Reactions of Methylene Cyclopropanes

Shi and coworkers have reported that among other Lewis acids, Bp3 OEt2 can promote the nucleophilic attack of alcohols on methylene cyclopropanes to give the corresponding homoallylic ethers such as (145) in good yield (Equation 87) [89]. 

Along the same lines, Kilburn and coworkers have shown that BF3 AcOH, a mild Lewis acid, is able to promote the cascade cyclization of trimethylsilyl-substituted methylene cyclopropyl ketone (146) to afford the oxabicyclic compound (147) through the intermediacy of the allyl cation (148) (Equation 88) [90]. 

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According to the data in Table 3 the reactivity of methylenecyelopropanes should lie somewhere between that of norbomene and a cyclopropene. In practice, the situation is even more complex (and sometimes puzzling) because there are three different strained bonds within a methylenecyclopropane C(l)-C(4), C(2)-(3) and C(l)-C(3). Moreover, little is known about the strain energies of the organo-metallic intermediates involved in transition metal catalyzed reactions of methylene-cyclopropanes. 

The product selectivity in the reaction of methylene cyclopropanes with alkynes is strongly substituent-dependent the reaction is catalysed by Ni(0)/tris(o-tolyl Iphosphite (eqn.47). The intramolecular hydroacylation of 4-pentenal is catalysed by low valent Co/PPh3 complexes and produces mainly cyclopentanone.Cyclopentenones and cyclohexenones are the products of the intramolecular carbonylation of vinyl iodides (eqn.48). A large variety of heterocycles are accessible the intramolecular Pd catalysed cyclisation of unsaturated a-haloamides. Treatment with base and PdfOAclj/PPhj converts 2,6-dibromo-l,6-dienes into cyclopentanes with exocyclic double... 

Cyelobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,s (3) ozonolysis of methylenecyclobutane, (4) epoxidation of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(co-chloropropyl)-l,3-dithiane.8... 

If small amounts of PhSSPh were deliberately added from the beginning, the more positive reduction potential could be applied from the start. Indirect electrochemical eliminations were also performed in the case of 1,2-dihalides Ringopening reactions by the redox catalytic method were possible in the case of methylene cyclopropanes and epoxides... 

Butadiene. The reaction of methylene with butadiene was studied by Frey44 under experimental conditions similar to those in the case of allene, except that lower pressures were required to avoid butadiene polymerization. Products formed by attack of methylene on the C—H bonds were cis and vinyl-cyclopropane resulting from addition of CH2 to the carbon-carbon double bond underwent collisional deactivation or isomerization to cyclopentene and C dienes, with the exception of isoprene. 

Bestmann and Seng (5) reported that the reaction of methylene triphenylphosphorane with crotonic ester gave a cyclopropane derivative. We found that the less active carbomethoxymethylene triphenylphosphorane did not react with crotonic ester at all. 

Similarly, the reactions of methylene with saturated compounds and hydrogen require postulation of excited products to explain the kinetics98-100. The production of excited methyl cyclopropane... 

The application of both criteria to gas-phase reactions is complicated further by the formation of vibrationally excited products. Both the insertion and addition reactions of methylene are exothermic by approximately 93 kcal. mole (based on recent estimates of AH (CH2) = 94 kcal.mole" ). Vibrationally excited alkanes and alkenes may dissociate into free radicals, and excited cyclopropanes may undergo structural and geometrical isomerizations unless collisionally stabilized . The occurrence of hot molecule reactions excludes any reasonable estimation of singlet and triplet methylene fractions. The data presented in the following paragraphs have been taken from experiments at high-pressures", which are thought to ensure complete collisional deactivation of excited reaction products. 

Organozinc compounds, XZnCRR (RR = H, alkyl, X halogen), are widely used for the synthesis of cyclopropanes as Simmon-Smith reagents [12,36,37,79- 93]. Simmon-Smith reagents are prepared by two processes as shown in eqs. (5.32) and (5.53). The first one is the reaction of diazomethane with zinc halides. The second is the reaction of methylene iodide with an activated zinc. Zinc containing 10% of... 

Preparation of 2-Cyclopropylcarbony/amido-5-Chlorobenzophenone To 400.5 g (1.73 mols) of 2-amino-5-chlorobenzophenone dissolved in 220 g (2.18 mols) of triethylamine and 3.5 liters of tetrahydrofuran is added cautiously 181 g (1.73 mols) of cyclopropane-carboxylic acid chloride. The reaction is refluxed 2 /2 hours and allowed to cool to room temperature. The solvent is then removed under vacuum to obtain 2-cyclopropylcarbonyl-amido-5-chlorobenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with 10% potassium hydroxide. The methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The residue is recrystallized from 1,500 ml of methanol, charcoal-treating the hot solution to give 356 g of 2-cyclopropylcarbonylamido-5-chlorobenzophenone, MP 105° to 105.5°C (69% yield). 

D. L. Phillips, W.H. Fang, and X. Zheng, Isodiiodomethane is the methylene transfer agent in cyclopropanation reactions with olefins using ultraviolet photolysis of diiodomethane in solutions a density functional theory investigation of the reactions of isodiiodomethane, iodomethyl radical, and iodomethyl cation with ethylene. J. Am. Chem. Soc. 123(18), 4197-4203 (2001). 

Cyclopropanation with Halomethylzinc Reagents. A very effective means for conversion of alkenes to cyclopropanes by transfer of a CH2 unit involves reaction with methylene iodide and a zinc-copper couple, referred to as the Simmons-Smith reagent.169 The reactive species is iodomethylzinc iodide.170 The transfer of methylene occurs stereospecifically. Free CH2 is not an intermediate. Entries 1 to 3 in Scheme 10.9 are typical examples. 

A different result was obtained in the cycloaddition to methylenecyclo-propanes 216-218 tearing alkoxycarbonyl substituents on the cyclopropyl ring. In this instance, 1,2,3-triazoles 220 isomeric with the triazolines 219 were formed in the reaction [57]. The formation of triazoles 220 is rationalised by the intermediate formation of triazolines 219, which are unstable under the reaction conditions and undergo a rearrangement to the aromatic triazoles via a hydrogen transfer that probably occurs with the assistance of the proximal ester carbonyl (Scheme 35). The formation of triazoles 220 also confirms the regio-chemistry of the cycloaddition for the methylene unsubstituted methylene-cyclopropanes, still leaving some doubt for the substituted ones 156 and 157. 

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