Cyclopropane derivatives solvolysis

The generation of the dichloromethane under phase-transfer conditions may be facilitated by the addition of a trace of ethanol. Alkoxide anions, generated under the basic conditions, are more readily transferred across the two-phase interface than are hydroxide ions (see Chapter 1). Although this process may result in the increased solvolysis of the chloroform, it also produces a higher concentration of the carbene in the organic phase and thereby increases the rate of formation of the cyclopropane derivatives from reactive alkenes. 

Displacement reactions on 1,1-disubstituted cyclopropanes have been used to prepare other cyclopropanone equivalents. The most readily available 1,1-disubstituted cyclopropanes are geminal dihalo derivatives prepared by the addition of dihalocarbenes to olefins. Unfortunately, these materials do not undergo direct displacement easily and therefore do not provide a general route to other cyclopropanone derivatives. Solvolysis usually leads to ring-opened products, although dibromocyclopropanes with a barrier to... 

The hydride reduction of tosyloxycyclobutanes also proceeds mainly with concomitant ring contraction providing cyclopropane derivatives related to the solvolysis products. The synthetic usefulness of this stereospecific route to three-membered rings has been illustrated by the preparation of a 1,2-disubstituted cyclopropane of known absolute configuration from an optically active tosyloxycyclobutane. 

Since in the above examples the solvolysis of cyclopropane derivatives is accompanied by rearrangement to less strained structures, the comparison of the reactivities of compounds 392 and 567 cannot answer the question what is the relative efficiency of the participating double bond and cyclopropane ring respectively. It would be more reasonable to compare the acetolysis of the compounds 568 and 569 because their reactions are not accompanied by rearrangements... 

The results of the methanolic solvolysis study shown in Fig. 7.15 reveals that nucleophilic attack on the cyclopropyl quinone methide by methanol affords the pyrido[1,2-a]indole (73 ppm) and azepino[l,2-a]indole (29ppm) trapping products. Initially, nucleophilic attack on the cyclopropane ring affords the hydroquinone derivatives (see Scheme 7.17) that oxidizes to the quinones upon aerobic workup. 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

Artemisyl, Santolinyl, Lavandulyl, and Chrysanthemyl Derivatives.— The presence of (41) in lavender oil has been reported earlier. Poulter has published the full details of his work (Vol. 5, p. 14) on synthetic and stereochemical aspects of chrysanthemyl ester and alkoxypyridinium salt solvolyses (Vol. 3, pp. 20—22) and discussed its biosynthetic implications. Over 98% of the solvolysis products are now reported to be artemisyl derivatives which are formed from the primary cyclopropylcarbinyl ion (93) which results from predominant (86%) ionization of the antiperiplanar conformation of (21)-)V-methyl-4-pyridinium iodide the tail-to-tail product (96 0.01%) may then result from the suprafacial migration of the cyclopropane ring bond as shown stereochemically in Scheme 3. This is consistent with earlier work (Vol. 7, p. 20, ref, 214) reporting the efficient rearrangement of the cyclobutyl cation (94) to (96) and its allylic isomer, via the tertiary cyclopropylcarbinyl cation (95). ... 

The silver ion assisted carbon-halogen bond cleavage and the unraveling of the cyclopropane ring by the cyclopropyl-allyl rearrangement was first noted in the formation of 2-bromocyclohexen-l-ol from dibromobicyclo[3.l.0]hexane under solvolytic conditions (equation 86).220 The silver ion assisted solvolysis of the dihalocyclopropane adduct (43), derived from a Birch reduction product, smoothly rearranges to the tropone (equation 87).221 A number of other synthetic applications222-226 have beien reported... 

The only products of solvolysis of the tosylate 60 from the 1 -ethynylcyclopropanol 9, with R = CH3 was the allyl derivatives 61 (R = CH3) from the ring opening of the cyclopropane ring, while unrearranged cyclopropanols (or derivatives) 62 were obtained in high yields when R = cyclopropyl or aryl, Eq. (18)13>. 

A remarkable dependence of the reactivity on ring size has been found in the series of methylenecycloalkanes (Fig. 9) [106]. The exceptionally low rate constant for methylenecyclopropane indicates that the low solvolysis rates of cyclopropyl derivatives [154] are not only caused by the unfavorable change of hybridization of one ring carbon in cyclopropane but also by the low stability of the cyclopropyl cation relative to a compound with the same hybridization (methylenecyclopropane). The destabilization of the cyclopropyl cation must actually be greater than indicated by the numbers in Fig. 9 as the transition state of the electrophilic attack may already profit from the stabilizing ring-opening process (cf., Section III.B.2). 

As an alternative to a radical chain mechanism for this bromination, a cationic mechanism has been proposed for the reaction between 48 and A-bromosuccinimide. It involves attack of bromine at C6 of 48 leading ultimately to the cyclopropylmethyl cation A. This cation is a bromo derivative of tricyclic cyclopropylmethyl cation, which has been shown to be the common intermediate in the solvolysis of esters of tricyclo[3.2.1.0 ]octan-3-ol, endo- and exo-tricyclo[3.2.1.0 ]octan-4-ol and of cxo-bicyclo[3.2.1]oct-2-en-7-ol. It has been shown that under long-lived ion conditions at — 78 C such cations are the most stable species that are formed from bicyclo[3.2.1]oct-2-en-3-ol and from bicyclo[3.2.1]octa-2,6-dienes. In kinetically controlled reactions, which are postulated to proceed via cyclopropylmethyl cations a tendency can be seen towards formation of products retaining the cyclopropane ring. This case is achieved through loss of one of the protons at C4 of A. 

In the system at hand, diosgenin (7-2) is first converted to its 3-toluenesulfonate 10-1 by reaction with /i-toluenesulfonyl chloride (Scheme 2.10). Solvolysis of this compound under weakly acidic conditions leads to displacement of the excellent leaving group / -toluenesulfonate and formation of the cyclopropane-containing derivative 10-2. The newly formed hydroxyl group is next oxidized with chromium trioxide to give the 6-ketone... 

The 4 -R substituent turned out to exert absolutely equal effects in the solvolysis of both derivatives of 572 and 247. All these data support the steric reason for the accelerating effect of the exo-cyclopropane ring. Accordingly the increased reactivity of exo-brosylate 564 in comparison with the endo isomer 566 (see above) is most probably caused by the steric acceleration due to the proximity of the OBs and CHj groups. 

Attempted generation of a dicarbocation from (363 R = Me) leads only to (364) or ring-cleaved cations. However, (363 R = Ph) readily gives rise to (365) and thus the cyclopropane ring, of itself offers insufficient stabilization for these species. " Solvolysis of the tosylate (366 R = Me) results in almost quantitative cyclopropyl-allyl rearrangement. However, with (366 R = Ph or cyclopropyl) mesomeric stabilization of the cation intermediate results in ca. 90% of products derived from the unopened ion. ... 

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