Simmons-Smith cyclopropanation regioselectivity

The Simmons-Smith cyclopropanation method has also found application for the a-methylation of ketones via an intermediate cyclopropane. The starting ketone—e.g. cyclohexanone 9—is first converted into an enol ether 10. Cyclopropanation of 10 leads to an alkoxynorcarane 11, which on regioselective hydrolytic cleavage of the three-membered ring leads to the semiketal 12 as intermediate, and finally yields the a-methylated ketone 13 ... 

Cyclopropanation of unsaturated alcohols.1 The reaction of perillyl alcohol (1) with this reagent results in regioselective cyclopropanation of the isolated double bond and is therefore complementary to the regioselectivity of the Simmons-Smith reaction. The actual reagent is probably diisobutyl(iodomethyl)aluminum. 

Simmons-Smith regioselective cyclopropanation of a-enone alkyl enol ethers also provided 1-alkoxyvinylcyclopropanes in high yields43 . 

The organoaluminum-mediated cyclopropanation had unique selectivity not observable in Simmons-Smith type reactions [95], Treatment of geraniol with i-Bu3Al (2 equiv.)-methylene iodide (1 equiv.) in CH2CI2 at room temperature for 5 h produced cyclopropanation products in 75 % combined yields in the ratio 76 1 4. Consequently, methylene transfer by the aluminum method occurs almost exclusively at the C(6)-C(7) olefinic site far from the hydroxy group of geraniol and the C(2) -C(3) ole-finic bond was left intact. In sharp contrast, the zinc method resulted in the opposite regioselectivity via hydroxy-assisted cyclopropanation, as shown in Sch, 62. 

The fact that the Simmons-Smith reaction is regio- and stereoselective enabled the preparation of tritium containing cyclopropane derivatives useful for biological studies. The tritiated diiodomethane was prepared by reduction of iodoform with sodium arsenite in the presence of tritiated water. The carbene generated from tritiodiiodomethane and triisobutylaluminum in chloroform underwent regioselective addition to the unhindered double bond in perillyl alcohol (34). ... 

The electron-deficient double bond in 2-phenylsulfonyI-l,3-dienes underwent regioselective cyclopropanation with sulfur ylides in very good yield, e.g. cyclopropanation of 13, 14 and 15 with sulfur ylides.On the other hand, the use of zinc-copper couple and diiodomethane afforded a 83 17 mixture of vinylcyclopropanes 16 and 17 from 2-(phenylsulfonyl)cyclohexa-1,3-diene (15) in moderate yield. The reaction at the electron-deficient double bond rather than at the expected electron-rich double bond shows that the Simmons-Smith carbenoid is fairly nucleophilic in character. 

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). 

The use of a trialkylaluminium-alkylidene iodide mixture to effect cyclopropanation has been re-examined. The reaction was found to work well when conducted in CH2CI2, and shows contrasting regioselectivity to the Simmons-Smith reagent in reaction with geraniol (Scheme 2). 

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