Acid-Induced Skeletal Rearrangements

The oxygen bridge in oxabicyclic compounds is an electron pair donor that can stabilize a-carbocations. This characteristic renders oxabicyclic substrates more susceptible to carbocationic skeletal rearrangements resulting in the cleavage of the carbon framework. One such reaction was exploited by Sammes for the synthesis of ( )-cryptofauronol, in which treatment of 145 with Lewis acid induces rearrangement to a decalin ring system, Eq. 100 [57]. 

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A completely different reaction takes place if Si2me6 is reacted with meONa in presence of hexamethylphosphoric acid triamide498 (see p. 21). Trisilane thiols readly undergo a radical-induced skeletal rearrangement ... 

When used for the dehydration of alcohols most acidic oxides result in the formation of alkenes with Saytzeff orientation, i.e. an E2 mechanism is operative. This means that secondary 2-alkanols are transformed to 2-alkenes. A characteristic catalyst achieving such selectivity is alumina treated with alkali metal cations, ammonia, or organic bases [2], Such treatment is necessary because pure, strongly acidic alumina induces skeletal rearrangements and double bond migration. The importance of choosing a catalyst with the appropriate characteristics is illustrated in Scheme 2 [17,18]. 

The last synthesis to evolve which is due to Ito and his coworkers is interesting in that it relies on a stereospecific skeletal rearrangement of a bicyclo[2.2.2]octane system which in turn was prepared by Diels-Alder methodology (Scheme XLVIII) Heating of a toluene solution of cyclopentene 1,2-dicarboxylic anhydride and 4-methylcyclohexa-l,4-dienyl methyl ether in the presence of a catalytic quantity of p-toluenesulfonic acid afforded 589. Demethylation was followed by reduction and cyclization to sulfide 590. Desulfurization set the stage for peracid oxidation and arrival at 591. Chromatography of this intermediate on alumina induced isomerization to keto alcohol 592. Jones oxidation afforded diketone 593 which had earlier been transformed into gymnomitrol. 

Bicyclic 3a//-cyclopentene[8 annulcnc-l,4-(5//,9a//)-dioncs undergo three types of acid-induced transannular reactions (1) Michael addition (5-exo-trig or 6-exo-trig) leading to the tetracyclic diones, (2) 3 + 2-cycloaddition followed by a novel sequential skeletal rearrangement to 2-naphthalenone derivatives, (3) ipso-Friedel-Crafts alkylation accompanied by the rearomatization and the loss of water (Scheme 25). The factors that control the reaction mode of these transannular cyclizations are discussed... 

The silver(I)-mediated electrocyclic ring opening of halocyclopropanes has been used to induce extensive skeletal rearrangements in gcm-dibromospiropentanes, providing rapid construction of naphthalenes and/or indenes (Scheme4.21 ).34 A variety of Lewis acids, Brpnsted acids, and solvent effects were carefully examined before optimal conditions were identified. It was found that subjection of spirocycle 60 to silver acetate in trifluoroacetic acid afforded rearrangement products 61 and 62 in moderate to good yields. The proposed mechanism of the reaction is illustrated in Scheme 4.21. 

A different skeletal rearrangement reaction of norbornadiene takes place on cobalt (Scheme 7.7) [9]. Protonation of the (norbornadiene)cobalt complex 19 induced C-C bond cleavage of the norbornenyl ring to form the cationic aUyl-cobalt complex 20. Reduction with LiBHEtj formed the neutral diene complex 21, which undergoes further C-C bond cleavage upon treatment with acid to give the T -pentadienyl complex 22. 

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