Silylacetals

Silylation using the silylacetate (3.1.14) [49] involves the initial formation of the acetate carbanion, which abstracts a proton from the carbonyl compound or alcohol (Scheme 3.2, Table 3.5). When the reaction with a ketone is conducted in the presence of an aldehyde, crossed aldol products are obtained (see Chapter 6). 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

Silylacetals of difluoroketene have an important synthetic potential and constitute an alternative to the Reformatsky reagent generated from ethyl bromodifluoroace-tate." They are prepared by reduction by a bromo-, iodo-di-, or trifluoroacetate in the presence of a trialky Isilylchloride. Despite the fact that they are difficult to prepare, they behave similar to their nonfluorinated analogues (aldolization reactions, conjugated addition, etc.) (Figure 2.27)." ... 

The isolation of the sily lacetal ketene is required when the reaction is catalyzed by a chiral Lewis acid. However, due to its instability, isolation yields of the compounds are very low. Reaction of difluoroketene silylacetal with electrophiles affords adducts with excellent ee (Figure 2.28). ° The instability of these difluoroketene silylacetals is due to the facile migration of the silyl group from oxygen to carbon, affording... 

Photocycloaddition of aromatic carbonyl compoimds with p,p-dimethylketene silylacetals gave 2-alkoxy-4-aryloxetanes <98JCS(P1)3253>. A similar photoaddition of derivatives of stilbene to chloranil gave the isomeric spiro oxetanes 16 in very high total yields <99JOC2250>. 

Photocycloaddition reactions of aromatic aldehydes with cyclic ketene silylacetates have been investigated by Abe and coworkers [61]. Regio- and diastereoselective formation of the bicyclic 2-alkoxyoxetanes 69 was observed in high yields. Hydrolysis of these acid-labile cycloadducts with neutral water efficiently gave aldol-type adducts 70 with high threo-selectivity (Sch. 18). 

Michael additions of ketene alkyl silylacetals. In the presence of TiCl, (1 equiv.) these acetals undergo Michael addition to ethyl propiolate via a titanate intermediate. 

Triethylborane induces the radical reaction of ketene silylacetal with polyhalomethanes to yield 3,3-dihaloacrylates (equation 140)945. 

Summary. Intra- and intermolecular carbene or carbenoid reactions resulting from the photochemical and Cu(I)-, Rh(II)-, or Ru(I)-catalyzed decomposition of a-diazo-a-silylacetic esters are described. Among the products reported are (alkoxysilyl)ketenes, silaheterocycles, 1-trialkylsilylcyclopropane-l-carboxylates, and products derived from transient carbonyl ylides. 

Enolates, which are the actual propagating species, exist in the E (11) and Z (12) configurations. The E/Z ratio of the living chain-ends can be indirectly determined by reacting the propagating enolates 11 and 12 with chlorotrimethylsilane and converting them into the corresponding ketene silylacetals 13 and 14, which are characterized by NMR spectroscopy (equations 23 and 24). ... 

Wnek and coworkers synthesized a four-arm star-shaped PMMA with a cyclic siloxane core, as shown in equation 63. Four ketene silylacetal units were first attached to 1,2,3,4-tetramethylcyclotetrasiloxane (78) to obtain the tetrafunctional core 79, which was used as an initiator of the GTP of MMA with formation of the targeted four-armed star-shaped PMMA (80). 

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]. 

The reaction of a silylacetate derivative with an aldehyde or ketone was initially studied by Rathke and Yamamoto. Rathke and coworicers studied the addition of the lithium anion of r-butyl (trimethylsi-lyl)acetate (340) with a variety of aldehydes and ketones (equation 78). The anion can be formed directly from the silyl compound on treatment with LDA. The reaction proceeded to give the conjugated alkenes in excellent yields. Unsaturated compounds reacted via 1,2-addition. No discussion of alkene geometry was present. In the Yamamoto work, the ethyl (trimethylsilyl)acetate derivative (342) was used in a variety of reactions with aldehydes and ketones (equation 79). The anion was formed wiA dicyclohexyl-amide in THF. It was stated in the experimental section that the ( ) (Z) ratios of alkenes were dependent on the reaction conditions. In all the examples presented in this work, the ( )-isomer was predominantly formed. 

Oxazolidine 134 is a masked trifluoroacetaldehyde imine that generates in situ the corresponding imine 135 under Lewis acid catalysis conditions. Lewis acid-catalyzed reactions of 134 with TMS-cyanide and ketene silylacetal provide adducts 136 in high yields with good diastereoselectivities (see Scheme 9.29) [56]. Conventional chemical transformation of 137 produces 3-amino-4,4,4-trifluorobutanoic acid 138. Similarly, tri-fluoroacetone oxazolidine 139 is used for the synthesis of 2-trifluoromethylalanine 142... 

The reactions of aldehydes with enoxysilanes of ketones usually exhibit poor stereoselectivity. Enoxysilanes derived from esters and thiolesters, on the other hand, give good results. Chirality has been introduced either on the Lews acid or by using an ester of an enantiopure alcohol. As in the case of enolate reactions, one or two new stereocenters may be created. All these reactions take place at low temperatures, and they are sometimes limited by the instability of certain ketene silylacetals. 

Chiral boranes have been recommended as Lewis acids catalysts by Reetz [689], Yamamoto [787, 788], Kiyooka [795, 1302], Masamune and their coworicers [796, 797], These groups used, respectively, boranes 2.61, 3.9 (R = H, R = /-Pr), 3.10 (R = i-Pr or tert-Bu, R = H) and derivatives of 3.12 and 3.13. These boranes are very efficient catalysts in asymmetric additions of symmetrically substituted ketene silylacetals 6.113 to aldehydes (Figure 6.94). Similar reactions can also be conducted with enoxysilanes derived from methylketones or from tert-Bu thiolacetate [787, 794, 796], Oxazaborolidine 3.10 derived from tryptophan 3.11 is also a very potent catalyst [794],... 

With the exception of 3.9, these borane catalysts give lower selectivities with enoxysilanes of propionic esters or ethylketones (< 80%) [796, 1302], Using 3.9 as a catalyst, high diastereo- and enantioselectivities are observed in the reactions of the E-ketene silylacetal of phenyl propionate with a,P-unsaturated aldehydes [788] and in the reaction of the enoxysilane of diethylketone with PhCHO [787] (Figure 6.95). All these results are interpreted by acyclic transition state models in which steric repulsions are minimized (Figure 6.95). 

Ketene silylacetals also react with a- or P-alkoxy- or -aminoaldehydes. Chelation control may take place in the reaction of ephedrine-derived ketene silylacetal 6.121 with p-benzyloxyaldehydes. Under TiCl4 catalysis, syn isomers are favored (Figure 6.98), but the reaction is highly selective only if the aldehyde is a-alkylated and the reagents are matched [1295], The results are interpreted through the intervention of a six-coordinate titanium complex 6.122 (Figure 6.98). 

There are only a few highly selective examples of conjugate additions of enoxysilanes or ketene silylacetals bearing chiral residues to electrophilic double... 

Most [3,3]-sigmatropic rearrangements take place thermally, and the Cope, oxy-Cope and Claisen rearrangements are among the most important rearrangements in this class. Important variants of the Claisen rearrangement include the Johnson modification via orthoesters, the Eschenmoser modification via ketene N,O-acetals, the Ireland modification via ketene silylacetals and the Corey modification via boron ester enolates [696], The aza-Claisen rearrangement has also seen... 

Si-transfer from oxygen to carbonIn the presence of a trialkylaluminum, particularly (CH3),AI, silyl ketene acetals rearrange at —78° to 20° to esters of trialkyl-silylacetic acid. This 1,3-rearrangemcnt of Si from oxygen to carbon is the reverse of the well-known Brook thermal rearrangement2 of Si from carbon to oxygen. But R AI does not rearrange trimethylsilyl enol ethers. 

Aminations which afford 6-aminocarboxylates are of interest in relation to monobactam antibiotics. A secondary aminomethyl group can be introduced at the -position of carboxylic esters by reaction of hexahydro-1,3,5-triazines with ketene silyl acetals in the presence of a catalytic quantity of trifluoromethanesulphonic acid (Scheme 25). The triazine (10) is considered to be converted into an N-silylated methyleneiminium salt which undergoes addition of the ketene silylacetal (11). 

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