Methylene transfer cyclopropane synthesis

Scheme 10.12 gives some examples of enantioselective cyclopropanations. Entry 1 uses the W.s-/-butyloxazoline (BOX) catalyst. The catalytic cyclopropanation in Entry 2 achieves both stereo- and enantioselectivity. The electronic effect of the catalysts (see p. 926) directs the alkoxy-substituted ring trans to the ester substituent (87 13 ratio), and very high enantioselectivity was observed. Entry 3 also used the /-butyl -BOX catalyst. The product was used in an enantioselective synthesis of the alkaloid quebrachamine. Entry 4 is an example of enantioselective methylene transfer using the tartrate-derived dioxaborolane catalyst (see p. 920). Entry 5 used the Rh2[5(X)-MePY]4... 

Recent examples of this type of methylene transfer are the cyclopropanation of several a, -unsaturated esters 1 with dimethyloxosulfonium methanide to afford the cyclopropanated products 2 which were used for the synthesis of cyclopropanated barbiturates. Aryl-substituted spirocyclopropanobarbiturates 4 were obtained by the reaction of 2 with urea (3). ... 

The cisjtrans ratio of the cyclopropanes formed in this transformation depends to some extent on the nature of the salts and the solvent. A particularly high cisitram ratio was obtained when copper(II) acetate, calcium chloride, and ethanol were employed (no values given). Cyclopropane synthesis from active methylene compounds and nonactivated alkenes was also possible with the help of iodine and a base under phase-transfer conditions. Intra-and intermolecular reactions to give 6 and 5, respectively, have been carried out. The intramolecular reaction is nonstereospecific with respect to the C-C double bond. Although an iodo-substituted intermediate has been isolated in one case, all the details of the reaction mechanism are not yet clear. 

Methylene iodide and a zinc-copper couple react in ether solution to give bis-(iodomethyl)zinc zinc iodide . Closely related reagents are accessible by the reaction of zinc halides with diazomethane . These reagents have been widely used in the synthesis of cyclopropanes from olefins. Norcarane formation from cyclohexene and bis(iodomethyl)zinc was found to be second order, k = (6.3 0.5) x 10 l.mole . sec " at 0°C These findings cannot be reconciled with the intermediacy of free methylene. A one-step methylene transfer mechanism has therefore been proposed for the Simmons-Smith reaction, viz. 

An interesting, and potentially useful, approach to the synthesis of optically active cyclopropanes is by the use of chiral iron complexes (XLVI) as methylene transfer agents to olefins (Davison et al, 1974). Reaction of XLVI with 1-phenyl-1-propene under acidic conditions affords (— )- lR,2R) trans-2-methylphenylcyclopropane (26% enantiomeric excess). 

Compound 1 did not react with unstimned internal olefins such as tetramethylethylene, /ra s-3-hexene, tram-stilbene, cyclooctene, cyclohexene, or cyclopentene. But imposing strain to the olefinic moiety resulted in a clean silylene transfer to the double bond Norbomene formed with 1 the tricyclic silacyclopropane 6. Whereas 2 did not add to the double bond of 7, methylene cyclopropane 8 could be transformed into spiro[2.2]pentane 9 by reaction with 1. Addition of 2 to bicyclopropylidene allowed the convenient synthesis of dispiro[2.0.2.1]heptane 10 in a quantitative manner. 

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

In a related reaction, ethyl cyanoacetate is the source of the cyano(ethoxycarbonyl)methylene unit which is transferred to alkenes by a radical mechanism, e.g. synthesis of 3. This transformation is mediated by copper(II) chloride or acetate, accompanied by lithium chloride. Synthesis of diethyl cyclopropane-1,1-dicarboxylates from diethyl malonate and alkenes is much less efficient. ... 

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