1.4- Cycloheptadiene, Cope rearrangement

Formation of Seven-Membered Rings The Divinylcyclopropane to Cycloheptadiene (Cope) Rearrangement... 

When ring strain is relieved, Cope rearrangements can occur at much lower temperatures and with complete conversion to ring-opened products. A striking example is the conversion of ris-di vinyl cyclopropane to 1,4-cycloheptadiene, a reaction that occurs readily below -40° C.206... 

An interesting application of a 1,2-disubstituted cyclopropanol in a seven-membered ring-annelation methodology has been developed by Cha et al. [82], The cyclopropanol 124, obtained from methyl 1-cyclopentenecarboxylate (123) and 4-(triisopropylsilyloxy)-butylmagnesium chloride, was converted to a 1,2-dialkenylcyclopropanol bis-silyl ether, which, by a subsequent facile Cope rearrangement, afforded the cycloheptadiene-anne-lated cyclopentane derivative 125 in 32% overall yield (Scheme 11.32). 

In particular the synthetic approach to dihydrofurans (first equation in Figure 4.23) represents a useful alternative to other syntheses of these valuable intermediates, and has been used for the preparation of substituted pyrroles [1417], aflatoxin derivatives [1418], and other natural products [1419]. The reaction of vinylcarbene complexes with dienes can lead to the formation of cycloheptadienes by a formal [3 + 4] cycloaddition [1367] (Entries 9-12, Table 4.25). High asymmetric induction (up to 98% ee [1420]) can be attained using enantiomerically pure rhodium(II) carboxylates as catalysts. This observation suggests the reaction to proceed via divinylcyclopropanes, which undergo (concerted) Cope rearrangement to yield cycloheptadienes. 

Rhodium(II) (iV-dodecylbenzenesulfonyl)prolinate has been found to act as an effective catalyst for the enantioselective decomposition of vinyldiazoacetates to c -divinylcyclopropanes. Combination of this process with a subsequent Cope rearrangement has resulted in a highly enantioselective synthesis of a variety of cycloheptadienes containing multiple stereogenic centres (see Scheme 40). The tandem... 

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-... 

The Cope rearrangement of c/j-di vinylcyclopropanes is thermally allowed and offers an attractive stereoselective approach to cycloheptadienes. Cyclopropanation reactions can be used to prepare divi-nylcyclopropanes, as shown in Scheme 23.120 Reaction of ethyl diazopyruvate with butadiene generated... 

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. 

The intramolecular reaction of the carbene from diazo ester 280, which contains a 1,3-diene moiety in the ester group and a double bond adjacent to the carbene center, leads to the formation of a substituted 1,2-divinyl-cyclopropane, whose CIS isomer then undergoes a Cope rearrangement to give substituted cycloheptadiene. In such a way, bicyclic 281 and tricyclic 282 y-lactones with a neighboring seven-membered carbocycle have been obtained (89JOC930). 

A detailed description of the numerous examples of vinylcyclopropropanes used in transition metal mediated organic synthesis is far beyond the scope of this section and can be found in several reviews. Prominent examples are conversions to open-chain products, as well as formation of four-, five-, six- and seven-membered rings via ring expansion or incorporation of other substrates such as carbon monoxide, alkenes or alkynes. Thus divinylcyclopropanes, obtainable via transition metal catalyzed cyclopropanation reactions, undergo a facile thermal Cope rearrangement to form cycloheptadienes. ... 

Davies and co-workers [12, 35] have exploited one particular aspect of the asymmetric cyclopropanation of alkenes with vinyl diazoacetates, namely, application to substrates suitable for subsequent Cope rearrangement. Cyclopropanation of dienes with predominant cfs-1,2-divinyl diastereoselection makes possible subsequent facile [3,3]-sigmatropic rearrangement with entry to 1,4-cycloheptadienes or bicyclic dienes. Two such examples employing cyclopenta-diene and penta-l,3-diene as substrates and the rhodium(II) prolinate catalyst, Rh2(2S-TBSP)4 in Fig. 1, are shown in Eq. (6) and Eq. (7),respectively cfs-l,2-di-vinylcyclopropanes are presumed to be intermediates in these annulation reactions. In contrast, ethyl diazoacetate and styrene with the prolinate catalyst (Fig. 

Carbene addition to dienes, employing alkenyl-substituted diazoacetates (vide supra), has also been performed in an intramolecular fashion28,29. After in situ Cope rearrangement, bicyclic and tricyclic fused cycloheptadiene derivatives are generated as single diastereomers. 

Nevertheless, ozonolysis of the alkenyl substituents destroys some of the preparative potential of the primary products as vinylcy-clopropanes they would be interesting for many other reactions, for example, for 1,3-and 3,3-sigmatropic rearrangements. [11] It can be inferred from the footnotes of the report [10] that a Cope rearrangement of the primary product 8, derived from the hexadie-noic acid ester 7 and 1, does actually take place at room temperature with the formation of two isomeric cycloheptadiene derivatives. 

H shift in the biosynthesis of vitamin D3. Recently Boland et al. reported, that the ectocarpenes 19 and related substances, which were isolated from the brown algae Ectocarpus siliculosus, are not the sexual pheromones of the algae, but that these cycloheptadienes 19 are formed from the actual pheromones, namely the thermolabile cis-divinylcyclopropanes 18, by a spontaneous Cope rearrangement (Scheme 5) [9]. Thus the Cope rearrangement of 18 resembles a deactivation pathway of the pheromones. 

By a process of cyclopropane formation followed by a Cope rearrangement, rhodium(II)-catalysed decomposition of vinyldiazomethanes in the presence of dienes has been used to generate 1,4-cycloheptadienes. ... 

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