Organozinc compounds cyclopropanation

Miscellaneous Reactions of Organozinc Compounds which Give Cyclopropane Derivatives from Olefins... 

The intramolecular Wurtz-type coupling of dihaloorganic compounds with use of metallic zinc is a classical synthetic route to cyclic compounds. For example, cyclopropane derivatives can be prepared from 1,3-dihalo-propanes (29, 189a, 248, 451), and cyclobutane derivatives from 1,4-dihalobutanes (71). These reactions presumably proceed via the intermediate formation of organozinc compounds. The reaction of diethylzinc with esters of a,a -dibrominated aliphatic dicarboxylic acids leads to the... 

In contrast to the polar nature of C-Li and C-MgX bonds, the C-Zn bond is highly covalent and hence less reactive, allowing the preparation of functionalized derivatives. Utilization of organozinc reagents in organic synthesis has mainly centered around the preparation and utilization of functional organozinc compounds in organic syntheses (Reformatsky reaction), cyclopropanation (Simmons-Smith reaction), and transmetalations with transition metals. 

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... 

The first reaction is a variation on Simmons-Smith cyclopropanation. Though strictly a carbenoid rather than a carbene, it delivers a CH2 group from an organozinc compound bound to an oxygen atom, in this case the OMe group. Only that alkene reacts. 

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

Organometallic Methods. The use of the Simmons-Smith reaction and of organozinc compounds in synthesis has been reviewed.Cyclopropanation of steroids is frequently carried out by treatment with methylene iodide and a zinc-copper couple, although yields and/or stereoselectivity are often poor. Other routine applications... 

The Simmons-Smith Reaction (Section 15.3C) Treatment of CHjIj with a zinc-copper couple generates an organozinc compound, known as the Simmons-Smith reagent, which reacts with alkenes to give cyclopropanes. 

Organozinc compounds, XZnCRR (RR = H, alkyl, X halogen), are widely used for the synthesis of cyclopropanes as Simmon-Smith reagents [12,36,37,79- 93]. Simmon-Smith reagents are prepared by two processes as shown in eqs. (5.32) and (5.53). The first one is the reaction of diazomethane with zinc halides. The second is the reaction of methylene iodide with an activated zinc. Zinc containing 10% of... 

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... 

Bis(alk-2-enyl)zinc compounds 12, on addition to 3,3-dimethylcyclopropene, yield more than 90% of organozinc addition compounds 13 that can, by acidolysis, be converted into substituted cyclopropanes. Depending on the substitution pattern of the starting material, the reaction can be seen to proceed with allylic inversion. In contrast to addition reactions with unstrained double bonds, the reaction proceeds smoothly at — 20 to — 5 °C. Diethyl ether or tetrahy-drofuran can be employed as solvent and the cA-addition products are formed stereoselectively and in high yield. 

Organozinc carbenoids generated from aryl and a,)8-unsaturated carbonyl compounds by treatment with zinc and l,2-bis(chlorodimethylsilyl)ethane have been trapped with alkenes to give cyclopropanes. The reaction is limited as it cannot be applied to all carbonyl compounds in general examples are the formation of 25 and 26. ... 

Organozinc reagents are less nucleophilic than organomagnesium compounds and can be easily prepared with a variety of functional groups (see Chapter 7), several of them were tested for the reductive cyclopropanation of amides. Therefore, a new protocol was devised for the efficient preparation of various tert-butoxycar-bonyl and chloroalkylsubstituted cydopropylamine derivatives (Scheme 12.50) [70]. 

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