Claisen rearrangement ester enolate procedure

It is possible to treat ketones with allyl alcohol and an acid catalyst to give y,5-unsaturated ketones directly, presumably by initial formation of the vinylic ethers, and then Claisen rearrangement.In an analogous procedure, the enolates (126) of allylic esters [formed by treatment of the esters with lithium isopropylcyclohex-... 

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... 

Two groups have reported on the use of the Claisen rearrangement to obtain 2,3-unsaturated C-glycosides. Fraser-Reid and colleagues found the standard reaction applied to derivatives of the allylic alcohol (77) inefficient because of the poor yields of the derived vinyl ethers or because allylic esters e.g. (78) predominated. They were successful, however, in obtaining compounds (79) and (80) by modified procedures (Scheme 5). An alternative synthesis of saturated, and hence unsaturated, C-glycosides was developed as illustrated in Scheme 6. In parallel work Ireland and co-workers used the enol silyl ether approach as shown in Scheme 7 and employed the products in polyether antibiotic syntheses. ... 

General Procedure for Ester-Enolate Claisen Rearrangements ... 

In a program aimed at the total synthesis of polyether antibiotic monensin, Ireland et al. devised a procedure for the in situ silylation of an ester enolate with a j5-leaving group, first executed with the model substrate 165 (Scheme 32). When added to a premixed solution of LDA and TMSCl in 10% HMPA/THF at -100°C, crotyl ester 165 produced after rearrangement at room temperature, desilylation, and treatment with diazomethane, the diastereomeric Claisen products 166 a and 166 b in almost 80% combined yield [63]. The success of this three-component competition experiment depended on the relative rates of N-silylation vs. enolization and -elimination vs. 0-silylation, respectively, with all of these processes occurring on a subminute time scale at -100 C. 

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