Sigmatropic rearrangements Ireland-Claisen rearrangement

This conclusion has been applied in the Ireland-Claisen rearrangement 5.56 —> 5.58, which is one of the most frequently used [3,3] sigmatropic rearrangements, because it sets up two usefully substituted stereogenic centres with high levels of predictability, stemming from the chair-like transition structure 5.57. 

Danishefsky and coworkers have demonstrated the conversion of lactones to carbocycles by the 3,3-sigmatropic shift of silylketene acetals. Jq the total synthesis of the Fusarium toxin equisetin, for example, keto lactone (138) was converted to its bissilyl derivative (139) by reaction with 2 equiv. of LDA and an excess of TMS-Cl. In situ thermolysis of ketene acetal (1 ) led to a very smooth transformation into ester (140), which was carried on to equisetin (Scheme 26). This methodology was also applied by Schreiber and Smith in the preparation of the cyclohexyl moiety of the immunosuppressive agent FK-506. Ireland-Claisen rearrangement of silylketene acetal (142), prepared by treatment with TBDMS-OTf and triethylamine at low temperature, provided, after hydrolysis of the silyl ester, the carboxylic acid (143) in 71% overall yield (Scheme 27). The strict translation of configuration via a boatlike transition state is typical for this permutation. 

One key element of the total synthesis of (-)-dactylolide (-)- developed by McLeod et al. is a [3,3]-sigmatropic Ireland-Claisen rearrangement which allows the selective formation of the stereogenic centre at C-19. 

Protection of the primary and acylation of the secondary alcohol prepares the way for an Ireland-Claisen rearrangement. The E-enolate is produced and the [3,3] sigmatropic rearrangement transmits the chirality across the alkene to set up two new centres. The mechanism of the Ireland-Claisen rearrangement is described above 94 and occurs suprafacially across the backbone of the molecule through a chair-like transition state. We hope you agree both with the relative stereochemistry of the new centres and the E stereochemistry of the new alkene. 

Neier and coworkers have used a domino Diels-Alder/Ireland-Claisen process for the synthesis of (rac)-juvabione 4-46 and (rac)-epijuvabione [15]. Since neither the Diels-Alder reaction of the acetal 4-44 and methyl acrylate nor the sigmatropic rearrangement seemed to be stereoselective, these authors obtained the cyclohexene derivative 4-45 as a mixture of three diastereomers (Scheme 4.9). 

Sigmatropic rearrangements proceed via closed transition states in the Claisen-Ireland variation a silyl-enol ester, 27 or 28, is used, which may be selectively generated in (Z) or (E) configuration12 (Section A. 1.6.3.1.). As shown in the transition states 32 and 29, this results in the formation of 30/31 and 33/34. 

In 1972, a further brilliant improvement on the Claisen rearrangement was realized by Ireland and co-woikers. Ester enolization wiA lithium dialkylamide bases, followed by silylation with TMS-Cl, generated reactive silyl ketene acetals at -78 °C or lower temperatures. Sigmatropic rearrangement to easily hydrolyzable 7,8-unsaturated silyl esters occurred at ambient tempontures (15 16 17 equa-... 

The ability of charged substituents to accelerate the 3,3-sigmatropic reiarrangement of allyl vinyl ethers (the Claisen rearrangement) has also been documented. The effect of oxyanion substituents on the rate and course of aliphatic Claisen rearrangements has been the subject of particular attention. " In 1972, Ireland and Mueller reported that the lithium enolate derivatives of allyl esters undergo rapid and effi-... 

The interest generated by the Claisen rearrangement prompted the development of a considerable number of different versions of [3,3]-sigmatropic rearrangements. Thus, in 1972 Ireland reported the rearrangement of allyl trimethylsilyl ketene acetals to yield y,6-unsatura-ted carboxylic acids. ... 

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