AUyl acetates rearrangement

In contrast to the acyclic aUyl silyl ketene acetals, cyclic substrates may preferentially rearrange through either the chair or boat transitions states. In 1981 Bartlett and Pizzo reported that treatment of cyclohexenyl propionates under either set of conditions reported by Ireland resulted in the formation of the same major isomer (Scheme 4.17) [20]. They concluded that the -silyl ketene acetal rearranged preferentially via a chair-hke transition state, while the Z-silyl ketene acetal rearranged via a boat-like transition state. These conclusions were recently supported computationally by Houk et al., who reported a 1.0 kcal/mol preference for the boat transition state for the Z-geometry in the analogous OMe ketene acetal and a 1.4 kcal/mol preference for the chair transition state for the -geometry in the OMe ketene acetal [18]. 

An attractive alternative synthesis was likewise developed by Firmenich. [105, 106] Pentylcyclopentenol, is enzymatically transesterified with dimethyl malo-nate, whereby the (S)-enantiomer remains unaltered, but this can be racemised in the presence of sulfuric acid. The malonate is converted into an allylsilylke-tene acetal, which is then subjected to a Claisen rearrangement this proceeds under the control of the aUyl alcohol at relatively low temperatures and with high stereoselectivity. After decarboxylation, there follows the key step in the synthesis a n-selective epoxidation with highly electrophilic peroxy-acids, such as peroxytrifluoroacetic acid. The high n-selectivity arises from electrostatic effects between the more electron-rich r-side of the douple bond and the partial... 

Ireland noted in an early report that the rate of the rearrangement increased significantly with alkyl substitution at Cl, C4 or C6 (Scheme4.7) [1]. This is consistent with extensive computational and experimental studies of the parent aUyl vinyl ether [6], although the corresponding calculations of 2-OR-ketene acetals have not been reported. 

Inanaga et al. reported the first example of a nucleophileotalyzed Ireland-Claisen rearrangement (Scheme 4.11) [12]. Conjugate addition of tricyclohexyl-phosphine to aUyl acrylates generated intermediate phosphonium allyl sUyl ketene acetals, which underwent rearrangement to yield a-substituted acrylates after elimination of the phosphine. 

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. 

This route to ketene N,0-acetals was further investigated by Welch who found that methylation of amides with methyl triflate, followed by addition of lithium aUyl aikoxides afforded allylic ketene N,0-acetals that rearranged at room temperature [14]. Lactams also undergo this reaction (Scheme 7.8) [16]. 

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