Ring synthesis Cope rearrangement

In contrast to the synthesis of carbocyclic rings, the Cope rearrangement has been used sparsely for generating azepinones. Recently, the enantioselectivity of the conversion of 2-aza-divinylcyclopropane 286 has been investigated. The synthesis started from the optically active cyclopropanecarboxylic acid (90% ee), which had been converted into the isocyanate 286 by initial azidation to 285 and a consecutive Curtius rearrangement. Furthermore, the conditions of the iso-... 

When the allene and isolated double bond are both incorporated into a large ring, then Cope rearrangement affords 2,3-divinylcycloalkenes, as seen in equation (30). The cyclic bisallene (83) affords 2,3-di-vinyl-1,3-cyclohexadiene (84), again in excellent yield. These examples illustrate just how useful the allene variation of the Cope rearrangement is in the synthesis of interesting 1,3-dienes. 

Schroder and Witt ° have reported the synthesis of crown ethers having fluctuating ring sizes which they have termed breathing crown ethers . The structures are based on the bullvalene subunit and, as the tetracyclic subunit undergoes Cope rearrangement, the size of the macroring likewise varies. The synthetic steps follow the conventional routes used for the preparation of crown ethers and are illustrated in Eq. (3.44). 

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. 

Scheme 1. Schreiber s oxy-Cope rearrangement/cyclobutene ring opening strategy for the synthesis of cyclodecadienone 8.

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... 

Scheme 79 Snapper s total synthesis of asteriscanolide (116) by sequential intramolecular cyclobutadiene cycloaddition, ring-opening CM (ROCM), and Cope rearrangement [167]...

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. 

The Cope and oxy-Cope rearrangement are very useful in organic synthesis, particularly when the 1,5-diene system is incorporated in a ring, then intringuing cyclic compounds may result. Also, the Cope and oxy-Cope rearrangements are greatly facilitated for a cw-1,2-divinylcyclobutane (Eq. 15)), resulting in the formation... 

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... 

The oxy-Cope rearrangements have found use in the synthesis of medium sized rings as in the following example. 

In the synthesis of ( )-palominol and ( )-dolabellatrienone from famesol, Corey and Kania84 employed a dianion accelerated oxy-Cope rearrangement to form the 11,5-trans-fused ring system of the dolabellanes. Diol 112 was treated with potassium hydride in THF to afford a 1 1 mixture of products with iraws-ll,5-fused ring systems, 113 and... 

As an application of this procedure, Snapper succeeded in the formal total synthesis of (+)-astericanolide. Treatment of iron complex 62, which is prepared from cyclopentenol derivative 60 and iron complex 61, with MeaNO gives fused cyclobutene derivative 63. ROM of cyclobutene of 63 using Ig under ethylene gas smoothly proceeds to produce an eight-membered ring of 64 via Cope rearrangement. The resulting product 64 is converted into Wender s intermediate for the synthesis of (+)-astericanolide ... 

Reaction of vinyl Grignard reagents with a-halo ketones. Vinylmagnesium bromide or vinyllithium (2 equivalents) reacts with a-halocycloalkanones to give 1,2-divinylcycloalkanols, used in oxy-Cope rearrangements for synthesis of large ring ketones (c/ 7, 302-303 8, 412 414).8 Examples ... 

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