从四氢叶叶酸辅酶模型合成麝香酮中间体2,1 5-十六二.酮

麝香酮是麝香中重要的具有生理活性的组分.自Ruzicka[1]确定其结构以来,化学家研究和发展了许多合成麝香酮的方法[2].Stoll[3]提出的由2,15-十六二酮经分子内环合后氢化得到麝香酮,其操作简便,但尚需解决2,15-十六二酮的来源问题.5,6,7,8-四氢叶酸辅酶在生物体内的功能和作用及仿生合成已成为仿生化学研究的重要课题[4].四氢叶酸辅酶在生物体内传递不同氧化态的-碳单元,当-碳单元处于甲酸氧化态时,活性部位是形成的咪唑啉环[5,6].因此,本文以咪唑啉盐作为四氢叶酸辅酶模型,与亲核试剂双格利雅试剂作用,仿生合成2,15-十六二酮.     

New synthetic method for cycloalkanedione

Ｔｈｅｓｙｎｔｈｅｔｉｃｍｅｔｈｏｄｓｉｎｌｉｔｅｒａｔｕｒｅｆｏｒｐｒｅｐａｒｉｎｇｃｙｃｌｏａｌｋａｎｅｄｉｏｎｅｃｏｍｐｏｕｎｄｓｕｓｅｄａｓｖａｌｕａｂｌｅｐｅｒｆｕｍｅｕｓｕａｌｌｙａｒｅｓｐｅｃｉａｌ,ｔｈｅｓｙｎｔｈｅｓｅｓｏｆｓｏｍｅｃｙｃｌｏａｌｋａｎｅｄｉｏｎｅｃｏｍｐｏｕｎｄｓａｒｅｅｘｔｒｅｍｅｌｙｄｉｆｆｉｃｕｌｔ.1,6ＣｙｃｌｏｄｏｄｅｃａｎｅｄｉｏｎｅｗａｓｐｒｅｐａｒｅｄｐｒｅｖｉｏｕｓｌｙｂｙＦｏｎｋｅｎｅｔａｌ.[1]ｖｉａｍｉｃｒｏｂｉｏｌｏｇｉｃａｌｈｙｄｒｏｘ…     

龙葵醛的新合成方法研究

龙葵醛是一种珍贵的香料 ,也是重要的化工原料 ,广泛应用于香料、医药、染料及农药等行业 .龙葵醛的工业生产以苯乙酮和一氯醋酸乙酯为原料 ,按 Darzens法合成[1,2 ] .苯乙酮与一氯醋酸乙酯在强碱作用下制得甲基苯基环氧丙酸酯 ,该酯经皂化、中和、水解成酸 ,再将该酸加热分解 ,得龙葵醛 .该方法操作比较复杂 ,产率和产品纯度也不高 .为了寻找产率高、纯度好且成本低的新制备方法已有广泛的研究 .Rivero等 [3]提出的 2 -甲基苯乙醇氧化法 ,尽管产率较高 ,但反应温度要在 -78℃ ,不利于工业化生产 .陈万之等[4 ] 利用各种铑螯合物作为催化剂…     

Novel Synthetic Method for Muscone

Muscone is a precious fragrant compound scarce in nature. Many attempts to synthesize this unique natural product have been carried out. In this work, a novel synthetic method for the preparation of muscone from 3‐methyl‐15‐hydroxypentadecanoate is provided. Benzimidazolium salt was used as tetrahydrofolate coenzyme model at formic acid oxidation level and Grignard reagent as nucleophile to which a one‐carbon unit was transferred. The biomimetic synthesis of muscone was successfully accomplished using the addition‐hydrolysis reaction of benzimidazolium salt with the Grignard reagent.     

The Kharasch type reaction of allylic halides with Grignard reagent in the presence of transition metal halides

The reaction of allylic halide with Grignard reagent in the presence of transition metal chloride has been investigated. Three reactions of allylic halide occurred competitively; (i) reduction to olefin, (ii) coupling with Grignard reagent to olefin (cross-coupling) and (iii) coupling with itself to 1,5-diene (homo-coupling). The relative importance of these reactions depends on both the structures of allylic halide and Grignard reagent, as well as on the transition metal salt utilized. The mechanism was discussed in terms of the allylic transition metal intermediate.     

Synthesis of Cycloundecanone from Benzimidazole Methiodide Salt

Cycloundecanone has been synthesized in several ways. Fawcett et al. prepared cycloundecanone by the reduction of Z-hydroxycycloundecanone'. Ruzicka et al. reported thesynthesis of cycloundecanone by the pyrolysis of the thorium salt of dodecanedioic acid=.Schank and Eistert synthesized cycloundecanone by ring contraction ofcyclododecanone'.Garbisch et al. improved the ring contraction reaction in over-all yields consistentlyranging between 85 and 90%'. Garbisch's method gave higher yields a…     

Alkylation des carbenoides par des nucleophiles. : II. Substitution nucleophile de l'halogene de carbenoides α phosphonates catalysee par le cuivre(I)

The addition of a catalytic amount (12%) of a copper(I) salt to a mixture of an α-lithio-α-chloroalkylphosphonate and an alkyllithium RLi or a Grignard reagent RMgX leads to the formation of a new organometallic reagent in which the R group has replaced the chlorine atom of the carbenoid. This nucleophilic alkylation of carbenoids can be performed with secondary-alkyl Grignard reagents, and with aryllithium, alkenyllithium and alkynyllithium reagents in good yields (60–80%).     

Tris(allyl) indium compounds: synthesis and structural characterization

Allyl and 2-methylallyl indium compounds were prepared by salt metathesis starting from indium trichloride and a Grignard reagent. They are highly fluxional in solution and reveal coordination numbers of the indium atoms of four and five in the solid state.     

Highly regioselective synthesis of gem-difluoroallenes through magnesium organocuprate SN2' substitution

[reaction: see text]. The reaction of gem-difluoropropargyl electrophiles with Grignard reagents is complicated by the inherent difficulty of executing nucleophilic substitutions on a CF2 group, and the facile formation of carbenoid intermediates arising from alpha-elimination of fluoride. In the presence of an excess amount of a copper salt, a Grignard reagent reacts with gem-difluoropropargyl bromide via an S(N)2' mechanism to produce gem-difluoroallene in high yield. If desired, the resulting difluoroallene can undergo a second nucleophilic attack on the CF2 terminus to yield a trisubstituted monofluoroallene through an addition-elimination mechanism.     

Studies on arylhydrazonoisoxazolinethiones. Behaviour of 4-arylhydrazono-3-phenyl-2-isoxazoline-5-thiones toward hydrazines,grignard reagents and alkylating agents

The 4-arylhydrazono-3-phenyl-2-isoxazoline-5-thiones 2 react with hydrazines to yield the 5-hydrazones 3 and 5 . The reaction of 2 with Grignard reagent resulted in addition of the reagent to the thiocarbonyl group to yield 7 . Treatment of 2 with diazomethane effected S - and N -methylation beside 1,2,3-triazole derivative 11 obtained through isomerisation. The potassium salt of 2 react with alkyl halides to yield the S-alkyl derivatives 12 .     

Reaction of polyepichlorohydrin with magnesium and grignard reagents

The reaction of polyepichlorohydrin with magnesium in tetrahydrofuran at reflux temperature was studied in the hope of obtaining a polymeric Grignard reagent. The polymeric Grignard reagent could not be obtained, but dechlorination occurred. It was confirmed that the Grignard reagent of polyepichlorohydrin was formed as an intermediate during the dechlorination. The reactions of polyepichlorohydrin with Grignard reagents were carried out in tetrahydrofuran at reflux temperature. Benzylmagnesium chloride and allylmagnesium chloride were used as Grignard reagents. It was found that the chlorine atom in polyepichlorohydrin can be replaced by benzyl and allyl groups. The extent of the substitution increased with increasing concentration of Grignard reagent. Dechlorination and scission of the ether linkage occurred simultaneously as side reactions.     

Nickel‐Catalyzed Facile [2+2+2] Cyclotrimerization of Unactivated Internal Alkynes to Polysubstituted Benzenes

A catalytic [2+2+2] cyclotrimerization of unactivated internal alkynes providing cyclotrimerization products in excellent yields with high regioselectivity is described. The transformation is accomplished by using a simple catalytic mixture comprising Ni(acac)₂, an imidazolium salt and a Grignard reagent at room temperature or 60 °C for 20 min or 1 h.     

bronsted酸性离子液体催化合成阿司匹林

以邻苯二胺和环丙基甲酸为原料,以多聚磷酸(PPA)为催化剂,在微波辐射下合成了环丙基苯并咪唑,用碘甲烷季胺化得到未见文献报道的环丙基苯并咪唑盐,通过苯并咪唑盐与Grignard试剂加成后水解反应制备环丙基甲基酮。经元素分析和红外光谱、质谱、核磁共振测试技术表征确证了结构。环丙基甲基酮为无色液体,合成环丙基甲基酮方法的产率为67%,为环丙基甲基酮提供了一种未见文献报道的合成方法。     

Ring-chain tautomerism as a factor in the reaction between Grignard reagents and substituted phthalides

With phthalide two equivalents of Grignard reagent react rapidly in a reaction which could not be controlled to give stepwise addition. In contrast, 3,3- and 4,7-disubstituted phthalides react with only one equivalent of organometallic reagent. The primary addition product formed from one equivalent each of phthalide and Grignard reagent exists in a ring-chain tautomerism whose position is controlled by the interaction between the substituents present in the phthalide and the alkyl group introduced by the Grignard reagent. With substituted phthalides, ring opening of the primary addition product is prevented by these interactions and thus a second equivalent of Grignard reagent does not react. In the absence of substituents, ring opening and the reaction of a second equivalent occurs.Somewhat related effects appear to exist in the reaction between Grignard reagents and phthalic anhydride and in the dehydration of substituted phthalyl alcohols to their corresponding phthalans.     

A novel method for the formylation of Grignard reagent

A facile and efficient method for the formylation of Grignard reagent was reported, and a new approach for the preparation of aldehydes from Grignard reagent and benzimida-zolium salts was provided.     

Regioselective arylation of 3-bromopyridine

The addition of aryl Grignard reagents to the 1-phenoxycarbonyl salt of 3-bromopyridine affords 2-aryl-5-bromo-1-phenoxycarbonyl-1,2-dihydropyridines and 4-aryl-3-bromo-1-phenoxycarbonyl-1,4-dihydropyridines. The crude dihydropyridines were aromatized with o-chloranil in refluxing toluene to give 4- and 6-aryl-3-bromopyridines. The regioselectivity of this two-step process, 6- vs. 4-substitution, was examined and found to be dependent upon the structure of the Grignard reagent. Unhindered aryl Grignard reagents, e.g., phenyl and 2-naphthyl, gave mainly 6-aryl-3-bromopyridines (49-52%) along with 9% of the 4-substituted isomer and less than 4% of the 2-aryl-3-bromopyridine. Hindered aryl Grignard reagents, e.g., o-tolyl and 1-naphthyl, are less regioselective. When a catalytic amount of cuprous iodide is present during the Grignard reaction, nearly exclusive 1,4-addition results. The crude 4-aryl-3-bromo-1,4-dihydropyridines were aromatized with p-chloranil to provide 4-aryl-3-bromopyridines in good yield and high isomeric purity. The sequential use of the cuprous iodide-catalyzed Grignard reaction and the “normal” Grignard reaction provided a regiospeci-fic synthesis of 3-bromo-6-(p-methoxyphenyl)-4-phenylpyridine from 3-bromopyridine.     

The quest for chiral Grignard reagents

The involvement of single electron transfer, i.e. of free radicals in the reactions of organomagnesium reagents could be detected with the aid of a chiral secondary Grignard reagent, in which the magnesium-bearing carbon atom is the sole stereogenic centre. So far, however, such reagents have not been accessible, because the standard preparation of Grignard reagents proceeds via free radicals. We review and summarize here our efforts to generate such a Grignard reagent 36 by asymmetric synthesis starting from an enantiomerically pure alpha-chloroalkyl-sulfoxide 30b using a sulfoxide/magnesium exchange reaction to give 33 followed by a carbenoid homologation reaction. Grignard reagent 36 turned out to be an ideal probe to learn about the extent to which SET is involved in reactions of organomagnesium reagents.     

Asymmetric synthesis of all the known phlegmarine alkaloids

The asymmetric synthesis of all four of the known natural phlegmarines and one synthetic derivative has been accomplished in 19-22 steps from 4-methoxy-3-(triisopropylsilyl)pyridine. Chiral N-acylpyridinium salt chemistry was used twice to set the stereocenters at the C-9 and C-2' positions of the phlegmarine skeleton. Key reactions include the use of a mixed Grignard reagent for the second N-acylpyridinium salt addition, zinc/acetic acid reduction of a complex dihydropyridone, and a von Braun cyanogen bromide N-demethylation of a late intermediate. These syntheses confirmed the absolute stereochemistry of all of the known phlegmarines.     

Evidence for the intermediacy of π-allylic metal complexes in the reaction of allylic halides with grignard reagent in the presence of transition metal halides

The reactions of allyl bromide and crotyl chloride with Grignard reagent catalyzed by π-allyl and crotyl metal complexes of nickel, cobalt, and iron, and the stoichiometric reaction of the complexes with the Grignard reagent have been examined. The similarity in catalytic behaviour of the complex and the corresponding metallic halide affords further evidence in support of the previous proposal that the π-allylic metal intermediate plays an important role in the catalytic reaction. The stoichiometric reaction suggests that the dependence of distribution of product in the catalytic process on the type of both allylic halide and metal is attributable to the facility of ligand exchange between the π-allylic complex and Grignard reagent.     

Sequential One‐Pot Addition of Excess Aryl‐Grignard Reagents and Electrophiles to O‐Alkyl Thioformates

The sequential addition of aromatic Grignard reagents to O‐alkyl thioformates proceeded to completion within 30 s to give aryl benzylic sulfanes in good yields. This reaction may begin with the nucleophilic attack of the Grignard reagent onto the carbon atom of the O‐alkyl thioformates, followed by the elimination of ROMgBr to generate aromatic thioaldehydes, which then react with a second molecule of the Grignard reagent at the sulfur atom to form arylsulfanyl benzylic Grignard reagents. To confirm the generation of aromatic thioaldehydes, the reaction between O‐alkyl thioformates and phenyl Grignard reagent was carried out in the presence of cyclopentadiene. As a result, hetero‐Diels–Alder adducts of the thioaldehyde and the diene were formed. The treatment of a mixture of the thioformate and phenyl Grignard reagent with iodine gave 1,2‐bis(phenylsulfanyl)‐1,2‐diphenyl ethane as a product, which indicated the formation of arylsulfanyl benzylic Grignard reagents in the reaction mixture. When electrophiles were added to the Grignard reagents that were generated in situ, four‐component coupling products, that is, O‐alkyl thioformates, two molecules of Grignard reagents, and electrophiles, were obtained in moderate‐to‐good yields. The use of silyl chloride or allylic bromides gave the adducts within 5 min, whereas the reaction with benzylic halides required more than 30 min. The addition to carbonyl compounds was complete within 1 min and the use of lithium bromide as an additive enhanced the yields of the four‐component coupling products. Finally, oxiranes and imines also participated in the coupling reaction.