Cope rearrangement anionic

In this beautiful synthesis of periplanone B, Still demonstrated a classical aspect and use of total synthesis - the unambiguous establishment of the structure of a natural product. More impressively, he demonstrated the usefulness of the anionic oxy-Cope rearrangement in the construction of ten-membered rings and the feasibility of exploiting conformational preferences of these medium-sized rings to direct the stereochemical course of chemical reactions on such templates. 

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... 

C4-insertions by means of a sigmatropic rearrangement process have been described using either a thermal Cope reaction, anionic Claisen amide enolate and zwitterionic aza-Claisen rearrangements. 

An important improvement in the oxy-Cope reaction was made when it was found that the reaction is strongly catalyzed by base.212 When the C(3) hydroxy group is converted to its alkoxide, the reaction is accelerated by a factor of 1010-1017. These base-catalyzed reactions are called anionic oxy-Cope rearrangements, and their rates depend on the degree of cation coordination at the oxy anion. The reactivity trend is K+ > Na+ > Li+. Catalytic amounts of tetra-rc-butylammonium salts lead to accelerated rates in some cases. This presumably results from the dissociation of less reactive ion pair species promoted by the tetra-rc-butylammonium ion.213... 

The stereochemistry of acyclic anionic oxy-Cope rearrangements is consistent with a chair TS having a conformation that favors equatorial placement of both alkyl and oxy substituents and minimizes the number of 1,3-diaxial interactions.214 For the reactions shown below, the double-bond configuration is correctly predicted on the basis of the most stable TS available in the first three reactions. In the fourth reaction, the TSs are of comparable energy and a 2 1 mixture of E- and Z-isomers is formed. 

Scheme 2.193. Domino [2,3]-Wittig/anionic-oxy-Cope rearrangement process...

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]. 

In this domino process, the 1,2-addition is followed by an anion-accelerated oxy-Cope rearrangement and a transannular Dieckmann-type cydization. 

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. 

Radical-anionic Cope rearrangement, 5 Rehybridization effects, in cycloaromatiza-tion reactions, 21-22 Relative selectivity (RS) parameter, 287... 

The Cope rearrangement of alkoxide ions is much faster (1010 - 1017 times) compared with the normal oxy-Cope rearrangement. This is also called anionic oxy-Cope rearrangement and occurs under mild conditions. 

In the total synthesis of cerorubenic acid-III methyl ester (105), diene 102 was converted to enantiopure tricyclic ketone 103 through an anionic oxy-Cope rearrangement (equation 56)82. Conversion of 102 to 103 afforded the entire ABC substructure of 104 and 105, most notably the double bond occupying a bridgehead site. 

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