Rearrangements, anionic oxy-Cope

Mullins, R. J. McCracken, K. W. Cope and Related Rearrangements. In Name Reactions for Homologations-Part IT, Li, J. J., Corey, E. J., Eds. Wiley Sons Hoboken, NJ, 2009, pp 88-135. (Review). 

Houk and others performed a computational study with density functional and ab initio calculations to better understand the reaction mechanism of the 

In the total synthesis of (—)-salsolene oxide (17), an architecturally unusual sesquiterpene with an unsaturated bicyclo[5.3.1]undecane core and trisubstituted 

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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... 

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...

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. 

Anionic oxy-Cope rearrangement was also employed for the enantioselective total synthesis of compounds related to marine metabolites (equation 230)305 307, as well as for the preparation of diterpenoide vinigrol (equation 231)308 and cerorubenic acid-in... 

The Cope, oxy-Cope, and anionic oxy-Cope rearrangements belong to the category of [3,3J-sigmatropic rearrangements. Since it is a concerted process, the arrow pushing here is only illustrative. Cf. Claisen rearrangement. 

C Anionic oxy-Cope rearrangement 4d Claisen rearrangement of allyl vinyl ethers... 

Configurational assignment of the aldehyde 2, obtained from l-(2,6,6-trimethylcyclohexenyl)-3-buten-2-ol (1) by an anionic oxy-Cope rearrangement (see p 422), rests on conversion to (+)-dihydromayurone (4, see also p 452)143. 

Methanol-0-4 methyl nitrite, and dimethyl disulfide have been examined as potential chemical probes for distinguishing between alkoxides and enolates in the gas phase.171 Methanol-0-d proved to be unsuitable and methyl nitrite reacts too slowly in contrast, the reactive ambident behaviour of dimethyl disulfide results in elimination across the C—S bond on reaction with alkoxides ( hard bases ) and attack at sulfur by enolates ( soft bases ). This probe has been applied to investigation of the anionic oxy-Cope rearrangement. The dianionic oxy-Cope rearrangement is a key step in a squarate ester cascade involving stereoinduced introduction of two alkenyllithium reagents cis to each other.172... 

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