Bicyclo Cope rearrangement

The Cope rearrangement of hexa-l,5-diene does not allow for differentiation of starting material and product this is called a degenerate Cope rearrangement. Another example is the automerization of bicyclo[5,l,0]octa-2,5-diene 7 ... 

It was pointed out earlier that a Cope rearrangement of 1,5-hexadiene gives 1,5-hexadiene. This is a degenerate Cope rearrangement (p. 1380). Another molecule that undergoes it is bicyclo[5.1.0]octadiene (105). At room temperature the NMR... 

Another variation of valence isomerization of hexa-1,5-dienes is the [3,3] sigmatropic shift of a C — C bond (Cope rearrangement). Tor example, r/.v-bicyclo[6.1.0]nona-2,6-diene (27) isomer-izes at 60 C in one hour to give < /.v-bicyclo[5.2.0]nona-2,5-diene (28).73... 

Bicyclo[5.4.0.]undecanes. An attractive route to this ring system (2), characteristic of some sesquiterpenes, involves as the final step an oxy-Cope rearrangement of... 

Ethenolysis is synthetically very useful. The reaction of stilbene (68) with ethylene is attracting attention as a potential commercial process for styrene (65). The a,co-dienes 46 are formed from cyclic alkenes 43 and ethylene. Ethenolysis of the bicyclo[2.2.0]hexene 71, formed from 69 via 70, afforded the 1,5-diene 72, which underwent Cope rearrangement to give the cyclooctadiene 73 [24],... 

An interesting example of the transfer of center chirality to helicity is the work by Ogawa et al., based on an asymmetric aromatic oxy-Cope rearrangement to provide nonracemic [5]helicenes (Fig. 15.8) [75]. The starting material with center chirality, bicyclo[2,2,2]ketone (-)-21 (>98% ee), was obtained by enzymatic resolution. In the annelation step, the phenanthrene derivative was subjected to aromatic oxy-Cope rearrangement, to afford a pentacyclic product in 47 % yield. The corresponding [5]helicene 22 was obtained in 7 % overall yield (> 98 % ee) after six steps. 

A search for possible degenerate behavior in bicyclo[3.3.0]octa-2,6-dienes164 has not produced clear results due to structural misassignments.126 The normal Cope rearrangement of 112 can be redirected through coordination to rhodium (I) to... 

The enthalpy of activation is distinctively higher for the valence isomerization than for the Cope process. This clearly shows that the bicyclo is not an intermediate during the Cope rearrangement. The stereochemical process of the Cope rearrangement, in which the... 

The Claiscn rearrangement of allyl vinyl ethers is usually an irreversible reaction due to the energetic benefit of forming aC-O double bond. However, in strained bicyclic systems the retro-Claisen rearrangement (3-oxa-Cope rearrangement) of y,<5-unsaturated aldehydes has been observed32. Sometimes equilibrium mixtures of vinyl ether and carbonyl compound were found. For example, the ratio of the valence tautomers, bicyclo[3.1.0]hex-2-ene-6-cWo-methanal to 2-oxabicyclo[3.2.l]octa-3,6-diene, is approximately 7 333. Nevertheless this reaction was used in the preparation of a key intermediate in a prostacyclin synthesis34. 

The most popular Cope substrates of this class, represented by (127), can be considered relatives of 1,2-divinylcycloalkanes in which an additional carbon-Concerted Cope rearrangement of (127) is permitted as long as the vinyl group is endo, and leads to a fused bicyclic diene (128), necessarily cis. The ring systems most frequently employed have been bicyclo[2.2. Ijheptenes ix = y= 1). leading to hydroindenes, and bicyclo[2.2.2]octenes (j = 2, y = 1), which afford cu-decalin skeletons. Examples of the former are shown in equation (88) and the latter is illustrated in Scheme 5 (52 - 53). 

Still larger rings may be constructed by this general strategy equation (96) shows the formation of i bicyclo[5.4.0]undecane by oxy-Cope rearrangement of a vinylbicyclo[3.2.2]nonane. ... 

Although the possibility of antara-antara Cope rearrangements has been recognized and suggested as mechanistic alternatives for thermal reairangements of bicyclo[3.2.0]heptadienes, they appear unlikely in die latter case and have been ruled out for simple Cope leairangements. ... 

The Cope rearrangement of 6-endo-vinylbicyclo[3.1.0]hex-2-ene (114) to bicyclo[3.2.1]octa-2,6-diene (115)2 has been shown to take place with a half-life of approximately 1 d at 25 C ( , = 22.9 kcal... 

The readily available aldehyde (118) has served as a suitable precursor for a number of 6-endo-( al-kenyl)bicyclo[3.1,0]hex-2-enes. For example, treatment of (118) with PhsP —CHC02Me gives a mixture of die bicyclic diene esters (121)-(123) (Scheme 18). In view of the stereospecific nature of the Cope rearrangement process (vide supra), it is highly likely that (121) and (122) are derived by bond reorganization of the initially formed Wittig products (119) and (120), respectively. The ratio of (121) (122) is, therefore, a reflection of the (expected) fact that the Wittig reaction produces primarily the rrans-a,P-un-saturated ester (119). The diene ester (123) is, presumably, formed by partial isomerization of (121) and (or) (122). 

On the basis of the work summarized above, it would appear that the Cope rearrangement of 6-(l-alke-nyl)bicyclo[3.1.0]hex-2-enes should be usefully applicable to the synthesis of natural products that possess, as part of their structures, the bicyclo[3.2.1]octane carbon skeleton. Recent work in this area. 

The key intennediate for the synthesis of ( )-sinulaiene (159), a structurally unusual marine natural product, was the bicyclic divinylcyclopropane (160). Successful Cope rearrangement of this substance would be expected to proceed via the endo isomer (161) to produce the bicyclo[3.2.1]octa-2,6-diene (162), possessing the correct stereochemistry at C-4 (exo-isopropyl group) and fimctionality (exo-vinyl group at C-8, enol ether associated with C-6 and C-7) that would allow the straightforward preparation of the tricyclic ring system of ( )-(159). 

Although small in number, the investigations summarized above show that the Cope rearrangement of 7-(l-alkenyl)bicyclo[4.1.0]hept-2-enes is an effective method for the synthesis of usefully functionalized bicyclo[3.2.2]nona-2,6-dienes. 

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