Cyclopropane from enone

Corey s seminal investigations of the chemistry of trimethylsulfoxonium ylide established a powerful method for the generation of cyclopropanes from enones [19, 21, 73, 74). In a typical experiment, treatment of enones such as carvone (121) with Me3S(0)I/NaH in DMSO leads to the formation of 122 in 82% yield as a single diastereomer (Equation 19) [74]. 

Synthesis of enones and cyclopropanes from bis(oxoalkyl)tellurium dichlorides... 

Ylides derived from the salts obtained by A. A -dialkylation of sulfoximines and anions derived from A -tosylsulfoximines are useful reagents for the synthesis of epoxides or cyclopropanes from aldehydes and ketones or enones. ... 

The key step in this sequence, achieved by exposure of 46 lo a mixture of sulfuric acid and acetic anhydride, involves opening of the cyclopropane ring by migration of a sigma bond from the quaternary center to one terminus of the former cyclo-l>ropane. This complex rearrangement, rather reminiscent of the i enone-phenol reaction, serves to both build the proper carbon. keleton and to provide ring C in the proper oxidation state. 

Replacing the epoxide by a cyclopropane, also available from an enone as in the preparation of 99 (Eq. 114), also possesses in excess of 209 kJ/mole (50 kcal/mole)... 

Starting from optically active 1-chlorovinyl p-tolyl sulfoxide derived from 2-cyclohex-enone, the asymmetric synthesis of cyclopropane derivative (85) was realized (equation 23) . Addition reaction of lithium enolate of tert-butyl acetate to 83 gave the adduct (84) in 96% yield with over 99% ee. Treatment of the latter with i-PrMgCl in a similar way as described above afforded optically pure (15,6/ )-bicyclo[4.1.0]hept-2-ene (85) in 90% yield. 

In the first attempts to use a chiral a-sulfinyi ester enolate as donor in Michael additions to a -un-saturated esters, only low selectivities were observed.185 186 Better results are obtained when the a-lithio sulfoxide (174), a chiral acyl anion equivalent, is employed. Conjugate addition of (174) to cyclopent-enone derivatives occurs with reasonably high degrees of asymmetric induction, as exemplified by the preparation of the 11-deoxy prostanoid (175 Scheme 63).187 188 Chiral oxosulfonium ylides and chiral li-thiosulfoximines can be used for the preparation of optically active cyclopropane derivatives (up to 49% ee) from a, -unsaturated carbonyl compounds.189... 

So what has this got to do with cyclopropanes If sulfur ylids react with enones either the epoxide 74 or the cyclopropane 76 may be formed.19 The general rule is that sulfonium ylids from 69 give epoxides but sulfoxonium ylids give cyclopropanes 76. 

The first catalytic asymmetric cyclopropanation using an ylide as catalyst was reported by Aggarwal et al. in 1997 [95, 96]. Phenyl diazomethane was added slowly to a mixture containing sulfide 12, an enone and Rh2(OAc)4 (1 mol%). A sulfur ylide was generated in situ from the sulfide and phenyl diazomethane in the presence of the transition-metal catalyst (see Scheme 10.20), as in the epoxidations discussed earlier (see Section 10.2.1.3). 

From Simmons-Smith Cyclopropanation of a-Enone Enol Ethers... 

Dioxins behave as masked cis y-hydroxy enones and as such are an excellent source of y-lactones, notably in an enantio-enriched form <02JOC5307>. Treatment of the dioxin with an amine base results in rearrangement to 1,4-dicarbonyl compounds from which pyrroles and thiophenes are available in a one-pot synthesis <02TL3199>. Stabilised phosphonates add to 1,2-dioxins to yield diastereo-pure substituted cyclopropanes <02JOC3142>. 

Methylene cyclopropanes are of interest as the substrate having high reactivity originated from the strained structure. The platinum-catalyzed reaction of diboron proceeded through the proximal bond cleavage of the cyclopropane ring (Equation (27)).223 Addition of diborons to enones provided 1,4-addition products in the presence... 

Why does the stabilized ylid prefer to react with the double bond In order to understand this, let s consider first the reaction of a simple, unstabilized ylid with an unsaturated ketone. The enone 1 has two electrophilic sites, but from Chapters 10 and 23, in which we discussed the regioselectivity of j attack of nucleophiles on Michael acceptors like this, you would expect that direct 1,2-attack on the i ketone is the faster reaction. This step is irreversible, and subsequent displacement of the sulfide i leaving group by the alkoxide produces an epoxide. It s unimportant whether a cyclopropane prod- uct would have been more stable ihe epoxide forms faster and is therefore the kinetic product. 

Resolved P-hydroxy sulfoximines derived from cyclic enones undergo dias-tereoselective Simmons-Smith cyclopropanation reactions to give, after thermolysis, cyclopropylketones in high enantiomeric purity (94-98%). Cyclopropanation occurs syn to the hydroxyl group of the P-hydroxy sulfoximine. This method is less diastereoselective for acyclic enones.73... 

The original approach was designed to emulate the successful cyclization of anion V to the sativene precursor VI, by means of base treatment of a closely related enone derivative. The resulting anion (Vila) from the enone, however, failed to cyclize as predicted, yielding only the cyclopropane derivative I (see Scheme 6.2). The end result was, nevertheless, equally rewarding, since structure III exactly filled the purpose for which anion Vllb was intended. 

Cyclopropane derivatives have been prepared from reactions of arsonium ylides with conjugated enones " and a, jS-unsaturated esters "" . Initial Michael-type reaction is followed by intramolecular elimination of triphenylarsine, e.g. equation 22. These reactions often give high yields and show high stereoselectivity. 

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