Simmons-Smith cyclopropanation mechanism

This study suggests a radically new explanation for the nature of Lewis acid activation in the Simmons-Smith cyclopropanation. The five-centered migration of the halide ion from the chloromethylzinc group to zinc chloride as shown in TS2 and TS4 has never been considered in the discussion of a mechanism for this reaction. It remains to be seen if some experimental support can be found for this unconventional hypothesis. The small energy differences between all these competing transition states demand caution in declaring any concrete conclusions. 

Some of the evidence for this comes from a reaction that not only throws light on to the mechanism of Simmons-Smith cyclopropanations, but makes them of even greater value in synthesis. When an allylic alcohol is cyclopropanated, the new methylene group adds stereoselectively to the same face of the double bond as the alcohol group. 

Simmons-Smith reagent Named after the duPont chemists who discovered that diiodo-mechane would react with an active zinc-copper couple in ether to give a reagent with molecular formula ICHiZnl. The reagent adds stereospecifically cis- to alkenes to give cyclopropanes in high yields. 

Bernardi and co-workers investigated the mechanism of the Simmons-Smith reaction theoretically at the DFT (B3LYP) level of theory, using ClCH2ZnCl as a model system.95 Of the two available reaction channels (addition and insertion), the former process was found to have the lower activation energy (107.7 vs. 150.7 kj moP1), and this result correlates well with the exclusive cyclopropanation over the competing insertion reaction. 

The mechanism for the formation of this carbenoid and for its reaction with alkenes need not concern us here. Just remember that it reacts as though it is methylene. The Simmons-Smith reaction is an excellent way to prepare cyclopropane derivatives from alkenes, as shown in the following examples. Note the stereochemistry in the second equation. 

A cis addition mechanism is generally accepted for the reaction, because cis addition to an olefinic bond generally occurs with predominant attack at trans bonds, and the Simmons-Smith reagent attacks preferentially one of the trans olefinic bonds of trans,trans,cis-1,5,9-cyclodode-catriene and then the cis double bond of the monoadduct (378). The close correspondence in relative rates of olefins for the cyclopropane formation by the Simmons-Smith reaction with those for diimide reduction and peroxide epoxidation supports the concept 409). The latter two reactions are generally considered to proceed via cis addition. 

No matter how they are generated, carbenes and carbenoids undergo four typical reactions. The most widely used reaction is cyclopropanation, or addition to a TT bond. The mechanism is a concerted [2 + 1] cycloaddition (see Chapter 4). The carbenes derived from chloroform and bromoform can be used to add CX2 to a 7T bond to give a dihalocyclopropane, while the Simmons-Smith reagent adds CH2. Carbenoids generated from diazoalkanes with catalytic Rh(II) or Cu(II) also undergo cyclopropanations. 

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. 

A modified version of the Simmons-Smith reaction uses dibromomethane and in situ generation of the Cu-Zn couple. Sonication is used in this procedure to promote reaction at the metal surface. Cyclopropanation can also be affected with a combination of CH2I2 and an alkylzinc reagent. The reaction is stereospecific and strongly regioselective. Thus, it has been found that cyclopentenol gives only the mdo-bicyclic alcohol (Scheme 5.34). The mechanism of the Simmons-Smith reaction appears to be carbene transfer from the metal to the alkene without any free carbene being released (Scheme 5.35). 

Cyclopropanation of alkenes with the Simmons-Smith reagent bears some similarity to epoxidation. Both reactions are stereospecific cycloadditions, and iodomethylzinc iodide behaves, like peroxy acids, as a weak electrophile. Both cycloadditions take place faster with more highly substituted double bonds than less substituted ones, but are sensitive to steric hindrance in the alkene. These similarities are reflected in the mechanisms proposed for the two reactions shown in Mechanism 14.2. Both are believed to be concerted. 

Simmons-Smith reaction Areactionin which a cyclopropane ring is produced from an alkene. It uses the Simmons-Smlth recent, which was originally diiodo-methane (CH2I2) with aZn/Cu couple. Usually, diethyl zinc is used rather than Zn/Cu. The mechanism involves the formation of H2C(I) (Znl) and carbene transfer from the zinc to the double bond of the alkene. 

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