Stereochemistry of the Cope rearrangement

The stereochemistry of the Cope rearrangement has aroused considerable interest. Doering and Roth set out to determine whether a boatlike (83) or chairlike (84) transition state is preferred. Their experiment, the results of which... 

Stereochemistry of the Cope Rearrangement Boat versus Chair Transition State... 

Interest in the mechanism and stereochemistry of the Cope rearrangement, which attracted considerable attention twenty-odd years ago [13], has recently been rekindled after several years of comparative neglect, and is presently the subject of a considerable amount of critical discussion, with particular emphasis on the synchronicity of the bond-breaking and bond-forming processes [17]. 

The mechanism and stereochemistry of the ortho ester Claisen rearrangement are analogous to those of the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike transition state.158 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike transition state.159... 

The tandem Cope-Cltdsen rearrangement of triene (96 equation 14) creates a product with three new stereogenic centers. Only two of the four possible stereoisomers are formed, namely, aldehydes (100) and (98) in a 78 22 ratio. The factors that control the stereochemistry are the chair-like versus boat-like transition state of the Cope rearrangement (96 giving 97) and the formation of the carbon-carbon bond in... 

Recent studies on the Cope rearrangement of certain germacrane sesquiterpenoids have disclosed some interesting results on the reversibility and conformational control of stereochemistry in this reaction. Jain et al have demonstrated reversibility in three similar systems associated with costunolide and its derivatives [242, R = CH, a-Me, and CH2N(Me)2]. On the other hand, Takeda et 6,180 Qjjjy observed the reversibility of the Cope rearrangement but... 

Highly enantioselective synthesis of cycloheptadienes is obtained when Rh2(S-DOSP)4 is used as the catalyst (Table 5). Examples of the control possible in this chemistry is seen in the reactions with cis-and rranj-piperylenes. Rh2(5-DOSP)4 catalyzed decomposition of the vinyldiazoacetate 14 in the presence of tranj-piperylene results in the formation of the cis-cycloheptadiene 31 in 98% ee, whereas reaction with cw-piperylene results in the formation of the tranj-cycloheptadi-ene 32 in 95% ee (Scheme 12). In both of these reactions, there is full control of relative stereochemistry due to the stereochemical demands of the Cope rearrangement, and the regiochemistry results from preferential cyclopropanation of the least substituted double bond. 

Upon heating the meso version of 3,4-dimethyl-l,5-hexadiene, three products with differing alkene stereochemistry from the Cope rearrangement are possible, but only two are found, with one being highly preferred. Show all three possible products and predict the preference in the distribution. 

The kinetics of the Cope rearrangement have been measured using 1,1-dideuteriohexa-1,5-diene and the possibility of a boat transition state in the Cope rearrangement of hexa-1,5-diene has bwn examined. Trifluoromethanesulphonates (triflates) have been used to study the stereochemistry of solvolytic displacement at unsaturated (vinyl sp ) carbon. Solvolysis of the (Z)- and ( -triflates (611) and (612) in trifluorethanol gives rise to dissimilar ratios of products (613) and (614) a greater proportion of (613) is formed from (611) than from (612). The resultsarebestaccommodated... 

Now the stereochemistry. Assume the thermodynamically more stable iminium ion forms (Me groups cis). The Cope rearrangement occurs from a chair conformation. This puts the Ph, H2, and HI 1 all pointing up both before and after the rearrangement. Assuming the Mannich reaction occurs without a change in conformation (a reasonable assumption, considering the proximity of the nucleophilic and electrophilic centers), the Ph, H2, and HI 1 should all be cis in the product. 

The cytotoxic sesquiterpenoid (-)-quadrone, isolated from the fungus Aspergillus terreus, possesses the constitution and absolute stereochemistry shown in (218). The tricyclic carbon skeleton of this interesting natural product is the same as that found in compound (198), which, as described above (Scheme 28), is readily prepared by thermolysis of the tricyclic diene (197). Thus, it appeared that the Cope rearrangement of a suitably substituted and functionalized derivative of (197) might serve effectively as a key intermediate in a total synthesis of ( )-quadione (218) that is, successful Cope rearrangement of a substrate, such as (219), would provide, stereoselectively, the tricyclic substance (220). Presumably, the intermediate (220) could then be converted into the keto aldehyde (221), which had already been transformed into ( )-quadrone (218). ... 

It is remaikable that the ( )/(Z)-stereochemistry of the oxy-Cope product is not dependent on the erythrolthreo ratio of the 2,3-Wittig rearrangement but on the specific rearrangement procedures used thermal rearrangement exhibits higher ( )-selectivity (92-95%) than the anionic oxy-Cope and siloxy-Cope variants. 

Problem 4.19. A mechanism involving a [3,3] sigmatropic rearrangement (an aza-Cope rearrangement) followed by a Mannich reaction can be drawn for the following reaction. Draw the mechanism. Then predict the stereochemistry of the product obtained when the aza-Cope rearrangement proceeds through a chair conformation. 

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