Silyl ketene acetals Ireland-Claisen rearrangement

Also in 1993, Hauske and JuUn reported a similar Ireland-Claisen rearrangement of an acyclic C6 carbamate (Scheme 4.35) [39]. The authors examined three different silyl ketene acetals in the rearrangement, although no experimental details were provided. AU three examples apparently proceeded with complete facial selectivity with respect to the allyUc alkene to afford the syn stereochemistry between the aUyl group and the NHBoc group in the conformation shown. The same rationale for facial selectivity can be applied as for Mulzer s results in the previous scheme. The reason for the low C2,C3 synjanti diastereoselectivity in the propionate example was not addressed. A lack of control of enolate geometry or post-rearrangement epimerization are both possible. 

The Ireland-Claisen reaction of ( )-vinylsilanes has been applied to the stereoselective synthesis of syn- and c/nti-2-substituted 3-silyl alkcnoic acids. a R-2-Alkyl-3-silyl acids are prepared by rearrangement of ( )-silyl ketene acetals which are generated in situ from the kinetically formed (Z)-enolate of the corresponding propionate ester40. Chelation directs the stereochemistry of enolization of heteroelement-substituted acetates in such a way that the syn-diastereomers are invariably formed on rearrangement403. 

Ireland-Claisen rearrangement of silyl ketene acetals (31)... 

Entries 10 to 15 involve use of the Ireland-Claisen rearrangement in multistep syntheses. An interesting feature of Entry 11 is the presence of an unprotected ketone. The reaction was done by adding LDA to the ester, which was premixed with TMS-C1 and Et3N. The reaction generates the T-silyl ketene acetal, which rearranges through a chair TS. 

Ireland-Claisen (silyl ketene acetal) rearrangement... 

As shown earlier (Figure 13.22), silyl ketene acetals can be prepared at -78 °C by the reaction of ester enolates with chlorosilanes. O-Allyl-O-silyl ketene acetals (A in Figure 14.48) are formed in this reaction if one employs allyl esters. Silyl ketene acetals of type A undergo [3,3]-rearrangements rapidly upon warming to room temperature. This variation of the Claisen rearrangement is referred to as the Ireland-Claisen rearrangement. 

Figure 14.51 shows four Ireland-Claisen rearrangements that exhibit simple diastereose-lectivity (see Section 11.1.3 for a definition of the term). The substrates are two cis, trans-iso-meric propionic acid esters. The propionic acid esters in Figure 14.51 are derived from achiral allyl alcohols. This is different from the situation in Figure 14.50. However, these esters contain a stereogenic C=C double bond. Both the esters in Figure 14.51 can be converted into their 7 "-enolates with LDA inpureTHF (cf. Figure 13.16). Silylation affords the two T -con-figured O-allyl-O-silyl ketene acetals A and D, respectively. Alternatively, the two esters of Figure 14.51 can be converted into their Z -enolates with LDA in a mixture of THF and DMPU (cf. Figure 13.17). Treatment with rert-BuMe,SiCl then leads to the Z-isomers B and C of the O-allyl-O-silyl ketene acetals A and D, respectively.

Fig. 11.43. Claisen-Ireland rearrangement of two O-allyl-O-silyl ketene acetals. 7ran.v-sclective synthesis of disubstituted and E-selective synthesis of trisubstituted alkenes.

This method was further improved when it was found that readily available allyl esters of the general formula 493 could also be involved in Claisen rearrangements via intermediate formation of ketene derivatives such as lithium enolates 494 or trimethylsilyl ketene acetals 495 (the Ireland-Claisen variant" ). Moreover, rearrangement of these substrates into unsaturated acids 496 occurred easily at room temperature or below. This was in striking contrast to all previous versions of the Claisen rearrangement, which required heating at elevated temperatures (140-160 °C). The Ireland (silyl ketene acetal) variant of... 

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-... 

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. 

The Ireland modification utilizes silyl ketene acetals derived from allyl ester eno-lates and provides a general method to effect stereocontrolled Claisen rearrangements under mild conditions, making it possible to apply the reaction to acid-sensitive and thermally labile substrates. Moreover, by proper choice of the reaction conditions, one can control the geometry of the enol ethers and hence the stereochemistry of the new C-C bond that is produced in the rearrangement step." ... 

Ireland, R. E., Wipf, P., Armstrong, J. D., III. Stereochemical control in the ester enolate Claisen rearrangement. 1. Stereoselectivity in silyl ketene acetal formation. J. Org. Chem. 1991, 56, 650-657. 

The Ireland contribution to nonactic acid synthesis, outlined in Scheme 4.32, involves a selective silyl ketene acetal formation and Claisen rearrangement in the key step. D-Mannose (209) was readily converted in a straightforward manner to dihydrofuran 212 via 210 and 211 in 36% overall yield. Esterification of the free alcohol with propionyl chloride followed by the an enolate Claisen rearrangement afforded a mixture (89 11) of tetrahydrofuryl propionates 213 after catalytic reduction. 

The Ireland variation is, without doubt, the most important method among the variants of the Claisen rearrangement. The modification consists of the rearrangement of an allyl ester in the form of an ester enolate or silyl ketene acetal to give a y.d-unsaturated acid40 41-80,87 88. 

The AG Claisen can be lowered by use of the Ireland variation, as demonstrated by the rearrangement of silyl ketene acetals 221171. In this case, (A , )-l,6-cyclodecadienes can be obtained. However, the result strongly depends on substituent effects. Thus, the Cope-Claisen rearrangement is only successful with substrate 22 c (X = TBDMS), which upon heating to 214 C in 1,2,4-trichlorobenzene in the presence of 10 equivalents of O.A -bis(trimethylsi-lyl)acetamide for two hours followed by treatment with potassium fluoride monohydrate in hexamethylphosphoric triamide and extraction with 1 N potassium hydroxide gives a 9 1... 

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