Glycolate silyl ketene acetals

In contrast, a-methoxy glycolate silyl ketene acetal 54f enjoys a wider substrate scope. Here, the steric bulk that biases selectivity resides farther from the reactive a-carbon. Despite an initial setback with 54f, excellent results with aliphatic aldehydes could be secured by modulating the size of the ester substituent (entry 4). In fact, with silyl ketene acetal 54h, a broad range of aliphatic aldehydes react with good yield and moderate to excellent selectivities. 

A Special feature of the boron or tin triflate mediated Claisen rearrangement of allylic glycolates or related substrates is that they avoid strongly basic conditions and thus eliminate the need to generate silyl ketene acetal intermediates in which C-silylation is a potential problem497. 

In 1983, Burke et al. reported the enoHzation of an allylic glycolate in the presence of the unprotected cyclopentenone (Scheme 4.45) [48]. Only sHghdy over one equivalent of base was necessary to effect the enolization at -100 °C, indicating that concomitant enohzation of the enone was not competitive. The stereochemical outcome of the rearrangement of the Z-silyl ketene acetal is consistent with the expected chair-like transition state. 

In 1992 Burke et al. reported the selective enolization of a glycolate in the presence of a butenoUde (Scheme 4.47) [50]. The rearrangement of the Z-silyl ketene acetal occurred via a chair-Hke transition state to afford the exo methylene butyro-lactone. The pentenoic add products were transformed into isoavenaciolide and... 

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. 

Kallmerten and Cywin used the glycolate Claisen rearrangement in an approach to zincophorin (Scheme 4.122) [116]. Rearrangement of the Z-silyl ketene acetal of the glycolate ester via a chair transition state afforded the syn stereochemistry in the product The ester was further elaborated to the pyran which constitutes the Cl-Cll subunit of zincophorin. 

Nakai et al. used the glycolate Claisen to elaborate steroid side chains (Scheme 4.123) [117]. The rearrangement of the Z-silyl ketene acetal proceeded via a chair transition state to give the expected C20,C21 (steroid numbering) syn dia-stereomer in high yield. 

Banish et al. used a glycolate Claisen reanangement to establish the C12 and C13 stereocenters and the C14-C15 -alkene in their total synthesis of pseudomo-nic add C (Scheme 4.125) [119]. Because they used the Z-aUylic alkene and Z-silyl ketene acetal, the reananged product possessed the anti configuration. 

Mulzer and Mohr used a glycolate Claisen to establish the C6, C7 stereocenters in an asymmetric synthesis of the asteltoxin Ws-tetrahydrofuran fragment (Scheme 4.127) [121]. Rearrangement occurred via the expected Z-silyl ketene acetal and chair transition state to afford the adjacent carbinol and 4° carbon stereocenters. The high stereoselectivity of the rearrangement using a tetrasubsti-tuted aUyUc alkene is noteworthy. 

Burke et al. employed a cyclic variant of the glycolate Ireland-Claisen rearrangement in the asymmetric synthesis of (-I-)-breynolide (Scheme 4.128) [122]. The rearrangement of the Z-silyl ketene acetal via a boat transition state generated the C3,C4 stereochemistry of the natural product in high yield and stereoselectivity. 

Fujisawa et al. prepared allenic acids with high levels of diastereoselectivity in the rearrangements of silyl ketene acetals derived from propargyl glycolates (Scheme 146) [142]. The authors argue that the stereoselectivity is principally due to a diaxial-hke interaction between the pseudo-axial H and OTMS substituents that is present in the chair-like transition state. 

Table 3 Aldolization with glycolate-derived silyl ketene acetals...

Denmark SE, Chung W-J (2008) Lewis base activation of lewis acids catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes. J Org Chem 73 4582-4595... 

The synthetic utility of this process was enhanced by the development of the glycolate aldol reaction as illustrated in Scheme 7.6. An important feature was that both syn- and anti-1,2-diols could be obtained under identical conditions by appropriately modulating the steric size of the substituents on the silyl ketene acetals [8]. 

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