Cyclopropane 1.2- dicarboxylate, dimethyl

Dimethyl cyclopropane dicarboxylic acid anhydride procymidone Dimethyl formamide chlordimeform, formetanate... 

A carbonyl function in the a-position relative to the cyclopropane ring renders the adjacent endocyclic bond susceptible to cleavage by nucleophiles. The reactivity can be greatly increased when the polarity of the carbonyl group is enhanced by the addition of electrophiles such as protons or Lewis acids. This is exemplified by the reaction of cyclopropane dicarboxylic acid (2a) with sulfuric acid which leads to (2-hydroxyethyl)malonic acid (3a) if water is present. In a similar fashion, 2-phenylcyclopropane-l, 1-dicarboxylate (2b) gives dimethyl (2-methoxy-2-phenylethyl)malonate (3b) when treated with sulfuric acid in methanol. ... 

Cyclopropanation ([2 +1] Cycloaddition). Cu - and Rh -catalyzed cyclopropanation of olefins with dimethyldiazo malonate was used efficiently for the preparation of cyclopropane dicarboxylates. Methylenecyclopropanes were employed in this reaction to afford bicyclopentane derivatives in moderate yields and high diastereoselectivity (eq 17). Utilization of dimethyl diazomalonate in enantioselective cyclopropanation is a very challenging task. Thus the highest ee s obtained in the presence of Rh2(45-MEAZ)4 did not exceed 50% (eq 18). Cyclopropanation of olefins was also performed in the presence of catalytic amounts of copper(II) and osmium(II). ... 

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis296"300. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported298. The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-tm-butyl malonate, their preparations in satisfactory yields are realized (equation 134)297. The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135)301. Asymmetric synthesis... 

Successive treatment of (-(-dimethyl succinate with LiTMP and bromochloromethane provides (S, S)-trans-cyclopropane-1,2-dicarboxylic ester in 99% de (equation 145)324. 

Radical iodine atom transfer [3 + 2]-cycloaddition with alkene (118) using dimethyl 2-(iodomethyl)cyclopropane-l,l-dicarboxylate (117) forms cyclopentane derivative (119), through the formation of an electron-deficient homoallyl radical, followed by the addition to alkene, and cyclization via 5-exo-trig manner as shown in eq. 4.41. 

Asymmetric synthesis of cyclopropanes, The reaction of dimethyloxosnifonium methylide with (E)-(2R,3S)-6-alkylidene-3,4-dimethyl-2-phenylperhydro-l,4-oxazepine-5,7-diones (1) yields cyclopropane derivatives (2) and dihydrofuranes (3). The ratio of the products depends on the solvent and temperature. Use of THF at 25° favors formation of 2, whereas formation of 3 is favored by use of DMF at -61°. The products (2 and 3) can be converted into optically pure cyclopropane-1,1-dicarboxylic acids (4) and 3-substituted y-butyrolactones (5), respectively. 

The repeatedly noted ring-opening of ionized cyclopropane derivatives (Section III.A) seems also to account for the randomization of methoxy groups in ionized dimethyl 2-methoxy-3,3-dimethylcyclopropane-l,l-dicarboxylate. Similarly, the electron impact and chemical ionization mass spectra of benzoylcyclopropanes can be interpreted by ring-opening followed by facile 1,2-hydrogen migration, which precede the main dissociations... 

Dimethyl 3-(2-methyl-l-propenyl)-2,2-dimethylcyclopropane-l,l-dicarboxylate (324) is synthesized by the reaction of (2-halo-2-methylpropylidene)malonate (291) with 2-methyl-l-propenylmagnesium bromide (323). The cyclopropane is accompanied by the malonoester (325) and a butanolide (326) formed by nucleophilic attack of an ester enolate (equation 101) . ... 

Back in 1929 Fichter and Spiegelberg electrolyzed sodium methyl ci5-cyclopropane-1,2-dicarboxylate in MeOH and in H2O. In each case they obtained a low yield of an ester corresponding to the Kolbe-coupled product. Their suggested structural assignment for the ester was apparently wrong since others reinvestigated the reaction and found the ester to be dimethyl biscyclopropyl-2,2 -dicarboxylate (45), among other products. 

In contrast to the preceding intramolecular reactions, only a few intermolecular examples leading to bicyclo[l. 1. OJbutanes by carbene addition to cyclopropanes have been reported. Copper-catalyzed procedures generally require relatively high temperatures and yield mixtures of exo,exo-, endo.exo- and endo,endo- somtr% when 3-substituted cyclopropenes are used as reactants. Methyl 2,3-dipropylcycloprop-2-ene-l-carboxylate (8) provides the isomeric dimethyl l,3-dipropylbicyclo[1.1.0]butane-2,4-dicarboxylates (9) as a mixture (bp 90 100°C/0.5 Torr) that can be separated by preparative GC. The ejico,exo-isomer 9A is the major product. No yield is given. 

Dimethyl l,2-ri ans-3-(2-Methylprop-l-enyl)cyclopropane-l,2-dicarboxylate(23a,R =R = R = Me) Typical Procedure for 2- -1] Cycloaddition of 3,3-Dimethylcyclopropene and Electron-Poor Alkenes ... 

The same carbene can also be generated by thermolysis of 2,2-diphenyl-5-diphenyl-methylene-2,5-dihydro-l,3,4-oxadiazole. When the reaction was carried out in the presence of either dimethyl ( )-but-2-enedioate or dimethyl (Z)-but-2-enedioate one cyclopropane, dimethyl 3,3-diphenylcyclopropane-tranj-l,2-dicarboxylate (1), was formed, most likely via a 4,5-dihydro-3//-pyrazole intermediate. ... 

Obtained from active methylene compounds, such as malonic esters, -0x0 esters and jS-oxo sulfones, iodonium ylides serve as precursors of the corresponding carbenes. Their decomposition by a catalytic amount of a copper salt in the presence of a C-C double bond has been used for inter- and intramolecular cyclopropanation reactions. Thus, reaction of cyclohexene with bis(methoxycarbonyl)methylene(phenyl)iodine(III) under the catalytic action of bis(acetylacetonato)copper(II) yielded dimethyl bicyclo[4.1.0]heptane-7,7-dicarboxylate (1) (38%, mp 91-93°C) in addition to tetrakis(methoxycarbonyl)ethene (41%). ... 

The product of thermal isomerization of this cyclopropane, dimethyl (l-naphthyl)malonate, was also formed (5-10%), together withtetramethyl2,3-benzo-ant -tricyclo[5.1.0.0 ]oct-2-ene-5,5,8,8-tetracarb-oxylate (5-15%) and dimethyl 377-benzocycloheptatriene-3,3-dicarboxylate (5-10%) which is likely to arise from an intermediate cyclopropane arising from carbene addition to the 2,3-bond of naphthalene. 

Catalytic cyclopropanation of alkenes with diazomalonates is sometimes carried out with copper powder, but it appears that copper(I) halide/trialkyl phosphite complexes (for a procedure see Houben-Weyl Vol. E19b, p 1113), bis(acetylacetonato)copper(II), " ° and tet-raacetatodirhodium can be employed more advantageously (Table 13, entries 7-9). For the cyclopropanation of styrene with dicyclohexyl diazomalonate, however, copper(I) triflate was the catalyst of choice, while intramolecular C —H insertion at the cyclohexyl ring took place in the presence of tetraacetatodirhodium. A detailed comparison of copper catalysts for the cyclopropanation of cyclohexene, 1-methyl- and 1,2-dimethylcyclohexene, (Z)- and ( )-hept-2-ene with dimethyl diazomalonate, including competitive reaction pathways such as allylic C-H insertion and carbene dimer formation, is available. The catalyzed interaction between diazomalonic esters and enol ethers leads to cyclopropanes in some cases (e.g. ethoxymethylenecyclohexane to dimethyl 2-ethoxyspiro[2.5]octane-l,l-dicarboxylate ) and to different products in other cases (e.g. 1-methoxycyclohexene, 2-methoxy-3,4-dihydro-2/7-pyran ). This behavior is attributed to the occurence of stabilized dipolar intermediates in these reactions. 

The rhodium- or copper-catalyzed interaction of dimethyl diazomalonate with 2-(l-al-kenyl)thiophenes yields either a dimethyl 2-(2-thienyl)cyclopropane-l,l-dicarboxylate, a thiophenium ylide, or a dimethyl [5-(l-alkenyl)-2-thienyl]malonate, depending on the substituents at the alkene bond and the heterocyele. ... 

Tricarbonyliron complexes of conjugated trienes react with diazoalkanes at the free (uncom-plexed) double bond. In the synthesis of dimethyl 2-formylcyclopropane-l, 1-dicarboxylate (48), the ceric ion served the double function of catalyzing the deazetization and removing the tricarbonyl iron protecting group. When the optically active iron carbonyl complex was used, the addition of diazomethane gave selectively one diastereomer and this was used to make optically active dimethyl 2-formylcyclopropane-l,1-dicarboxylate (>90% ee). A similar route was employed to make the optically active formyl cyclopropanes 49, precursors to optically active cis- and tran.v-chrysanthemic acids. 

Zinc in a protic solvent has also been applied to the reductive ring opening of activated cyclopropane derivatives. Usually the most activated cyclopropyl bond was cleaved. Treatment of arylcyclopropyl aryl ketones 7 with zinc in ethanol alforded aryl propyl ketones in excellent yields. The reduction of 1,2-dibenzoylcyclopropane (7f) with zinc/zinc(II) chloride produced 1,3-dibenzoylpropane (81) in quantitative yield. Dimethyl 2-benzoyl-3-phenylcyclop-ropane-l,l-dicarboxylate (7e) was converted to the corresponding (2-benzoyl-1-phenylethyl)malonate (8e) when heated with zinc in methanol. ... 

Benzenesulfanyl chloride adds across one of the cyclopropane bonds of dimethyl tetracyclo-[3.2.0.0 . 0" ]heptane-l,5-dicarboxylate (14, = Me) to produce a 50 50 mixture of... 

An interesting reaction with the simultaneous opening of a cyclopropane and a cyclobutane ring was observed when sodium methoxide was added to dimethyl 2-(l-methyl-2-oxo-cyclobutyl)cyclopropane-l,l-dicarboxylate (19).The formation of the alkenes 20 by the fragmentation process occurred in high yield and stereospecificity. 

Potent nucleophiles can be generated from C-H acidic compounds by deprotonation. Diethyl malonate reacted with diethyl cyclopropane-1,1-dicarboxylate (1) in the presence of sodium ethoxide to give tetraethyl butane-1,1,4,4-tetraoate (2). Isopropylidene cyelo-propanedicarboxylate (3) underwent an analogous reaction when treated with dimethyl malonate or methyl 2-oxocyclohexanecarboxylate. ... 

The selectivity for the alkene-substituted cycloadduct is also almost complete in the case of the reaction of l-methylene-2-(trimethylsilyl)cyclopropane (5) with dimethyl fumarate, which results in a 78% yield of dimethyl /ra x-4-(trimethylsilylmethylene)cyclopentane-l,2-di-carboxylate (7). Interestingly, only one of the stereoisomeric dimethyl 4-methylene-3-(trimethyl-silyl)cyclopentane-l,2-dicarboxylates [the (/ , / , / )-isomer 8] is formed selectively. ... 

The formation of furans as byproducts during photolysis of dimethyl benzocyclopropene-1,1 -di-carboxylates is mentioned in Section 4.1. These furans 1 were also obtained when the ben-zocyclopropenes were heated above their melting point. The reaction proceeds by thermolysis of the cyclopropane bond to a biradical, which is intercepted by one of the carboxylate groups. Furan formation also occurred when methyl 1-methylbenzocyclopropene-l-carboxylate was thermolyzed. By analogy, heating of 2,3,4,5-tetraphenylbenzocyclopropene-1,1-dicarboxylate in quinoline afforded the decarboxylated product, 4,5,6,7-tetraphenylben-zofuran-2(3//)-one (2). ... 

The Lewis acid-promoted reactions of l-seleno-2-silylethene with a-enones and 1-phosphonoacrylates give cyclopropane products (Scheme 10.203) [534]. The [24-1] cycloaddition would proceed via 1,2-silyl migration of a-seleno-/ -silylcarbenium ion intermediate 146 and subsequent ring-closure. Interestingly, dimethyl 1,1-di-cyanoethene-2,2-dicarboxylate, a highly electron-deficient alkene, undergoes [24-2] cycloaddition under similar conditions [535]. 

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