Silyl ketene acetals alkenes

Lactams can be prepared by [2 + 2] cycloadditions of mines and ketenes50- 52, iniines and ester enolatcs53, imines and silyl ketene acetals, alkenes and isocyanates54 56 and carbodi-imides and ketenes. The stereospecificity of these reactions has been extensively investigated due to the tremendous practical importance of 0-lactam antibiotics57 -59,1I3. 

Fluoride ion can also induce reaction of silyl ketene acetals with electrophilic alkenes. The fluoride source in these reactions is fnT-(dimethylamino)sulfonium diflu-orotrimethylsilicate (TASF). 

Dialkyl(trimethylsilyl)phosphines undergo 1,4-addition to a,/3-unsaturated ketones and esters to give phosphine-substituted silyl enol ethers and silyl ketene acetals, respectively. A three-component coupling reaction of a silylphosphine, activated alkenes, and aldehydes in the presence of a catalytic amount of GsF affords an aldol product (Scheme 76).290 291... 

Silyloxy)alkenes were first reported by Mukaiyama as the requisite latent enolate equivalent to react with aldehydes in the presence of Lewis acid activators. This process is now referred to as the Mukaiyama aldol reaction (Scheme 3-12). In the presence of Lewis acid, anti-aldol condensation products can be obtained in most cases via the reaction of aldehydes and silyl ketene acetals generated from propionates under kinetic control. 

The photo-SNl reaction with particular classes of alkenes - namely enamines, silyl enol ethers and silyl ketene acetals - affords a smooth synthesis of a-aryl ketones,... 

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.

Paternd-Biichi reactions [152] this competition has been investigated for electron-rich alkene substrates for several combinations of carbonyl compounds and electron-donors, e.g. a-diketones and ketene acetals [153], aromatic aldehydes and silyl ketene acetals, and enol ethers. In polar solvents, the assumption of a 1,4-zwitterion as decisive intermediate is reasonable. This situation then resembles the sequence observed for ET-induced thermal [2 -I- 2]-cycloaddition reactions [154]. Both regio- and diastereoselectivity are influenced by this mechanistic scenario. The regioselectivity is now a consequence of maximum charge stabilization and no longer a consequence of the primary interaction between excited carbonyl compound and alkene. Whereas 3-alkoxyoxetanes are preferentially formed from triplet excited aldehydes and enolethers, 2-alkoxyoxetanes result from the reaction of triplet excited ketones or aldehydes and highly electron-rich ketene silylacetals (Scheme 40) [155]. 

Wilcox and Babston later studied the effect of alkyl substitution at C5 for the silyl ketene acetals derived from acetate and propionate esters (Scheme 4.8) [7]. They noted a decrease in rate of the 5-methyl substituted silyl ketene acetals relative to the parent alkene. They also observed a general increase in the rate of rear-... 

A key aspect of stereoselectivity in the Ireland-Claisen rearrangement is the preferential formation of syn (erythro) or anti (threo) pentenoic acids from appropriately substituted allyl silyl ketene acetals. The stereochemical outcome of the reaction is determined by two features (1) the geometry of the silyl ketene acetal and aUyUc alkene, and (2) whether the rearrangement proceeds via a chair-like or boat-Uke transition state. 

In 1984 Fujisawa et al. observed a directing effect due to a CT oxygen stereocenter (Scheme 4.29) [32]. Tandem deprotonation and silylation of the j8-hydroxy allylic ester presumably gave the intermediate sUyloxy silyl ketene acetal. The Z-config-uration of the silyl ketene acetal was a consequence of chelation of the intermediate dianion by the Id cation. The authors postulated that the allylic alkene prefer-... 

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. 

Fleming and Betson found that rearrangement of C6 silyl substituted allyl silyl ketene acetals proceeded with high levels of diastereoselectivity when the allylic alkene was Z configured, but low level when the alkene was E configured (Scheme 4.38) [34]. These results are consistent with the higher aUylic strain... 

Saigo et al. reported a related approach to absolute asymmetric induction by use of an aminoindanol auxiliary (Scheme 4.43) [45]. Treatment of the allyl glycinate with NaHMDS and the unusual silylating agent HSiMejCl gave 92 8 ratio of C2 stereoisomers. The authors proposed that an -silyl ketene acetal was formed and adopted the conformation shown to minimize dipolar interactions. Approach of the allylic alkene from the more sterically accessible face of the oxazolidine would then yield the observed product. The authors did not indicate how the auxiliary would be removed. 

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. 

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. 

In spite of the impressive variety of studies on the Ireland-Claisen rearrangement, several significant Hmitations to the reaction remain. A general solution to the problem of stereocontrolled formation of Cl,Cl-disubstituted silyl ketene acetals has yet to be reported. There is as yet no general catalytic enantioselective variant of the Claisen rearrangement There are as yet no reports of stereoselective generation of acyclic tetrasubstituted alkenes. 

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