Ireland-Claisen rearrangement of silyl ketene acetal

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

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. 

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... 

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. 

Fleming and Betson reported that Ireland-Claisen rearrangement of either the E-or Z-silyl ketene acetals bearing a stereocenter at Cl possessing a TBDPS group gave moderate (R = i-Pr) to excellent (R = Me, Ph) 1,2-asymmetric induction (Scheme 4.32) [34]. The transition states were proposed to adopt a conformation with the CT hydro-... 

Ishizaki et al. found that use of a triisopropylsilyl (TIPS) protecting group gave optimal facial selectivity in the Ireland-Claisen rearrangement of C5 hydroxyalkyl substituted allylic alkene, with the silyl ketene acetal attacking anti to the O-sUyl group (Scheme 4.33) [35]. The rearrangement presumably proceeded via a chair-... 

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 earliest examples of Ireland-Claisen rearrangements of allyl silyl ketene acetals bearing a stereocenter at C6 were reported by Cha and Lewis in 1984 (Scheme 4.36) [40]. In contrast to the nitrogen C6 substituents, oxygen substituents exhibited considerably less facial bias. Rearrangements of the acetate esters of either the Eor Z alkenes gave only 1.3 1 and 1.4 1 C3,C6 anti.syn ratios, respectively. 

Kocienski et al. have used a vinyl silane as a masked vinyl alcohol in the synthesis of the C26 to C32 fragment of rapamycin (Scheme 4.82) [77]. Ireland-Claisen rearrangement of the vinylsilane glycolate ester via the Z-silyl ketene acetal yielded the corresponding anti pentenoic acid with high diastereoselectivity. Oxidative cleavage of the furyl substituent and Tamao oxidation then afforded the allyhc alcohol. 

McIntosh et al. have applied the Ireland-Claisen rearrangement of bis-allyl silyl ketene acetals in studies directed toward the synthesis of the eupomatilones (Scheme 4.135) [128]. The 1,2-transposition of the alkene, which occurred in the rearrangement afforded a reactive vinyl epoxide (cf Scheme 4.83). Stereoselective cyclization of the carboxylic acid onto the vinyl epoxide generated the 5-aryl lactone, which was further manipulated to the putative structure of 5-epi-eupoma-tilone-6. 

Knight et al. have employed a ring contraction via the Ireland-Claisen rearrangement of an aryl lactone to generate a 2,3,4-trisubstituted tetrahydrofuran intermediate in the synthesis of ( )-samin (Scheme 4.143) [138], The rearrangement proceeded via a boat transition state of the cyclic -silyl ketene acetal. 

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. 

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.

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