Diiodomethane cyclopropanation using zinc carbenoids

A cyclopropanation of an alkene using the carbenoid reagent generated from diiodomethane and the zinc-copper couple, (p. 358)... 

Because of these and other useful molecules containing three-membered rings, methods to make them are important as well as interesting. Most chemical syntheses of compounds containing cyclopropyl groups make use of the addition of a carbene, or carbene equivalent, to an aikene. What do we mean by carbene equivalent Usually, this is a molecule that has the potential to form a carbene, though it may not actually react via a carbene intermediate. One such example is a zinc carbenoid formed when diiodomethane is reacted with zinc metal it reacts with alkenes just as a carbene would—it undergoes addition to the 7t bond and produces a cyclopropane. 

A number of modifications of the original Simmons-Smith cyclopropanation procedure have been reported. Furukawa s reagent, (iodomethyl)zinc derived from diethylzinc and diiodomethane, ° or its modification using chloroiodomethane instead of diiodomethane, ° allows more flexibility in the choice of solvent. The reagent is homogeneous and the cyclopropanation of olefins can be carried out in non-complexing solvents, such as dichloromethane or 1,2-dichloroethane, which greatly increase the reactivity of the zinc carbenoids. 

Although the Simmons-Smith reaction has found considerable use in organic synthesis, it is not readily applicable to the formation of highly substituted cyclopropanes, since 1,1 -diiodoalkanes (other than diiodomethane) are not readily available. Substituted zinc carbenoids can be prepared from aryl or a,p-unsaturated aldehydes (or ketones) with zinc metal, and these species can be trapped with an alkene to give substituted cyclopropanes.The addition of chromium carbenes (see Section 1.2.2) to alkenes can be used to effect cyclopropanation to give substituted cyclopropanes. Thus, addition of excess 1-hexene to the chromium carbene 113 gave the cyclopropane 114 as a mixture of diastereomers, with the isomer 114 predominating (4.92). ... 

Non functionalized alkenes undergo cyclopropanation with diazomethane/Pd(n) if they are strainedt or tenninal substituted. Consequently, carbene transfer to alkenyl substituted cyclohexenes occurs highly regioselective, contrasting the reactivity of such derivatives towards cyclopropanation using diiodomethane/zinc or metal carbenoids (Table 5). 

A useful cyclopropane synthesis was developed by H. E. Simmons and R. D. Smith of the DuPont Company. In this synthesis diiodomethane and a zinc-copper couple are stirred together with an alkene. The diiodomethane and zinc react to produce a carbene-like species called a carbenoid ... 

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. 

The rhodium chemistry just presented actually involves C=Rh species rather than a free carbene. In this section, we will look at a general class of compounds called carbenoids. A carbenoid is a reactive intermediate that reacts similarly to a carbene but does not actually involve formation of a carbene. The most commonly used carbenoid is generated by reaction of diiodomethane and a Zn/Cu couple this reaction, when it adds to alkenes, is called the Simmons-Smith reaction.316 A simple example is the conversion of cyclohexene to bicyclo[4.1.0]heptane (norcarane, 336). Initial reaction of diiodomethane with zinc gave an iodozinc compound (399-see sec. 9.8.B for a brief discussion of organozinc compounds), which added to the alkene to give 400. Loss of zinc iodide (Znl2) gave the cyclopropane derivative (343 in this case).3ll A one-step... 

In another route to cyclopropanes, diiodomethane is treated with zinc powder (usually activated with copper) to generate ICH2ZnI, called the Simmons-Smith reagent This species is an example of a carbenoid, or carbene-like substance, because, like carbenes, it also converts alkenes into cyclopropanes stereospecifically. Use of the Simmons-Smith reagent in cyclopropane synthesis avoids the hazards associated with diazomethane preparation. 

In Summary Diazomethane is a useful synthetic intermediate as a methylene source for forming cyclopropanes from alkenes. Halogenated carbenes, which are formed by dehydro-halogenation of halomethanes, and the Simmons-Smith reagent, a carbenoid arising from the reaction of diiodomethane with zinc, also convert alkenes into cyclopropanes. Additions of carbenes to alkenes differ from other addition processes because a single carbon atom becomes bonded to both alkene carbons. 

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