Cope rearrangement transform

The first report on the Pd(II)-promoted Cope rearrangement is the conversion of fw./ra/w-l,5-cyclodecadiene (44) into c/5-l,2-divinylcyclohexane-PdCl2 complex (45) with a stoichiometric amount of PdCl2(PhCN)2 at room temperature. The complex formation is the driving force of this unusual rearrangement [38,39]. A similar transformation of germacrane (l,5-dimethyl-8-isopropyli-dene-/rfflu,/ra j-l,5-cyclodecadiene) takes place[40j. 

Based on the successful series of transformations summarized in Scheme 1, Schreiber and Santini developed an efficient and elegant synthesis of periplanone B (1),8 the potent sex pheromone of the American cockroach, Periplaneta americana. This work constitutes the second total synthesis of periplanone B, and it was reported approximately five years after the landmark periplanone B synthesis by W.C. Still9 (see Chapter 13). As in the first synthesis by Still, Schreiber s approach to periplanone B takes full advantage of the facility with which functionalized 5-cyclodecen-l-one systems can be constructed via anionic oxy-Cope rearrangements of readily available divinylcyclohexanols.5 7 In addition, both syntheses of periplanone B masterfully use the conformational preferences of cyclo-decanoid frameworks to control the stereo- and regiochemical course of reactions carried out on the periphery of such ring systems.10... 

The 1,5 relationship between the olefin and keto groups in 13 satisfies the structural prerequisite for the oxy-Cope transform,11 and, like the first synthesis of periplanone B by Still,9 Schreiber s strategy recognizes that an anionic oxy-Cope rearrangement could provide a powerful and direct method for the assembly of cyclode-cenone 13. On the basis of the model study described previously, it was projected that deprotonation of the free hydroxyl group in 14... 

At 75 C, 2-phenyl-l,3-oxazepine undergoes a [27r + 47t] cycloaddition to 2,5-dimethyl-3,4-diphenylcyclopentadienone to give 3, which at 120 C is transformed into the isomer 4 by a Cope rearrangement.16... 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

The development of synthetic methods for the selective introduction of short-chain perfluoroalkyl groups into organic molecules is of interest in drug development [464]. Fluoromodifications often confer unique properties on a molecule, for example in terms of increased metabolic stability and lipophilicity and, as a consequence, the pharmacokinetic profiles are often improved [465]. Burger and coworkers developed a domino process consisting of a SN reaction combined with a Claisen and a Cope rearrangement which allows the transformation of simple fluorinated compounds into more complex molecules with fluoro atoms [466]. Treatment of furan 2-917 with 2-hydroxymethyl thiophene (2-918) in the presence... 

A domino process based on the twofold addition of alkenyl anions to a squarate ester was used by Paquette and coworkers [96] for the total synthesis of the triqui-nane sesquiterpene hypnophilin (4-284). The three-component reaction of 4-281,4-282 and vinyl lithium gave primarily the trans- and cis-adducts A and B, which furnished D either by an electrocyclic ring opening/ring closure via C or a dianionic oxy-Cope rearrangement (Scheme 4.60). Further transformations led to E and F, which resulted in the formation of 4-283 on treatment with acid. 

Transformation of the 7-oxo-2-enimides 28, available from chiral syn-aldols by a Cope rearrangement, into enantiopure tetrahydropyrans involves reduction of the aldehyde function followed by a fast intramolecular oxa Michael addition. The stereochemical course of the... 

A new multistep synthesis of ( )-reserpine (109) has been published by Wender et al. (258). The key building block of the synthesis is cw-hexahydroiso-quinoline derivative 510, prepared by the extension of the previously elaborated (259) Diels-Alder addition-Cope rearrangement sequence. Further manipulation of 510 gave 2,3-secoreserpinediol derivative 512, which already possesses the required stereochemistry in ring E. Oxidative cyclization of 512 yielded 3-isoreserpinediol (513), which was transformed by the use of simple reaction... 

Another type of diradical intermediate species (27) in Cope rearrangement is formed during thermolysis of optically active frans-4,9-dimethyl-1,2,6,7-cyclodecatetraene 2425 which was studied in order to distinguish between concerted and stepwise mechanisms of Cope rearrangement. The transformation of optically active trans-24 via a concerted mechanism would lead to optically active tetraenes 25 and 26, while the participation... 

Furthermore, the oxy-Cope rearrangement of allenic cycloheptane alcohol 47 (NaOEt, THF, 20 °C, 12 h, 80%) gave rise only to ring-enlarged product 48 without transannular cyclization (equation 15)29. The above transformations can be rationalized either by the fragmentation-recombination mechanism or by a concerted oxy-Cope mechanism29. 

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