Thermal Oxy-Cope rearrangement

Anionic and thermal oxy-Cope rearrangements were reported as steps in the syntheses of various bicyclic systems 586 from divinylcycloalkanes 585 (see Section IV.C.2) (equation 236). The same anionic scheme was applied to prepare ( )-afiricanol and ( )-isoafricanol (hydroazulene systems) as weU as ajmaline-related alkaloids (equation 237). ... 

Due to the short, tethered chain, the thermal oxy-Cope rearrangement of trans- 1,2-divinyl-cyclohexanols ultimately results in the stereocontrolled formation of ( -products (e.g., 7733 or 9928) via chair transition state A /33. 

The thermal oxy-Cope rearrangement of O-protected silyl ether 10 gives a poor yield of 11 (28 %) together with byproduct 12 (32 %), which is formed by trapping 11 via an intramolecular Michael addition. Minor amounts of 13 in the crude reaction mixture result from partial hydrolysis of 12 928. 

The high diastereoselectivily of this triple tandem reaction can be explained by the mechanism depicted in Scheme 3.1.5. At first glance, the thermal oxy-Cope rearrangement of 99 leads to enol 100, which tautomerizes in situ to produce the ketone 101. This ketone can adopt two chair-Uke conformations at the transition state, W and X. A close examination of the transition state Z reveals a psuedo-1,3-diaxial O-allyl-ring methylene interaction. Therefore, this favors the transition state W over X as the reactive conformer to provide the enol 102. Einally, the Claisen rearrangement proceeds anti to the bridgehead alcohol at C5 to afford the desired bicycUc product 103. 

The most frequent rearrangement of substituted hydroxylamines is the thermal [3,3]-sigmatropic rearrangement, the 3-aza-4-oxa-Cope rearrangement also called 3-aza-4-oxy-Cope rearrangement, that proceeds by a cyclic six-membered transition state (equation 1). Albeit the difficulty to prepare hydroxylamine derivatives, this rearrangement proceeds in mild conditions and is useful in the synthesis of several heterocyclic compounds. 

In these cases a modification of the rearrangement, the so-called oxy-Cope rearrangement, is preferred. Thermolysis of a 3-hydroxy-l,5-diene results in the expected 1,5-diene system, but one of the olefinic bonds formed in this process is an enol, which can tautomerize to the corresponding ketone. Thus, a reverse Cope rearrangement cannot take place. Examples are shown in Scheme V/2 [13]. This reaction sequence has been investigated using the thermal behavior of two 1,2-divinylcyclohexanols as model compounds. The trans-iso-... 

The experimental simplicity of the Cope rearrangement is one of its most attractive features. As thermal reactions, the Cope and oxy-Cope rearrangements can be carried out in either of two basic ways. 

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