Decalin, Cope rearrangement

The most popular Cope substrates of this class, represented by (127), can be considered relatives of 1,2-divinylcycloalkanes in which an additional carbon-Concerted Cope rearrangement of (127) is permitted as long as the vinyl group is endo, and leads to a fused bicyclic diene (128), necessarily cis. The ring systems most frequently employed have been bicyclo[2.2. Ijheptenes ix = y= 1). leading to hydroindenes, and bicyclo[2.2.2]octenes (j = 2, y = 1), which afford cu-decalin skeletons. Examples of the former are shown in equation (88) and the latter is illustrated in Scheme 5 (52 - 53). 

Eremopetasidione (440), isolated recently from rhizomes of Petasites japonicus MAXIM, has been used in the treatment of tonsillitis, contusion and poisonous snake bites in Chinese medicine. Recently, racemic 440 was synthesized in 9 steps (30% overall yield) starting from 2-methoxy-4-methylphenol (421) (Scheme 85) . Oxidation of 421 with PhI(OAc)2 in MeOH in the presence of ethyl vinyl ketone (EVK) afforded in 96% yield a Diels-Alder adduct 441, which was converted into sUyl enolate 442 in 96% yield. This enolate further underwent Cope rearrangement to give regio- and stereoselectively the desired c -decalin 443 (70%). Further conversion of 443 to the target molecule 440 was then accomplished. 

The Cope and the oxy-Cope rearrangements are usually carried out either by heating the substrate in a high boiling solvent (e.g., decalin, xylene, diphenyl ether) or vapor-phase rearrangement in a flow apparatus in the case of volatile materials2. Substrates of low molecular... 

Cope substrates derived from bicyclo[2.2.2]oct-5-en-2-ones with an fWo vinyl group undergo Cope rearrangements via boatlike transition state conformations to yield cw-fused decalins, as exemplified by the rearrangement of 1107S. Product 4 is used in the synthesis of lucidu-line 1075,1076, and 6 in the synthesis of reserpine 1077 1078. 

The repetitive Claisen Cope rearrangement can be used as a strategy for the iterative introduction of ( )-isoprene units into a growing chain. Thus, reduction of intermediate aldehyde 44 (see above) to the corresponding alcohol 46 and treatment with acetal 40 affords a 1 1 mixture of the Claisen product 47 and Claisen-Cope product 48 in 30% yield. The tandem Claisen-Cope-Cope product 49 is obtained by heating 48 in decalin to 190°C. 

Similarly the substituted decalin 74 was obtained in good yield by the microwave irradiation of 73. The reaction proceeds via an initial Cope rearrangement to generate the allyl vinyl ether 75 for subsequent [3,3]-sigmatropic transformation to ketone 76. Transannular ene cyclization yielded the product 74. ... 

The Cope rearrangement is prominently featured as a key step in the stereocontrolled four-step synthesis of ci5-decalins advanced by liiao and... 

The related anionic oxy-Cope rearrangement of 126 to 127 was utilized for preparation of the cw-decalin ring system of superstolides A and... 

In 2013, Liao reported the first asymmetric total syntheses of the sesquiterpenoid lactones (+)-eudesmadiene-12,6-olide and (+)-fruUanolide, which were based oti an initial dearomatization of 4-bromo-2-methoxyphenol 240 into the corresprMidmg MOB 241 (Fig. 58) [129]. An asymmetric Diels-Alder reaction wifli the chiral furan R)-2A2 furnished the bicyclo[2.2.2]octenone 243 in good yield with high chemo-, regio-, and stereoselectivities. This compound was further transformed in a few steps to reach (+)-eudesmadiene-12,6-olide, whose m-decalin core was elaborated by a high-yielding anionic oxy-Cope rearrangement of the allylic alcohol 244 (Fig. 58) [129]. 

Luciduline is one of the simpler Lycopodium alkaloids. In an elegant synthesis of this molecule, Scott and Evans constructed the desired tricyclic skeleton from the key decalin ketoamine (D) by an intramolecular Mannich reaction, C-11 being derived from formaldehyde. The c/i-decalin-2,6-dlonesuitable for preparation of (D) was obtained by the oxy-Cope rearrangement of a bicyclo[2-2-2]octene derivative (A) which allowed controlled introduction of the desired sites of asymmetry. 

A computational and experimental study of the oxy-Cope rearrangement of aldol products has been reported (Scheme 22) and a diastereoselective oxy-Cope/ene/Claisen reaction for the synthesis of decalin frameworks possessing four contiguous stereogenic centres has been applied. The aza-Cope/Mannich reaction has been reviewed. ... 

Cope itself. For example, Evans and coworkers exploited the thermal rearrangement of diene 83 for preparation of the cw-decalin system 84, an intermediate in the synthesis of ( )-luciduline, a Lycopodium alkaloid. 

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