Nitrile anion cyclization with epoxysilanes followed by Brook rearrangement/ring-opening of cyclopropane nitriles/alkylation

[reactions: see text] The reaction of delta-silyl-gamma,delta-epoxypentanenitrile derivatives 9-12 with a base and an alkylating agent affords (Z)-delta-siloxy-gamma,delta-unsaturated pentanenitrile derivatives via a tandem process that involves the formation of a cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring. Exclusive formation of a (Z)-derivative from trans-epoxides is explained by the reaction pathway that involves a backside displacement of the epoxide by the alpha-nitrile carbanion and the O-Si bond formation followed by concerted processes involving Brook rearrangement and the anti-mode of eliminative ring fission of the cyclopropane from the rotamer 19. The fact that (E)-isomers are exclusively obtained from cis-epoxides and alpha-cyclopropyl-alpha-silylcarbinol derivative 26 provides experimental support for the proposed pathway.     

A rhodium-catalyzed C-H activation/cycloisomerization tandem

A reaction cascade comprising a rhodium-catalyzed C-H activation, a subsequent hydrometalation of an alkylidene cyclopropane in vicinity, regioselective C-C bond activation of the flanking cyclopropane ring, followed by reductive elimination of the resulting metallacycle, opens a new entry into functionalized cycloheptene derivatives. This crossover of C-H activation and higher order cycloaddition has been performed in two different formats, either using alkylidenecyclopropanes with a lateral vinylpyridine moiety or with a pending aldehyde group as the trigger. The reaction tolerates various functional groups, leaves chiral centers alpha to the reacting sites unaffected, and proceeds with excellent stereoselectivity. Labeling experiments support the proposed mechanism explaining the observed net cycloisomerization process.     

Palladium-catalyzed oxidative activation of arylcyclopropanes

Palladium chloride-catalyzed intramolecular activation of electroneutral cyclopropane derivatives results in cleavage of the cyclopropane ring followed by formation of heterocyclic derivatives. Phenols, carboxylic acids, and amide groups were considered as substituents ortho to the cyclopropane ring in this catalytic activation chemistry. The regioselectivity observed in the case of amide-containing substrates was different from that of carboxylic acid-containing substrates, ruling out simple cyclopropane isomerization followed by a Wacker oxidation as the mechanistic pathway. [reaction: see text]     

Application of divergent multi-component reactions in the synthesis of a library of peptidomimetics based on γ-amino-α,β-cyclopropyl acids

The multi-component condensation of organozirconocene, aldimine and zinc carbenoid was applied to the stereoselective synthesis of cyclopropane amino acid derivatives. These compounds served as scaffolds for the preparation of a 46-member library. The C- and N-termini of the cyclopropane amino acid derivatives were diversified by condensations with ten amines and ten acylating agents, respectively. To improve yields and accelerate library synthesis, most products were prepared under microwave irradiation and purified by polymer-bound scavengers and SPE methodology. All compounds were analyzed by LC-MS and a representative selection was fully characterized.     

Bonding Properties of Cyclopropane and Their Chemical Consequences

Among the cyclic compounds of carbon, cyclopropane and its derivatives are outstanding by virtue of their unusual structural, spectroscopic, and chemical properties. The cyclopropane ring more closely resembles the C?C double bond than the cyclobutane ring: it is a small ring with “double bond character”. Cyclopropyl and vinyl groups interact with neighbouring π-electron systems and p-electron centers; both cyclopropane derivatives and olefins form metal complexes, and add strong acids, halogens, and ozone; they both undergo catalytic hydrogenation and cycloadditions. While distinct differences in reactivity do exist–the double bond usually being more reactive than the three-membered ring–there are no fundamental differences in behavior.–Although cyclopropane derivatives have been known for more than 90 years, intensive studies have been limited to the past 25 years. The development of carbene chemistry has rendered cyclopropane derivatives far more readily accessible. In recent years, the synthetic potential of the small-ring function has been increasingly exploited. A considerable number of newly developed methods utilizing this approach clearly demonstrates that the reactivity of the cyclopropene ring, like that of the C?C double bond, qualify it as a “functional carbon group”. This development is in full swing; we may therefore justifiably devote considerable effort to the study of cyclopropane chemistry.     

环丙烷衍生物在D2O离子体系中的H/D交换反应

在D2O化学反应气条件下研究了环丙烷衍生物的H/D交换反应特性.发现了三种新的产物离子[M+1]+、[M+2]+和[M+3]+.应用碰撞诱导碎裂(CID)技术研究了这些离子的碎裂反应特性.实验结果表明三种新的产物离子是由反应物与试剂离子之间发生H/D交换反应生成的.并获得了环丙烷衍生物结构中活泼氢位置及其数量的信息.     

Grignard Reagent/CuI/LiCl‐Mediated Stereoselective Cascade Addition/Cyclization of Diynes: A Novel Pathway for the Construction of 1‐Methyleneindene Derivatives

Diynes containing a cyclopropane group smoothly undergo a novel intramolecular and stereoselective cascade addition/cyclization reaction to produce the corresponding 1‐methyleneindene derivatives in moderate to good yields. This interesting transformation is mediated by Grignard reagent/CuI with LiCl as an additive under mild conditions. The obtained product can easily be further functionalized through cyclopropyl ring opening. A plausible reaction mechanism has also been presented on the basis of deuterium labeling and control experiments.     

Synthesis of thiadiazoles and 1,2,4-triazoles derived from cyclopropane dicarboxylic acid

New heterocyclic derivatives of cyclopropane dicarboxylic acid comprising thiadiazole and 1,2,4-triazole moieties are reported. Reaction of 1,1-cyclopropane dicarboxylic acid (1) with thiosemicarbazide and phosphorous oxychloride resulted in 1,1-bis (2-amino-1,3,4-thiadiazol-5- yl)cyclopropane (2). Cyclopropane dicarboxylic acid thiosemicarbazide (6) was converted into 1,1-bis(3-thio-4H-1,2,4-triazol-5-yl) cyclo- propane (7) by ring closure in an alkaline medium. The thiadiazole 2 and the triazole 7 were converted into a variety of derivatives.     

Comments on the electronic properties of cyclopropane,cyclobutane, and cyclohexane

Spectral quantities of cyclopropane, cyclobutane, cyclohexane, and of several derivatives, have been calculated by a semiempirical all-valence electron SCF-CI MO method. In cyclopropane, HOMO is practically localized in the carbon-frame, and LVMO is purely so. In cyclobutane, these two MO's are based on C-H bonds, while cyclohexane holds an intermediate position. Despite the overall similarity-experimental and computed-of the spectra of these molecules, assignments are non-parallel. Like cyclopropane, cyclobutane can extend conjugation, but to a diminished degree; cyclohexane behaves in this respect like an acyclic alkane. An interpretation of this gradation, in terms of the nature of high-lying MO's, is proposed.     

化学修饰在质谱中的应用 3: 环丙烷脂肪酸的苯并 唑衍生物的质谱特征

本文作者曾成功地利用苯并 唑衍生物直接鉴定出不饱和脂肪酸中酸双键位置。本文在该基础上继续研究了长链环丙烷酸的苯并 唑衍生物的质谱, 结果证明脂肪链上的环丙烷基部位在其质谱上可得到特征的反映, 根据谱中碳链系列离子峰的质量间隔, 就可确定出环丙烷基在脂肪链的位置。     

Silylium‐Ion‐Promoted (5+1) Cycloaddition of Aryl‐Substituted Vinylcyclopropanes and Hydrosilanes Involving Aryl Migration

A transition‐metal‐free (5+1) cycloaddition of aryl‐substituted vinylcyclopropanes (VCPs) and hydrosilanes to afford silacyclohexanes is reported. Catalytic amounts of the trityl cation initiate the reaction by hydride abstraction from the hydrosilane, and further progress of the reaction is maintained by self‐regeneration of the silylium ions. The new reaction involves a [1,2] migration of an aryl group, eventually furnishing 4‐ rather than 3‐aryl‐substituted silacyclohexane derivatives as major products. Various control experiments and quantum‐chemical calculations support a mechanistic picture where a silylium ion intramolecularly stabilized by a cyclopropane ring can either undergo a kinetically favored concerted [1,2] aryl migration/ring expansion or engage in a cyclopropane‐to‐cyclopropane rearrangement.     

环丙烷氨基酸合成研究进展

本文综述了合成环丙烷氨基酸类化合物的近期研究进展。制备方法包括对简单氨基酸衍生物的亲核环烷基化、类卡宾加成以及简单环丙烷化合物的衍生化合成等。在手性合成中利用了天然或合成的光学活性化合物。     

Synthesis of gem-dialkoxycarbonylcyclopropane derivatives from olefins by the reaction with dibromomalonic esters and copper in dimethyl sulphoxide

A novel method for the synthesis of gem-dialkoxycarbonylcyclopropane derivatives is reported which involves the reaction of olefins with dibromomalonic esters and Cu in dimethyl sulphoxide. The reaction was applicable to a wide range of olefins and proceeded smoothly at moderate temperature to give the cyclopropane derivatives often in good yields. Cu was converted to Cu(II) bromide during the reaction. The reaction was weakly electrophilic and proceeded non-stereospecifically, and a stepwise mechanism involving addition and elimination appeared favourable for the reaction. In contrast, in the previously reported examples of the cyclopropanation of olefins by organic gem-dihalides and Cu in an aromatic hydrocarbon, Cu was converted to Cu(I) halides and a concerted cycloaddition of carbenoid intermediates appeared favourable.     

Modular synthesis of a new family of tripodal ligands, all-cis-1,2,3-tris(diphenylphosphinomethyl)cyclopropane and relatives

Bisbenzyl-protected all-cis-1,2,3-tris(hydroxymethyl)cyclopropane has been obtained in three steps from commercially available cis-2-butene-1,4-diol (75% overall yield) and used to prepare a number of all-cis-1,2,3-trisubstituted cyclopropane derivatives. Among them, the new tripodal ligand all-cis-tris(diphenylphosphinomethyl)cyclopropane (TriCyp-PPP) has been demonstrated to furnish-with pi-allylpalladium chloride dimer-a highly active catalyst for the allylation of diethyl methylmalonate enolate with allyl acetate.     

Lewis acid-catalyzed rearrangement of multi-substituted arylvinylidenecyclopropanes

An interesting rearrangement of arylvinylidenecyclopropanes having three substituents at the 1- and 2-positions of the corresponding cyclopropane catalyzed by Lewis acids to give 6aH-benzo[c]fluorine derivatives via a double intramolecular Friedel-Crafts reaction or to give an indene derivative via an intramolecular Friedel-Crafts reaction is described.     

Rearrangements and cyclizations—XVI: Ring-opening reactions of 1,1-diacetylcyclopropane with hydrazine and hydroxylamine derivatives as the novel synthesis of β-X-ethyl substituted pyrazoles and isoxazoles

The reactions of 1,1-diacetylcyclopropane (1) with a number of hydrazine and hydroxylamine derivatives proceed via cyclopropane ring opening with incorporation of external nucleophile (solvent) to give the 4-β-X-ethyl derivatives of 3,5-dimethylpyrazoles and -isoxazoles, a novel route to these heterocycles. This ring cleavage occurs especially smoothly in water as a solvent. A rationale for this unusually mild nucleophilic cyclopropane ring opening is discussed.     

Some aminophosphinocarboxylic acids and their derivatives

The addition of Schiff bases of α-aminoacid esters to vinylphosphoryl compounds was studied as a method for the synthesis of phosphinothricin and its analogues. The reaction was found to proceed smoothly in DMSO in the presence of strong nitrogen bases and under the conditions of phase transfer catalysis. The Claisen condensation of β-phosphorylated propionitrile with diethyl oxalate was studied; phosphorylated derivatives of hydroxycitraconic acid nitrile were prepared on hydrolysis; transformation of such a derivative into a cyclic imide as well as into trimethylsilyl esters of these acids and their Z → E transformation were investigated. Cyclization reactions between α,ω-dibromoalkanes and phosphoryl compounds containing an active methylene group affording cyclopropane and other cyclic derivatives were studied. The cyclopropane ring is cleaved by amines to give aminophosphinocarboxylic acids.     

Rhodium‐Catalyzed [3+2+2] and [2+2+2] Cycloadditions of Two Alkynes with Cyclopropylideneacetamides

It has been established that a cationic rhodium(I)/H₈‐binap complex catalyzes the [3+2+2] cycloaddition of 1,6‐diynes with cyclopropylideneacetamides to produce cycloheptadiene derivatives through cleavage of cyclopropane rings. In contrast, a cationic rhodium(I)/(S)‐binap complex catalyzes the enantioselective [2+2+2] cycloaddition of terminal alkynes, acetylenedicarboxylates, and cyclopropylideneacetamides to produce spiro‐cyclohexadiene derivatives which retain the cyclopropane rings.     

Synthesis and Structure of trans-1,2-Bisaromatic Heterocycle Substituted Cyclopropanes

Trans-1,2-bis(2'-(5 '-phenyl-1 ',3',4'-oxadiazolyl)) cyclopropane (BDCP) and its eleven substituted novel derivatives were synthesized. Besides four derivatives of l,2-bis(2'-(5'-phenyl-l ' , 3 ' , 4 ' -ox-adiazo1yl))ethane (BPDS) were also synthesized as model compounds. The crystal structure of ethyl BDCP was determined and the cyclopropane ring was found to be able to transmit conjugation between the aromatic groups directly bonding with it by studying the ultraviolet and fluorescent spectra of the above compounds.     

C11-Chirasil-Dex as chiral stationary phase in GC: enantioselective separation of cyclopropane derivatives

Chirasil-β-Dex containing an undecamethylene spacer (C11-Chirasil-Dex) was used as chiral stationary phase (CSP) in enantioselective gas chromatography (GC). The versatility of the new stationary phase in the simultaneous enantiomeric separation of a set of cyclopropane derivatives is demonstrated. The GC method provides information about the chemical yields of the cyclopropane products, enantioselectivity, substrate specifity, and catalytic activity of the chiral catalysts used in the intermolecular cyclopropanation of olefins and avoids time-consuming work-up procedures.