Cyclopropyl-Cope rearrangement

Twenty-one years after the discovery of the Cope rearrangement, the cyclopropanation of 1,3,5-hexatriene (38) by diazomethane in the presence of cuprous chloride resulted in the rearranged structure 40, instead of the expected cyclopropane product. In what is referred to as a divinylcyclopropane rearrangement (or cyclopropyl-Cope rearrangement), the c/5-orientation of the alkenes and the relief of cyclopropane ring strain... 

In recent years, the synthetic utility of the cyclopropyl-Cope rearrangement has expanded exponentially as a result of new chiral organometallic catalysts which allow for the efficient, stereoselective formation of the required cw-divinylcyclopropanes. " One of the leaders in this area is Davies, who has repeatedly demonstrated the successful tandem cyclopropanation/Cope rearrangement between vinyldiazoacetates and dienes for the synthesis of functionalized seven-membered rings. 

The Stoltz group has developed a novel extension of the cyclopropyl-Cope rearrangement for the stereoselective synthesis of... 

The spectrum at — 50°C is in accord with a slow rate for the degenerate Cope rearrangement and in addition to four vinylic protons at 65.1, two allylic protons at 6 2.8, there is also a single cyclopropyl proton, 6 0.3 two tertiary cyclopropyl protons absorb between 61-2 and a second cyclopropyl proton is thought to be deshielded by the double bonds. 

Semibullvalene [44] has a very low barrier to Cope rearrangement (41) which averages C-l/C-5 and C-2,C-8/C-4,C-6 and leaves C-3 and C-7 unaffected. Below — 160°C the exchange is slow on the nmr time scale and the averaged carbon and corresponding protons signals are split, giving five resonances as expected. The carbon shift differences are 5.8 ppm and 89.6 ppm for C-l/C-5 and C-2,C-8/C-4,C-6 respectively. The cyclopropyl carbons C-1 and C-2,C-8 are shifted upheld (Anet et al., 1974). 

A slight modification of the cyclopropyl conjunctive reagent transforms a cyclopentannulation into a cycloheptannulation. Thus, the 2-vinylcyclopropyllithium reagent 3, converted to its cuprate 4, generates a 1,2-divinylcyclopropane. Heating to only 180 °C leads to smooth Cope type rearrangement, driven by the release of the cyclopropyl strain, to create a perhydroazulene ring systerh of many sesquiterpenoids (Eq. 19) 20>. 

The rearrangement exhibits some stereochemical preference for c/s-vinyl carbene complex (with respect to the metal) compared to the //ww-isomer. Thus, 2-methyl-2-m-vinyl cyclopropyl (methoxy) carbene chromium pentacarbonyl rearranges to 5-methyl-5-vinyl-2-methoxycyclopentenone approximately 4 times faster (THF, 52 °Q than the trans-isomer, which in turn rearranges faster than phenyl derivatives. This suggests that vinyl complexes undergo initial Cope-type rearrangement to form metallacycloheptadienes, which then rearrange to jt-allyl complexes. Subsequent CO insertion and reductive elimination leads to the vinylcyclopentenones (equation 89)150. 

Generally, when 1,5-dienes are heated, they isomerize in a [3,3]-sigmatropic rearrangement known as a Cope rearrangement17 (not to be confused with the Cope elimination process). The mechanism is a simple six-membered pericyclic process, the chair form being the usual transition state. However, in this case the cyclopropyl moiety forces the geometry of the transition state into boat form 28. 

The bicyclic cyclopropyl ketone shown in equation 174—easily accessible from the corresponding diazocarbonyl compound—could be transformed into two bicyclic divinylcyclopropanes with different functionality and positioning of the cyclopentene double bond. Rearrangement of these compounds leads to the bicyclo[12.1]octane series Very recent syntheses of the terpenes sinularene and quadrone include a pivotal Cope process of divinylcyclopropanes generated and rearranged in an analogous fashion (equation 175) . 

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