Stereoselectivity Cope rearrangement

Several transition metal ions and complexes, especially Pd(II) salts, have been found to catalyze Cope rearrangements.207 The catalyst that has been adopted for synthetic purposes is PdCl2(CH3CN)2, and with it the rearrangement of 14 to 15 and 16 occurs at room temperature, as contrasted to 240° C in its absence.208 The catalyzed reaction shows enhanced stereoselectivity and is consistent with a chairlike TS. 

The stereoselectivity achieved in the synthesis in Scheme 13.12 is the result of a preferred conformation for the base-catalyzed oxy-Cope rearrangement in Step B. Although the intermediate used in Step B was a mixture of stereoisomers, both gave predominantly the desired relative stereochemistry at C(4) and C(7). The stereoselectivity is based on the preferred chair conformation for the TS of the oxy-Cope rearrangement. 

The combined C-H activation/Cope rearrangement generates a new C-H bond in a highly stereoselective manner and, therefore, has the potential to be a strategic reaction in synthesis. An example of this is the enantiose-lective synthesis of (+)-sertraline as shown in Scheme l.91 The C-H insertion step proceeded smoothly to form 17 with 99% ee. The conversion of 17 to (+)-sertraline could be readily achieved using conventional steps. 

Dihydronaphthalenes are remarkable substrates for the combined C-H activation/Cope rearrangement, but under certain circumstances, further cascade reactions can occur. This was seen in the Rh -DOSP -catalyzed reaction of vinyldiazoacetate 26 with dihydronaphthalene 25 (Equation (35)).96 In this case, the isolated product was the formal C-H insertion product. The reaction proceeded through a combined C-H activation/Cope rearrangement to form 27, followed by the reverse Cope rearrangement. As both steps were highly stereoselective, the formal C-H insertion product 28 was produced with very high stereoselectivity (>98% de, 99.6% ee).96... 

Schneider and Rehfeuter68 have reported that enantiomerically pure 1,6-disubstituted-1,5-dienes with an aldol substitution pattern can undergo stereoselective Cope rearrangements in good yield. For example, 1,5-diene 97 underwent Cope rearrangements in toluene in sealed flasks at 180 °C for 2 h to afford, after chromatography, an 89% yield of a 97 3 diastereomeric mixture of 98 and 99, respectively (equation 54). 

TV-Glycosyl homoallylamines have been shown to undergo a stereocontrolled Lewis acid-catalyzed aza-Cope rearrangement to produce chain-extended amino sugars85. The reactions proceed in good to excellent yields with high stereoselectivity. Schiff base... 

A stereoselective convergent synthesis of hydroazulenes 538 was also based on a tandem intermolecular cyclopropanation-Cope rearrangement sequence with predictable stereocontrol (equation 211)262. 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

It has been established that the course of the sequential pericyclic reaction of cyclopentadienones with acyclic conjugated alkadienes depends on the reaction temperature, thermal treatment at low temperatures affording 3a,4,7,7a-tetrahydroinden-l-one derivatives by way of a Cope rearrangement (see Scheme 38). Roman et al have developed an efficient stereoselective synthesis of enantiomerically pure i-nitrotricyclo[5.2.2.0 ]undeca-3,8-dienes via a tandem consecutive asymmetric Diels-Alder-Cope rearrangement (see Scheme 39). Adducts... 

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 is the conversion of a 1,5-hexadiene derivative to an isomeric 1,5-hexadiene by the [3,3] sigmatropic mechanism. The reaction is both stereospecific and stereoselective. It is stereospecific in that a Z or E configurational relationship at either double bond is maintained in the transition state and governs the stereochemical relationship at the newly formed single bond in the product.137 However, the relationship depends upon the conformation of the transition state. When a chair transition state is favored, the EyE- and Z,Z-dienes lead to anli-3,4-diastereomcrs whereas the E,Z and Z,/i-isomcrs give the 3,4-syn product. Transition-state conformation also... 

Oxy-Cope rearrangement (7, 302-303 8, 412-414). Further studies indicate that the rearrangement of 1,5-diene alkoxides can be used for stereoselective generation of asymmetry. An application is the stereoselective synthesis of eryf/iro-juvabione (1), a sesquiterpene from Abies balsamea, shown in equation (I). ... 

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... 

The allyl-transfer reaction based on 2-oxonia Cope rearrangement allows highly stereocontrolled chirality transfer. Triflic acid has been shown to induce the rearrangement of the 251 allyl sterols into 22-homoallylic sterols with high stereoselectivity without side reactions86 [Eq. (5.316)]. The protocol, however, is not effective for syn substrates (for example, 251, R = H, R = COOEt). 

Stereoselective preparation and Cope rearrangement of 2-CF3-substituted r-2,3-bis(alkenyl)oxiranes opens a facile approach to diverse 2-trifluoromethyl-4,5-dihydrooxepines. Subsequent reduction or oxidation of the latter provide 2-CF3-substituted oxepanes or oxepines, respectively <2004CL438>. 

Whether for these reasons or not, the reactivity indices excited little interest among organic chemists, and it was only after Woodward and Hoffmann s early papers that perturbational methods were widely invoked again. Fukui and Fujimoto17-90 adopted Fukui s frontier orbital theory to explain the Woodward-Hoffmann rules, and both they91 and Hoffmann and Woodward92 were able to explain stereoselective effects [such as the preference in the Cope rearrangement (1) (2) for the chair-like intermediate (16) rather than the boat-like one (17), and the tendency for Diels-... 

A short review of the first 100 years of ketene chemistry covers haloketenes, Wolff (g) rearrangements, stereoselective nucleophilic attack, dimerization, cycloadditions, ketene-Claisen and -Cope reactions, bisketenes, and free radical processes.12 ... 

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