Alkenes cyclopropanation using zinc carbenoids

The synthesis of halo-substituted cyclopropanes using zinc carbenoids can be accomplished using three different approaches by the cyclopropanation of a halo-substituted alkene, by the cyclopropanation using a halo-substituted zinc carbenoid, or by the cyclopropanation using, gem-dizinc carbenoids followed by trapping the cyclopropylzinc with an electrophilic halide source. 

III. MECHANISM OF THE CYCLOPROPANATION OF ALKENES USING ZINC CARBENOIDS... 

The intramolecular version of the cyclopropanation of alkenes using zinc carbenoids has not been extensively studied. One major limitation is the need to prepare the precursor, since there are relatively few mild methods to generate 1,1-diiodoalkanes (equation 44) ". 

The cyclopropanation of alkenes using zinc carbenoids displays excellent chemoselec-tivities. A large number of functional groups are compatible with these reagents, such as alkynes, silanes, stannanes, germanes, alcohols, ethers, sulfonate esters, aldehydes. 

The use of iodoform as the reagent precursor under Furukawa s conditions gives rise to a more complex scenario, since the additional C—I bonds can further react with an ethylzinc species (equation 8)" . The reaction of the iodo-substituted zinc carbenoid with an alkene will generate an iodo-substituted cyclopropane, whereas that involving the gem-dizinc carbenoid will lead to a cyclopropylzinc product. The evidence for the formation of a. gem-dizinc carbenoid was obtained not only by the analysis of the cyclopropanation products but also by the formation of rfi-iodomethane upon quenching the reagent with D2O/DCI. 

However, this method really hit the headlines when it was used on allylic alcohols 61 and became known as the Simmons-Smith reaction.15 If there is stereochemistry at the alcohol 63, the cyclopropane is formed on the same side as the OH group 64 suggesting that the alcohol guides the zinc carbenoid into the alkene. 

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. 

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). 

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... 

Cyclopropanation of alkenes, in both inter- and intramolecular modes, constitutes an attractive route to polycycloalkanes. These cyclopropanations of alkenes are carried out through car bene or carbenoid intermediates . For the direct cyclopropanation of alkenes, the methylene iodide zinc-copper couple (Simmons-Smith reaction)reagent is commonly used. Several modifications of this procedure, including acceleration with ultrasound, are known °°. A somewhat less frequently used procedure for cyclopropanation is through methylene addition from diazomethane, which can be carried out either thermally or photochemically or in the presence of metal salts, e.g. Pd(OAc)2 or Rh2(OAc)4. In Table some examples of the preparation of cyclopropane bearing... 

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 ... 

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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