Synthesis of arotinoid acid and temarotene using mixed (Z)-1,2-bis(organylchalcogene)-1-alkene as precursor

An efficient and novel total synthesis of the two bioactive retinoids temarotene and arotinoid acid (TTNPB) is described. The key steps in this process include the regio and stereoselective hydrotelluration of thioacetylene 9 and Te/Li transmetalation of mixed (Z)-1,2-bis(organylchalcogene)-1-alkene (Z)-3. The subsequent reaction involving the β-phenylthio vinyl lithiated intermediate 10 with dimethyl sulfate gave the (E)-vinyl sulfide 11. The Ni⁺² cross-coupling of 11 with the corresponding phenylzinc bromide and p-oxazoline phenylzinc bromide 12 afforded the respective temarotene 2 and retinoid-oxazoline substituted 13. Finally, compound 13 was deprotected with HCl to furnish arotinoid acid (TTNPB) 1.     

Stereoselective Synthesis and Diels-Alder Reactions of (Z)- and (E)-1,2-bis(Phenylthio)-1,3-Butadiene

Bromination of 3-phenylthio-2-sulfolene (2) with N-bromosuccinimide gave 2-bromo-3-phenylthio-2-sulfolene (3) which was converted mainly to 2,3-bis(phenylthio)-2-sulfolene (4) by treatment with sodium phenylthiolate. Thermal desulfonylation of 4 at different temperatures in the presence of a base (DBU) yielded stereoselectively the (Z)- and (E)-1,2-bis(phenylthio)-1,3-butadiene (6). These two geometric isomers could be thermally interconverted. The Diels-Alder reactions of 6 were also investigated. Only the (Z)-diene 6a could undergo the Diels-Alder reaction; the (E)-diene 6b was in situ converted to the Z isomer before undergoing (he Diels-Alder reaction. The reaction of 6a with N-phenylmaleimide gave the cycloaddition product 7 with complete endo selectivity, but under daylight or during chromatography it readily underwent a thioallylic rearrangement to yield 8 with inversion of configuration. The cycloaddition of 6a with methyl acrylate proceeded regiospecifically, but generating a mixture of endo and exo isomers. The endo/exo ratio could be increased by using ZnCl₂ as the catalyst.     

The stereoselective synthesis of (Z)-HFCCFZnI and stereospecific preparation of (E)-1,2-difluorostyrenes from (Z)-HFCCFZnI via an unusual Pd(PPh3)4-Cu(I)Br co-catalysis approach or (Z)-HFCCFSnBu3

(Z)-HFCCFZnI was stereoselectively synthesized from activated zinc dust and (Z)-HFCCFI that was synthesized from chlorotrifluoroethene in a sequential manner. Compared to (E)-HFCCFZnI, (Z)-HFCCFZnI was more challenging to prepare in terms of sluggish metallation and formation of by-products, and underwent slower and incomplete Negishi coupling with aryl iodides. In a modification of Negishi coupling, (E)-α,β-difluorostyrenes were stereospecifically prepared in good to excellent yields under mild conditions from aryl iodides and (Z)-HFCCFZnI with the co-catalysis of Pd(PPh₃)₄/Cu(I)Br. Experimental investigation and mechanistic rationalization suggested that Cu(I)Br would be a scavenger of free ligands for the facilitation of Pd(PPh₃)₂ formation, and a supplier of ligand for the metathesis process. Alternatively, (Z)-HFCCFSnBu₃ and aryl iodides with an electron-withdrawing group underwent Stille-Liebiskind coupling to afford (E)-α,β-difluorostyrenes.     

Synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-pyridyl) (or n-quinolyl)-1,3-butadienes from n-(2′-chloroethenyl)pyridine (or quinoline)

The homocoupling reaction between the conjugated n-(2-chloroethenyl)pyridine; n, 2-, 3- and 4- (or quinoline; n, 2- and 4-) mediated by zero-valent nickel complexes at room temperature affords to the corresponding 1,4-diaryl-1,3-butadiene, always as the 1E,3E stereoisomer. The yield in 1,4-diaryl-1,3-butadiene increases with the nickel catalyst and hence, the active zero-valent nickel catalyst is not regenerated during the homocoupling reaction.The stereospecific synthesis of (1Z,3Z)-1,4-di(4′-pyridyl)-1,3-butadiene stereoisomer was efficiently carried out by partial hydrogenation of the appropriate 1,4-di(4′-pyridyl)-1,3-butadiyne.     

Stereospecific synthesis of conjugated (1E,3E)- and (1Z,3Z)-1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes from 2-chloro-1-(n-N,N-dimethylaminophenyl)ethenes: fluorescence properties

The conjugated 1,4-di(n-N,N-dimethylaminophenyl)-1,3-butadienes (n=o-, m-, p-) were efficiently synthesised by homocoupling of the appropriate 2-chloro-1-(n-N,N-dimethylaminophenyl)ethene (n=o-, m-, p-) with stoichiometric amounts of zerovalent nickel complexes. The 1,3-butadienes were obtained as a mixture of stereoisomers, with independence of the starting E or Z chlorovinyl isomer. Moreover, the stereospecific (Z,Z) stereoisomer was obtained by partial hydrogenation of the corresponding 1,3-butadiyne, while the stereospecific (E,E) stereoisomer was obtained by exposure to the sunlight radiation of the (Z,Z) or the (Z,E) compound in ethanol.     

Stereospecific preparation of symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes from 1-bromo-1-fluoroalkenes

A straightforward method to prepare symmetrical (1Z, 3Z)- and (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes is described. High E/Z ratio 1-bromo-1-fluoroalkenes, prepared by isomerization from the E/Z ≈ 1:1 isomeric mixtures, reacted with Bu₃SnSnBu₃ and Pd(PPh₃)₄ to afford (1Z, 3Z)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes in good yield. (Z)-1-Bromo-1-fluoroalkenes, which were prepared by kinetic reduction from 1-bromo-1-fluoroalkenes (E/Z ≈ 1:1), can undergo similar reaction with Bu₃SnSnBu₃ and Pd(PPh₃)₄/CuI to prepare (1E, 3E)-2,3-difluoro-1,4-disubstituted-buta-1,3-dienes.     

Thermal and photochemical isomerization of exocyclic 1,3-dienes: 1,1-diphenyl-3,4-bis(trimethylsilylmethylene)-1-silacyclopentane s-cis(E,E)

This paper describes the photochemical and the thermal isomerization of s-cis(E,E) 1,1-diphenly-3,4-bis(trimethylsilylmethylene)-1-silacyclopentane (1a). Under thermal conditions a 1,3-sigmatropic of the methylene hydrogen occurs, yielding the s-trans isomer (1b). The photochemical irradiation of (1a) at 300 nm for 1 h in deoxygenated benzene gives the corresponding s-cis(E,Z) isomer (1c) and then the s-cis(Z,Z) isomer (1d) after prolonged irradiation (3 h). There was no evidence for the formation of the corresponding cyclobutene resulting from the ring closure of the exocylic diene.     

Facile Synthesis of (Z,E)-9,11-Hexadecadienal,the Major Sex Pheromone Component of the Sugarcane Borer Diatraea saccharalis: An Efficient Strategy for Synthesis of (Z,E)-Dienic Pheromones

Practical and improved procedures for the synthesis of 7-bromo-(Z,E)-4,6-heptadienal by Pd(II)-catalyzed coupling reaction were developed. Based on the improved method, an efficient and stereoselective synthesis of (Z,E)-9,11-hexadecadienal, the main pheromone component of the sugarcane borer, Diatraea saccharalis, was achieved in 38% overall yield, which more desirable then previously reported methods. The stereochemistry relied on cross-coupling between Grignard reagent and protected 7-bromo-(Z,E)-4,6-heptadienal. The concise and facile synthetic strategy described herein provided a generally synthetic approach to other (Z,E)-dienic compounds.     

Novel (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles from (E)- and (Z)-3-styrylchromones: the unexpected case of (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles

An efficient synthetic method for the preparation of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles has been developed. The reaction of (E)- and (Z)-3-styrylchromones with hydrazine hydrate afforded the corresponding (E)- and (Z)-4-styrylpyrazoles, respectively, saved 4′-nitro-derivatives where both (E)- and (Z)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations was discussed and the stereochemistry of all products was assigned by NMR experiments.     

Stereoselective synthesis of (Z)-β-fluoro-α,β-unsaturated esters from (Z)-2-fluoro-1-alkenyliodonium salts

(Z)-β-Fluoro-α,β-unsaturated esters were stereoselectively synthesized from (Z)-2-fluoro-1-alkenyliodonium salts by the Pd-catalyzed methoxycarbonylation reaction. The reaction proceeded at room temperature and various functional groups on the substrate can tolerate the reaction conditions.     

Total synthesis of 1-(Z)-atractylodinol

The total synthesis of 1-(Z)-atractylodinol, a natural polyacetylenic alcohol with several biological activities, has been achieved using a newly developed telluride synthon and a novel use for the Negishi type coupling reaction employing vinyl tellurides.     

Efficient preparation of (Z)-alkenyl derivatives from (Z)-vinyl (N,N-diisopropyl)carbamate via Ni-catalysed coupling reactions

A (Z)-vinyl (N,N-diisopropyl)carbamate treated with Grignard reagents, under Wenkert Nickel-catalysed conditions, gave access to several substituted (Z)-alkenyl derivatives. These Nickel-catalysed reactions, carried out with vinyl-, phenyl-, p-methoxyphenyl-, trimethylsilylmethylmagnesium bromide and benzylmagnesium chloride, led to the corresponding (Z)-alkenyl derivatives in good yields and high stereoselectivities.     

Synthesis and Crystal Structure of (Z)-Ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-4-carboxylate

The compound (Z)-ethyl 5-(phenylamino)-3-(phenylimino)-3H-1,2-dithiole-4-carboxylate 3 has been synthesized by the reaction of ethylacetoacetate 1 and phenylisothiocyanate 2. Its structure has been established by ¹H NMR, ¹³C NMR, infrared, mass spectra, and x-ray crystallography.      

Novel and efficient approach to (Z)-4-trifluoroethylidene-1,3-dioxolane derivatives via (trifluoromethyl)ethynylation of ketones and aldehydes

Perfluoroalkylated 4-trifluoroethylidene-1,3-dioxolanes 2a-p were prepared in quantitative yields from the reaction of new stable (trifluoromethyl)ethynylation reagent 1a with TBAF at −15 °C for 10 min, followed by treatment with phenyl perfluoroalkylated ketones at room temperature. The use of aldehydes under the same reaction condition afforded 1,3-dioxolanes 2q-r in good yields. The reaction of 1a with TBAF, followed by treatment with aldehydes or ketones at −15 °C for 10 min and then with trifluoroacetophenone at room temperature provided 1,3-dioxolane derivatives 2s-t in good yields. Tetrabutylammonium trifluoropropynylide [II] was treated with benzaldehyde derivatives at −15 °C for 10 min, followed by treatment with trifluoroacetophenone, to give the corresponding 1,3-dioxolanes 2u-z and 1,3-dioxines 3u-z with different reaction condition.     

Synthesis of substituted 1,2-di(alkylsulfonyl)indolizines. Molecular and crystal structure of 3-(4-fluorobenzoyl)-6-methyl-1,2-di(propylsulfonyl)indolizine

The reactions of substituted pyridinium salts with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes proceed regiospecifically. Heating of these reagents in chloroform in the presence of a threefold excess of Et₃N affords substituted 1,2-di(alkylsulfonyl)indolizines in high yields. The structures of the reaction products were confirmed by physicochemical methods, including X-ray diffraction. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1205–1209, May, 2005.     

A practical, stereospecific route to 18-, 19-, and 20-hydroxyeicosa-5(Z),8(Z),11(Z),14(Z)-tetraenoic acids (18-, 19-, and 20-HETEs)

Suzuki-Miyaura cross-coupling of cis-vinylbromide 6, obtained in three steps from diol 4, with functionalized boranes provides a practical, stereospecific route to the title CYP P450 eicosanoids.     

氯化铯催化芳硒化钠对炔硒醚加成合成(Z)-1,2-二芳硒基烯

氯化铯催化下, 以商业DMF作溶剂, 芳硒化钠与炔硒醚在室温、氮气保护下反应, 立体选择地生成(Z)-1,2-二芳硒基烯.     

Synthesis of 9-arylamino- and (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)benzaldehydes with aryl amines

Heating mixtures of 2-(pyrrol-1-yl)benzaldehydes and aryl amines under argon afforded 9-arylamino-9H-pyrrolo[1,2-a]indoles, via cyclization of the resulting 2-(pyrrol-1-yl)benzaldimine intermediates. Heating in the presence of oxygen afforded (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles, which were successfully hydrolyzed with hydrochloric acid to give pyrrolo[1,2-a]indol-9-ones.     

气相色谱法测定化合物中R-氯甘油的含量

建立了气相色谱法测定化合物中R-氯甘油含量的方法.试验条件:FID检测器,检测器温度为290℃;进样口温度280℃,分流比1∶1;载体为氮气,流速5 m L/min;柱温初始温度75℃,保持3 min,以20℃/min的升温速率上升到150℃,再以8℃/min的升温速率上升到180℃,以30℃/min的升温速率上升到240℃,并维持12.5 min.试验结果:空白溶剂不干扰测定,R-氯甘油峰与其他残留溶剂峰分离度良好,检测限为2.06 ng,定量限为6.58 ng,方法专属、灵敏.在80～200μg/ml范围内,R-氯甘油浓度与峰面积的线性关系良好,线性方程为y=2.558 8x-62.469,线性回归系数r为0.999 4.同一溶液连续进样6次,结果之间的RSD低于1.0%,方法进样精密度良好.同一均质样品平行测定6份,结果之间的RSD低于1.5%,方法重复性良好.加样回收率结果均介于98%～102%之间,方法准确度良好.方法适用于胆碱类物质中R-氯甘油含量的测定.