Cope rearrangement of divinylcyclopropanes

It is well established that steric effects hinder the Cope rearrangement of divinylcyclopropanes. An interesting example of this steric effect is seen in the reaction of 33 with cis- and trans-l-acetoxy-butadiene (Scheme 13). ° The reaction of 33 with trans-1-acetoxy-l, 3-butadiene leads cleanly to the [3+4] annulation product 34 in 67% yield. In contrast, the product from the reaction of 33 with c/j-l-ace-toxy- 1,3-butadiene is the cw-divinylcyclopropane 35 (80% yield), and high temperatures (220 °C) are required to convert 35 to the [3+4] annulation product 36. The effect of alkene geometry on the stereochemistry and the rate of reaction is readily explained by considering the boat transition state for the Cope rearrangement of divinylcyclo-propanes (structure 37). A trans diene substituent (Y) would generate a trans product (34), whereas a cis substituent (X) would lead to a cis... 

A symmetry approach to the effect of temperature and substitution on Cope rearrangements has revealed that with increasing temperature the loss of symmetry can be considered as a collective variable which has a positive linear relationship with temperature. The results of an aromatic Cope rearrangement of a trans-l-aryl-2-ethenylcyclobutanecarbonitrile have been reported for the construction of the fused benzocyclooctene ring. The effects of gem-dimethyl substitution on the cyclopropane, alkene geometry, relative stereochemistry of the cyclopropane, and steric and electronic effects of functional groups on the thermal Cope rearrangement of divinylcyclopropanes have been reported (Scheme 10). " ... 

Electronically rich 1,3-butadienes such as Danishefsky s diene react with chromium alkenylcarbene complexes affording seven-membered rings in a formal [4S+3C] cycloaddition process [73a, 95a]. It is important to remark on the role played by the metal in this reaction as the analogous tungsten carbene complexes lead to [4S+2C] cycloadducts (see Sect. 2.9.1.1). Formation of the seven-membered ring is explained by an initial cyclopropanation of the most electron-rich double bond of the diene followed by a Cope rearrangement of the formed divinylcyclopropane (Scheme 65). Amino-substituted 1,3-butadienes also react with chromium alkenylcarbene complexes to produce the corre-... 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

Cycloheptadiene (340) is obtained by the Cope rearrangement of cis-divinylcyclopropane (339.) Based on this reaction, highly diastereoselective and enantioselective construction of the 1,4-cycloheptadiene 343 (98% ee) was achieved by domino asymmetric cyclopropanation to generate cA-divinylcyclopropane... 

Not unexpectedly, Irons-1,2-divinylcyclopropane (4) is much more stable than the cis isomer (1) and is a readily isolable compound. Nevertheless, at elevated temperatures, e.g. 190 C, (4) undergoes smooth bond reorganization to provide 1,4-cycloheptadiene (2) in essentially quantitative yield Thus, at the time that the Cope rearrangement of 1,2-divinylcyclopropane systems was discovered, it was already clear that both cis and trans isomers could in principle, serve as suitable substrates for the reaction. As it turns out, this is an important reaction characteristic, since, in most (but not all) cases, it makes uiuiecess-ary the stereoselective preparation of either the cis or trans starting material. 

Table 1 Cope Rearrangement of some cu-l,2-Divinylcyclopropane Systems ...

Although further work in this area is desirable, it appears that in the Cope rearrangement of simple frans-divinylcyclopropanes, such as (33) and (34), enantioselectivity is poor. 

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 the Cope rearrangement of ds-1,2-divinylcyclopropanes to 1,4-cyclohep-tadienes has been known since the early 1960s as a particular case of n ... 

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) . 

Ozkan, I., Zora, M. Transition Structures, Energetics, and Secondary Kinetic Isotope Effects for Cope Rearrangements of cis-1,2-Divinylcyclobutane and cis-1,2-Divinylcyclopropane A DFT Study. J. Org. Chem. 2003, 68, 9635-9642. 

Sperling, D., Reissig, H.-U., Fabian, J. [1,3]-sigmatropic rearrangements of divinylcyclopropane derivatives and hetero analogs in competition with Cope-type rearrangements. A DFT study. Eur. J. Org. Chem. 1999,1107-1114. 

The Cope rearrangement of trans- and, notably, cu-l,2-divinylcyclopropanes 1 to 1,4-cyclohep-tadienes 2 (see Section 2.4.5) is a well-known reaction of importance in synthesis. i 11 , i s s. 159... 

In general, the reaction is not stereoselective and EjZ mixtures of isomers are obtained. Thus, l,l-dichloro-2,3-diethylcyclopropane (11) yielded a 1 1 synjanti mixture of l-ethylidene-2-vinylcyclopropane (12). This example also illustrates the effect of reaction time on the products. Product 12 is obtained in 80-90% yield after 30 minutes at 25 °C. After 2.3 h of reaction time, however, the yield is drastically reduced by isomerization to 1,2-divinylcyclopropane (13) and a subsequent Cope rearrangement of the cw-isomer of 13, followed by isomerization, to cyclohepta-1,3-diene (14). Higher reaction temperatures also lead to rearrangements. ... 

Using this method, 3-(2,2-dimethyl-3-vinylcyclopropyl)cyclohex-2-enone 11 or its 2-methyl derivative were prepared from lithium [c -(and-rra . )-2,2-dimethyl-3-vinylcyclopropyl]-phenylsulfanylcuprate (10) and 3-iodocyclohex-2-enone, or its 2-methyl derivative. Cope rearrangement of the resulting 1,2-divinylcyclopropanes gave bicyclo[5.4.0]undecadienones. ... 

The reactions of ( )- and (/)-/i-silylacryloylsilaries with lithium enolates of u, -unsaturated mefhyl ketones afford cis-5,6- and trflns-5,6-disubstituted 3-cyclohepte-nones, respectively (Scheme 10.227) [590, 591]. The observed stereospecificity in fhe [3-t4] annulation can be rationalized by a reaction mechanism via an anionic oxy-Cope rearrangement of the 1,2-divinylcyclopropane intermediate 161 generated by [2-1-1] annulation between the substrates. 

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