N-methyl analog 15 , another ant alkaloid. The synthetic route to 14 was extended to a similar synthesis of analogs 23 – 25 and is representative for the synthesis of trans-2,5-diakyl-substituted pyrrolidines. Results on the screening of a few compounds for the effect on vascular permeability are reported.     

Stereochemistry of nitrogenous heterocycles. 71. Isomerization — Equilibration of stereoisomeric ethinylcarbinols epimeric at the carbinol center

Equilibration of stereoisomeric cyclic ethinylcarbinols, epimeric at the carbinol center, was conducted for the first time and it was shown that the equilibrium is shifted toward the equatorial alcohol (at 50C for 2e-methyl-4-hydroxy-4-phenylethinyl-trans-decahydroquinoline, 2e-methyl-4-hydroxy-4-ethinyl-trans-decahydroquinoline, 4-hydroxy-4-ethinyl-trans-decahydroquinoline —(78±1)% equatorial and (22±1)% axial alcohol, for 1,2e,5e-trimethyl-4-ethinylpiperidol-4 (74±1)% equatorial and (26±1)% axial alcohol). The epimerization of stereoisomeric ethinylcarbinols can be used as a method for determination of the configuration of the quaternary carbinol center.See [1] for Communication 70.The data was presented at the VI International IUPAC Conference on Organic Synthesis [2].Translated from Khimi-ya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1072–1076, August, 1991.     

Structures of Ring-Enlargement Products

Crystal structures have been determined of methyl trans-1-hydroxy-6-nitro-3-oxobicyclo[4.4.0]decane-2-carboxylate ( 19 ), cis-3-methyl-6-nitro-2-oxabicyclo[4.4.0]decan-1-ol ( 2 ), cis-7-hydroxy-1-nitrobicyclo[5.4.0]undecan-9-one ( 13 ), and the medium-ring compounds 2-acetyl-4-nitrocyclooctanone ( 9 ), methyl 5-nitro-2-oxocyclooctane-carboxylate ( 4 ), 2-acetyl-4-nitrocyclononanone ( 11 ), 2-acetyl-4-nitrocyclodecanone ( 15 ), benzyl 5-nitro-2,11-dioxocycloundecanecarboxylate ( 24 ), methyl 5-nitro-2,12-dioxocyclododecanecarboxylate ( 21 ), and 8-nitro-11-oxo-13-tridecanolide ( 7 ), which are intermediates, side products, or end products of the ‘Zip’ ring-enlargement reaction. The conformations of most of the medium-ring compounds are very similar to equal-sized ring compounds previously determine by other authors.     

Carbohydrate-based synthesis of crocacin: stereoselective Heck reaction of carbohydrate 5,6-ene- and 5,6-yne-derivatives with aromatic halides

The Heck reaction between a carbohydrate 5,6-ene derivative 9 and an aromatic halide exclusively gave rise to the β-carbohydrate-substituted trans-styrene derivative 8; while the corresponding Wittig reaction produced a cis/trans mixture in which the cis-isomer predominated. The application of the Heck reaction is described to synthesize the intermediate 5, commonly used in the synthesis of members of the crocacin family.     

Transformations of 2-(3-Hydroxy-3-methyl-1-butynyl)adamantan-2-ol >Catalyzed by Acids

Reaction of 2-(3-hydroxy-3-methyl-1-butynyl)adamantan-2-ol with acetonitrile under Ritter reaction conditions is accompanied by isomerization and partial hydration where the water addition to the triple bond occurs nonselectively. As a result of reaction carried out in the presence of 8 equiv of sulfuric acid a mixture was obtained of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]-acetamide, and N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-1-oxo-3-butyl]acetamide in ~10:3:2 ratio. In the presence of 2 equiv of the acid the mixture obtained consisted of N ²-[4-(1-acetylamino-2-adamantyl)-2-methyl-3-butyn-2-yl]acetamide, N ³-[1-(1-acetylamino-2-adamantyl)-3-methyl-2-oxo-3-butyl]acetamide, and 1-(1-acetylamino-2-adamantyl)-3-methyl-2-buten-1-one in the same ratio. In Rupe reaction conditions we obtained instead of the expected ,-unsaturated ketones a mixture of 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-1-one and 1-(1-hydroxy-2-adamantyl)-3-hydroxy-3-methylbutan-2-one in a 5:3 ratio.     

Zur Photochemie des Benzfurazans

Irradiation of benzofurazan ( 1 ) in benzene solution yields the azepine derivative 3 as the main photoproduct. Addition of methanol in the dark to the irradiated benzene solution of 1 results in the isolation of 3 together with a new product, methyl-1-cis, 3-cis-N-(4-cyano-buta-1, 3-dien-1-yl)-carbamate (1-cis, 3-cis- 2 ). Irradiation of 1 in methanol solution gives a mixture of the stereoisomeric methyl N-(4-cyano-buta-1, 3-dien-1-yl)-carbamates, from which the 1-trans, 3-cis isomer of 2 could be isolated in pure form. The observed photoproducts are formed via the reactive intermediates a , a nitrile-(nitrile oxide), and c , a nitrene, neither of which was isolated.     

Conformations of Z- and E-isomers of some chiral (1R,4R)-2-arylidene-p-menthan-3-ones

The ¹Í NMR method in combination with molecular simulation was used to study conformations of Z- and E-isomers of (1R,4R)-cis-2-(4-methoxyphenyl)benzylidene-p-menthan-3-one. In solutions the Z-isomer, unlike the conformationally uniform Å-isomer, is an equilibrium mixture of chair conformers with the substantial predomination of one form with the axially oriented methyl and equatorial isopropyl groups (75—78%). The enone group is more nonplanar in the Z-isomer than in the Å-isomer. For the isopropyl fragment, the equiprobable existence of trans- and two gauche-rotamers for the Z-isomer and a substantial predomination of gauche-forms in the case of the E-isomer were established.     

Valenzisomerisierung von cis-dienonen IV. Die vier stereoisomeren Formen von 4-Methyl-6-phenyl-3, 5-hexadien-2-on

(Z,Z)-4-Methyl-6-phenyl-3,5-hexadien-2-one ( 5 ) is converted to its (Z,E)-isomer 6 at 35° in the dark. This ready, uncatalysed cis,trans-isomerization is shown to proceed through 2H-pyran 9 . Irradiation of either stereoisomeric dienone 6, 7 or 8 at 0° produces a photostationary mixture of 5, 6, 7 and 8 in which the (Z,Z)-isomer 5 predominates.     

Umwandlung der diastereomeren 12- und 6-gliedrigen 1-Acetyl-2-methyl-1-cycloalkanole in 1-Äthinyl-2-methyl-1-cycloalkene

Conversion of the Diastereoisomeric 12-and 6-membered 1-Acetyl-2-methyl-1-cycloalkanols to 1-Ethynyl-2-methyl-1-cycloalkenes This paper is concerned primarily with a derivation of the E-configuration of 1-ethynyl-2-methyl-1-cyclododecene ( 10 ), which plays a role in mechanistic considerations on a method for ring expansion by 3 carbon atoms described in apreceding paper [1]. The derivation is based on an argument using the results of the dehydration of trans-1-acetyl-1-2-methyl-1-cyclododecanol ( 4 ) to 10 with phosphorus oxychloride and pyridine. That this dehydration is stereospecific can be concluded from its regiospecificity since the cis-hydroxyketone 3 dehydrates mainly to 1-ethynyl-12-methyl-1-cyclododecene (mixture of stereoisomers 11 and 12 ). An x-ray analysis shows the indicated configurations of the two hydroxyketones 3 and 4 . The direction (anti) of the stereospecificity of the double bond introduction during the 4 → 10 conversion is deduced from the similarity of the behaviour of the two stereoisomeric 1-acetyl-2-methyl-1-cyclohexanols 8 and 9 under the same conditions and from mechanistic considerations, which make it likeley that the anti-elimination behaviour observed in the 6-membered system has not changed over to a syn-elimination behaviour in the 12-membered system. The configurations of the two 6-membered hydroxyketones 8 and 9 correspond to those of the precursor1-ethynyl-2-methyl-1-cyclohexanols 6 and 7 , which were clarified with the help of ¹³C-NMR.-spectral coupling observations. It is of interest that the hydroxyketones 3, 4, 8 and 9 react with phosphorus oxychloride and pyridine so as to introduce both a double and a triple bond. It is probable that the double bond is introduced first, inasmuch as the triple bond is not introduced in the absence of activation of the hydroxyl group, as for instance in acetylcyclohexane. This can be used as an argument that the conversion of the acetyl to an ethynyl group in 3, 4, 8 and 9 does not affect the stereospecificity of the dehydration which introduces the ring double bond. 1-Acetyl-2-methyl-1-cyclododecene ( 24 ), a previously isolated compound with pleasant odor, was synthesized by hydration of 10 . This furnishes an argument for the E-configuration of 24 .     

Synthetic applications of electrochemically produced α-methoxyamides. Part 2. Oxidation of hydroxyproline derivatives

The electrochemical methoxylation of N-acetyl-4-hydroxyproline esters has been investigated. Both the free alcohol 3 and the corresponding 4-acetoxy derivative 4 as well as the cis-4-acetoxyproline 17 are methoxylated anodically preferentially at C(5), giving a mixture of stereoisomeric methoxy compounds. These mixtures can be used for further substitution as exemplified by the allylation of the methoxylated 4-acetoxy derivatives, giving substitution products preferentially trans to the acetoxy group although with low selectivity. The low selectivity is discussed in terms of kinetic vs. thermodynamic control.     

Conformational studies of dicyclohexylthallium chloride,bis(4-methylcyclohexyl)thallium chloride and bis(4-tert-butylcyclohexyl)thallium chloride by 1H NMR

Vicinal thallium–hydrogen coupling constants are used to discuss conformations in dicyclohexylthallium chloride, bis(4-methylcyclohexyl)thallium chloride and bis(4-tert-butylcyclohexyl)thallium chloride. Thallium does not have a very strong preference for equatorial positions in dicyclohexylthallium chloride, whereas bis(4-alkylcyclohexyl)thallium chlorides exist largely in one conformation. Bis(4-methylcyclohexyl)thallium chloride exists in three isomeric forms; the major product appears to be the cis-isomer (equatorial methyl, axial thallium), with the other two isomers probably containing thallium trans to the methyl group (axial thallium being preferred). The preference for the cis-isomer (equatorial tert-butyl, axial thallium) of bis(4-tert-butylcyclohexyl)thallium chloride is such that other isomers are not obtained.     

Mechanochemical-induced cis-to-trans isomerization of poly(2-ethynyl-3-n-octylthiophene) prepared with a Rh complex catalyst

Highly stereoregular polymerization of 2-ethynyl-3-n-octylthiophene was successfully performed with a [Rh(norbornadiene)Cl]₂ catalyst to produce the corresponding polymers in fairly high yields by using triethylamine or a mixture of it with other solvents as the polymerization solvent. We found that the obtained polymer using CHCl₃ was a mixture of cis-transoid form, ca. 68% and trans-transoid form, ca. 32% unlike our previous conjecture. Further, we found that the cis-to-trans isomerization can be also induced when the pristine predominant cis polymer was subjected to mechanochemical grinding (MCG) treatment at 77 K using a mortar filled with liquid nitrogen to decrease the cis content from ca. 68% to ca. 7%. The polymers obtained before and after the MCG treatment were characterized in detail using ¹H NMR, laser Raman, solution UV-vis, diffuse reflective UV-vis, and ESR methods in order to determine the geometry of the main-chain CC bonds in the polymer. The data showed that the polymer obtained by the treatment has a fairly distorted trans conjugation length, i.e., bent trans structure in which less mobile unpaired electrons generated by the rotational scission of the original cis CC bonds are stabilized.