Xanthone in synthesis: a reactivity profile via directed lithiation of its dimethyl ketal

Xanthone, as its dimethyl ketal, undergoes functionalization with a synthetically useful degree of regioselectivity using a lithiation protocol. The core structure is regenerated during the work-up. Monosubstitution at C-4 or C-1 and disubstitution at C-4 and C-5 or C-1 and C-5 are observed. The substitution pattern appears to be dependent upon the experimental conditions.     

( )-4-lithio-4-tosylbutenone dimethyl ketal: a new β-acylvinyl anion equivalent

( )-4-Lithio-4-tosylbutenone dimethyl ketal is regio and stereoselectively prepared by direct lithiation of the corresponding precursor with methyl-lithium at -20°C; the reaction of this β-acylvinyl anion equivalent with different electrophilic reagents (H₂O, D₂O, Me₃SiCl, Me₂S₂, Mel, CH₂=CHCH₂Br, BuⁱCHO, PhCHO, PhCOCl, Ac₂O) affords the corresponding functionalized compounds.     

Synthesis of 3-Aminopyrocatechol via Lithiated Intermediates

We report the synthesis of 3-aminopyrocatechol (7) through electrophilic amination of lithiated pyrocatechol, protected in the form of a ketal. For this purpose the lithiation reaction of protected pyrocatechol (1) was studied. The synthesis of compounds (3) was achieved by the reaction of organolithium derivative (2) and a series of electrophilic reagents. Lithium-t-butyl-N-tosyloxycarbamate (5) was used as the electrophilic aminating reagent. With the cupro derivative (4) the protecting groups in compound (6) are removed in an acid medium by heating in ethanol-HCl solution (4:1).     

Acetalation and Ketalation Catalyzed by SO42-/TiO2-MoO3

The catalytic activities of SO42-/TiO2-MoO3 in synthesizing cyclohexanone ethylene ketal,cyclohexanone 1,2-propanediol ketal, 2-propyl-1,3-dioxolane, 4-methyl-2-isopropyl-1,3-dioxolane,2-isopropyl-1,3-dioxolane, 4-methyl-2-isopropyl-1,3-dioxolane, butanone ethy-lene ketal and butanone 1,2-propanediol ketal were reported. It has been demonstrated that SO42-/TiO2-MoO3 is an excellent catalyst. Various factors concerned in this reaction have been investigated. The optimum conditions have been found, that is, the molar ratio of aldehyde/ketone to alcohol was 1:1.5 or 1:1.3,the mass ratio of the catalyst used to the reactants was 0.25～1.5%, and the reaction time was 45～60 min. Under this conditions, the yield of cyclohexanone ethylene ketal is 82.7%, cyclohexanone 1,2-propanediol ketal is 83.4%, the yield of 2-propyl-1,3-dioxolane is 68.1%,4-methyl-2-isopropyl-1,3-dioxolane is 87.5%, the yield of 2-isopropyl-1,3-dioxolane is 70.7%,4-methyl-2-isopropyl-1,3-dioxolane is 82.5%, the yield of butanone ethylene ketal is 74.1%, and butanone 1,2-propanediol ketal is 94.9%.Some equation and experiment results concerned of the synthetic acetals or ketals were listed as follows.     

Nouvolle synthcse de la dihydro-5,6 methoxy-6 2H-pyrannone-5

The α,β-ethylenic ketone 5 was obtained in 35% yield in four steps from 1. The intermediate product was a brominated ketal obtained in the form of a mixture of two isomers 6 and 7 . The stereochemistry and conformation was established by a study of the 250 MHz nmr spectra. During the dehydrobromination of 6 and 7 , a relatively easy isomerization of the α,β-ethylenic ketal occured by displacement of the double bond giving theβ,γ-ethylenic ketal 10 .     

Synthesis of 2-methyl-1,3-cyclopentanedione monoethylene ketal

Direct ketalization of 2-methyl-1,3-cyclopentanedione 3 led to the corresponding diethylene ketal 2. Carefully controlled hydrolysis of compound 2 afforded the monoethylene ketal 1 in high yield.     

Synthesis of the Thiazolone Analogue of the Acetylcholinesterase Inhibitor,Huperzine A

The preparation of an analogue 3a of the acetylcholinesterase inhibitor, huperzine A ( 1 ), is described in which the pyridinone moiety of the natural product is replaced with a thiazolone moiety. The synthesis started from cyclohexane-1,4-dione monoethylene ketal ( 7 ) by first annulating the thiazole ring using the Gewald protocol (→ 8 ; Scheme 1) and then constructing the bicyclo[3.3.1]nonane substructure using our previously described Michael addition/aldol condensation methodology (Scheme 3). The central problem was the protection of the thiazolone carbonyl group; only the 2-unsubstituted thiazole survived the reaction conditions of the first half of the synthesis. Refunctionalization was later effected by lithiation and subsequent chlorination with hexachloroethane ( 30→31 ). Compound 3a was ineffective in the acetylcholinesterase inhibition assay in concentrations up to 14 μM .     

An Indirect Method for Effecting the Addition of Methylmalonate to 2-Methylcyclohex-2-enone

The adduct (1a) of methylmalonate and 2-methylcyclohex-2-enone (2a) is best made by adding malonate to 2a to give 1b, protecting the ketone 0 in 1b as a ketal (3b), methylation to 3a and finally removal of the ketal.     

[2]Catenane Synthesis via Covalent Templating

After earlier unsuccessful attempts, this work reports the application of covalent templating for the synthesis of mechanically interlocked molecules (MiMs) bearing no supramolecular recognition sites. Two linear strands were covalently connected in a perpendicular fashion by a central ketal linkage. After subsequent attachment of the first strand to a template via temporary benzylic linkages, the second was linked to the template in a backfolding macrocyclization. The resulting pseudo[1]rotaxane structure was successfully converted to a [2]catenane via a second macrocyclization and cleavage of the ketal and temporary linkages.     

Practical synthesis of functionalized terminal alkynes, 3,3,3-triethoxypropyne and ketal protected prop-2-ynones

Practical and economical synthesis of synthetically valuable 3,3,3-triethoxypropyne, ketal protected phenyl and methyl substituents prop-2-ynones is described. Bromination and subsequent 18-crown-6 catalyzed elimination of triethylorthoacrylate and ketal protected terminal alkenes with methyl and phenyl substituent which are inturn readily available from triethylorthopropionate, 3-chlorobutan-2-one and propiophenone afforded multigram quantities (>10?g) of corresponding functionalized terminal alkynes. Exploration of the synthetic utility of these alkynes is also demonstrated by the acetylenic substitution of the phenylalaninol derived 1,2-cyclic sulfamidate to deliver chiral alkynylated amines.     

钨硅酸的制备及其在催化合成缩酮(醛)中的应用

本文探讨了钨硅酸的制备方法,以合成环己酮1,2-内二醇缩酮为例验证钨硅酸的催化活性,并探讨了合成其它缩酮（醛）的适宜条件,得到的收率分别为：环己酮1,2-丙二醇缩酮85．5％、环己酮乙二醇缩酮89．6％、丁酮乙二醇缩酮79．5％、丁醛乙二醇缩醛89．1％、丁醛1,2丙二醇缩醛81．5％。     

Neue acetonylsubstituierte Azole II. 3-Acetonyl-1,2,4-oxadiazole, 2-Acetonyl-1,3,4-oxadiazole und 5-Acetonyl-1,2,4-thiadiazole

3-Acetonyl-1,2,4-oxadiazoles and 2-acetonyl-1,3,4-oxadiazoles are accessible starting with the ketal of acetoacetamide oxime and the ketal of acetoacetic acid hydrazide, respectively. 5-Acetonyl-1,2,4-thiadiazoles are obtained from 5-chloro-1,2,4-thiadiazoles andtert.-butyl acetoacetate. These Acetonyl-azoles are starting materials for three series of azolylvinyl phosphates and phosphonates.

Herrn Prof. Dr.Klaus Weissermel zu seinem 60. Geburtstag.     

Allylsilane and diallylsilane reactions with functionalized ethylene ketals or benzodioxoles

The bis-allylation of ethylene ketal and catechol ketal derivatives of 2,5-hexanedione occurred with a great stereoselectivity. The tetraallylation of bis-catechol ketal derivatives of 2,5-hexanedione and 2-methyl-1,3-cyclohexanedione or the diallylation of 4-phenylbutan-2-one derivatives arise in good yields and these compounds were suitable substrates for ring-closing metathesis leading to 4,4-dialkylcyclopentenes. Condensation of 1,8-bistrimethylsilyl-2,6-octadiene (Bistro) with 4-phenylbutan-2-one catechol ketal derivatives or 2-methylcyclohexan-1,3-dione mono catechol ketal afforded in good yields cyclic and tricyclic products 12 or 23, respectively.     

A highly stereoselective approach to the synthesis of functionalized pyran derivatives by Lewis acid assisted ketal reduction and allylation

Reduction of bicyclic ketal 1 gave functionalized pyran derivatives 7a or 7b in a highly stereoselective manner, depending upon the reduction conditions utilized. For example, treatment of ketal 1 with TiCl4/Et3SiH produced exclusively diol 7b with the 2,5-syn relationship in good yield. Alternatively, reduction of ketal 1 by DIBALH gave 2,5-anti-diol 7a stereoselectively. Alane reductions of ketal 1 were highly stereoselective also; however, the syn/anti selectivity observed was strongly dependent on the ratio of reagents employed for in situ generation of the alane. Lewis acid catalyzed allylation of ketal 1 gave pyran 10 in a stereospecific alkylation reaction.     

高岭土负载SO42-/ZrO2-TiO2催化剂的制备及其在缩酮合成中的应用

以经H2SO4处理焙烧的高岭土为载体,制备了以其负载的SO2-4/ZrO2-TiO2固体酸催化剂。 用FT-IR、XRD和NH3-TPD等测试技术表征了催化剂的微观结构及酸强度,考察了对环己酮乙二醇缩酮反应的催化活性及稳定性。 结果表明,酸化处理使高岭土表面酸量增加,但酸强度变化不大,而其负载SO2-4/ZrO2-TiO2后,经500 ℃焙烧3 h其酸量及酸强度显著升高。 环己酮用量为0.2 mol、乙二醇0.24 mol、催化剂1.2 g、带水剂环己烷15 mL,回流反应70 min后,缩酮收率可达96.8%,催化剂重复使用5次收率保持在90%以上。     

Regioselective dienolate formation and alkylation of alkyl 2-methyl cyclohexene-1 carboxylates

Exocyclic deprotonation and α alkylation with methyliodide of title compounds have been observed. A clarification of Hagemann ester ethylene ketal reactivity toward strong bases is given.     

Diazines. IX. Metalation of 2-chloro, 2-methoxy and 2-pivaloylaminoquinoxaline

The lithiation of 2-chloro, 2-methoxy and 2-pivaloylaminoquinoxaline was studied. In the case of 2-chloro and 2-methoxyquinoxaline the simultaneous formation of dimers could not be avoided. The resulting lithio derivatives were reacted with carbonyl compounds and iodine. Yields in excess of 50% were obtained.     

Stereo- and regioselective oxymercuration - demercuration of bicyclo[3.2.1]Oct-2-ene skeleton

The oxymercuration - demercuration of ethylene ketal of bicyclo-[3.2.1]oct-2-en-8-one is reported. This reaction proceeds with high regio- and stereoselectivity.     

An unexpected acid mediated rearrangement of monoethylene ketal of 2-methyl-2-(3-methylbut-2-en-1-yl)cyclohex-4-ene-1,3-diones to chromane

We herein report a serendipitously observed acid mediated rearrangement of monoethylene ketal of 2-methyl-2-(3-methylbut-2-en-1-yl)cyclohex-4-ene-1,3-diones to Dihydrobenzopyran and demonstrated the application of this methodology in the construction of core carbon scaffolds of dimethoxyajacareubin, cariphenone-A and crotamadine.     

Ortho lithiation of 2-, 3-, and 4-methoxypyridines

The ortho lithiation of 2-,3-, and 4-methoxypyridine was effected using mesityllithium as the metalating base.