Claisen rearrangement ketal

Takayanagi, H., Sugiyama, S., and Morinaka, Y., A ketal Claisen rearrangement for a-ketol isoprene unit elongation. Application to a practical synthesis of sarcophytol A intermediate, J. Chem. Soc., Perkin Trans. 1, 751, 1995. 

The Claisen rearrangement of O.S-ketal 49 under neutral conditions (refluxing toluene or xylene) leads to the intermediate 50 which undergoes a rearrangement to the diene ester 52 through enolization and a subsequent 1,5-hydrogen shift within intermediate 51 that carries the hydroxy group at the double bond end (equation 16)30. 

Condensation of the sodium enolate of acetylacetone 194 with carbethoxy-cyclopropyltriphenyl tetrafluoborate 195 led in high yield to acetylcyclopen-tenyl ester 196 and thence to ketal aldehyde 197. The latter with m-methoxy-phenethyl magnesium chloride 198 yielded allylic alcohol 199, which on Claisen rearrangement with dimethylacetamide dimethylacetal afforded amide 200. Conversion to amine, amine oxide, and Cope elimination then led to the desired... 

Ketals are converted to allyl vinyl ethers after Wittig olefination [14]. Wittig reactions permit the incorporation of various substituents into the allyhc terminal of the ether. Enol ethers have been conveniently prepared by cleavage of acetals with various Lewis acids. Cleavage of the ketals with the Lewis acid, for example, triethylsilyl triflate, in the presence of diisopropylethylamine in refluxing 1,2-di-chloroethane afforded the enol ethers (Eq. 3.1.9). The resulting enol ethers were then heated to effect the Claisen rearrangement without isolation. 

An electrochemical oxidative decarboxylation in combination with an ester enolate Claisen rearrangement was reported by Wuts et al. (Scheme 5.2.26) [51]. A variety of allylic esters such as 97 was subjected to an Ireland-Qaisen rearrangement, and the resulting acids (98) obtained were submitted to electrolytic decarboxylation in a divided cell to afford ketals 99. The use of the divided cell was necessary to suppress side reactions such as alkene reduction. 

The Claisen rearrangement of vinyl allyl ethers is a powerful reaction for the preparation of yS-unsaturated carbonyl compounds. The regioselectivity of the ketal version of this reaction has been studied, the results aiding the understanding and prediction of products formed from ketals of unsymmetrical ketones [equation (34)]. The allyl vinyl ether may also be formed by proto-... 

Model studies have demonstrated that the approach of Mariano and his coworkers does indeed permit rapid construction of the pentacyclic yohimbine skeleton (Scheme 129) (41, 42). For example, Diels-Alder reaction of dihydropyridine 193 with methyl vinyl ketone (194) afforded isoquinuclidene 195 which was sequentially ketalized, the nitrogen deprotected, and trypto-phylated to yield the model substrate 196. Treatment of 196 with t-butyl propiolate effected the crucial zwitterionic amino-Claisen rearrangement to efficiently provide the hexahydroisoquinoline 197 having the crucial cis-DE-ring fusion in place. Treatment of 197 under the Wenkert cyclization condi-... 

Claisen-Eschenmoser rearrangement of 7-hydroxyneopine dimethyl ketal (122), on treatment with MV-dimethylacetamide dimethyl ketal in xylene at... 

In summary, a stereoselective 10-step total synthetic route to the antimalarial sesquiterpene (+)-artemisinin (1) was developed. Crucial elements of the approach included diastereoselective trimethylsilylanion addition to a,p-unsaturated aldehyde 16, and a tandem Claisen ester-enolate rearrangement-dianion alkylation to afford the diastereomerically pure erythro acid 41. Finally, acid 41 was converted in a one-pot procedure involving sequential treatment with ozone followed by wet acidic silica gel to effect a complex process of dioxetane formation, ketal deprotection, and multiple cyclization to the natural product (+)-artemisinin (1). The route was designed for the late incorporation of a carbon-14 label and the production of a variety of analogues for structure-activity-relationship (SAR) studies. We were successful in preparing two millimoles of l4C-l73 which was used for conversion to I4C-arteether for metabolism75 and mode of action studies.76,77... 

Claisen-Type Rearrangement of a Mixed Ketal Intermediate... 

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