Zinc carbenoids alkene cyclopropanation

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. 

Functionalized zinc carbenoids have been prepared from carbonyl compounds by an indirect strategy. The deoxygenation of a carbonyl compound to an organozinc carbenoid can be induced by a reaction with zinc and TMSCl. Therefore, the aldehyde or ketone, when treated with TMSCl or l,2-bis(chlorodimethylsilyl)ethane in the presence of an alkene, generates the cyclopropanation product. This method is quite effective for the production of alkoxy-substituted cyclopropane derivatives. A 55% yield of the... 

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

Since the cyclopropanation reaction nsing zinc carbenoids is nsnally faster with electron-rich alkenes, it is not surprising to observe that enol ethers are nicely converted into cyclopropyl ethers in high yields (equation 17). ... 

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. 

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 stereoselective cyclopropanation of chiral alkenes can be divided into two classes cyclic and acyclic alkenes. Furthermore, within each class, a subdivision exists involving those that contain a proximal basic group that can direct the cyclopropanation reaction of zinc carbenoids and the others that do not. The discrimination of reactivity between alkenes that possess a proximal basic group and those that do not was first highhghted early on when Simmons and Smith noticed that the cyclopropanation of l-(o-methoxyphenyl)-l-propene was more efficient than that of the related meta and para isomers (equation 46). ... 

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. 

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. 

On the subject of stereochemistry, note that the Simmons-Smith zinc carbenoid behaves like a singlet carbene— its additions to alkenes are stereospecffic (the product cyclopropane retains the geometry of the aikene) as well as stereos elective (die carbenoid adds to the same face as the hydroxyl group). 

Synthesis of model compounds and structural units are being investigated. A double Simmons-Smith reaction on the l,3-dioxolane-4,5-diylbis(alkene) 107 afforded the product 108 with excellent stereoselectivity. The required asymmetry in the double cyclopropanation was the result of coordination of the zinc carbenoid reagent by the Lewis basic dioxolane ring oxygen prior to each cyclopropanation event. The cyclopropanated product was converted to ( )-l,2-bis[(l 5,25)-2-methylcyclopropyl]ethene, a relevant model for the complete structural assignment of FR-900848. 

Two types of cyclization reaction take place when a ketene silyl acetal is treated with a carbenoid generated from CHBrs and ZnEt2. ° When the substrate is aliphatic (Scheme 7), a cyclopropylcarboxy-late is formed due to a CH insertion reaction of an intermediate zinc carbenoid. With substrates having an alkene in the vicinity of the carbenoid (Scheme 7), in particular those derived from 8,e-unsaturated esters, internal cyclopropanation takes place. 

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). ... 

Charette and coworkers investigated the stereoselectivity of gem-zinc carbenoids in the reaction with allylic alcohols 100 and 101 (Scheme 1.52). Configuration at the allylic stereogenic center and alkene geometry affected the stereoselectivity of cyclopropanation [87]. 

The bis(benzoyloxymethyl)zinc (71) was prepared either from zinc benzoate and diazomethane or from benzoyloxymethyl iodide and EtiZn under photolysis conditions (Scheme 9) . Such an acyloxymethylzinc compound appeared to be a reactive carbenoid capable of reacting with a variety of non-functionalized alkenes to afford cyclopropanes in excellent yields (Scheme 9). 

---