Acetals, acid catalyzed with silyl enol ethers

Montmorillonite KIO also catalyzed the Mukaiyama aldol reactions of aldehydes with silyl enol ethers or ketene silyl acetals in neat water commercially available montmorillonite KIO can be used without the need for ion-exchange processes and can be reused again after thermal activation. Even hydrates of aldehydes such as glyoxyhc acid can be used directly in this reaction. 

Reductive aldol reaction of a,(5-unsaturated esters and enones with aldehyde mediated by a transition metal hydride complex and a hydride source, such as hydrosilane, is a versatile process to produce p-hydroxy carbonyl compounds (Scheme 15a) [21]. This reaction is thought to be an alternative transformation of Lewis acid-catalyzed Mukaiyama-type aldol reaction with silyl enol ethers or silyl ketene acetals (Scheme 15b). 

The Mukaiyama aldol reaction refers to Lewis acid-catalyzed aldol addition reactions of silyl enol ethers, silyl ketene acetals, and similar enolate equivalents,48 Silyl enol ethers are not sufficiently nucleophilic to react directly with aldehydes or ketones. However, Lewis acids cause reaction to occur by coordination at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

The reactions proceeded efficiently under mild conditions in short time. The silyl enol ethers reacted with the activated acetals or aldehydes at -78 °C to give predominant erythro- or threo-products [136, 137] respectively. In the same manner, the aldol reaction of thioacetals, catalyzed by an equimolar amount of catalyst, resulted in <-ketosulfides [139] with high diastereoselectivity. In the course of this investigation, the interaction of silyl enol ethers with a,]3-unsaturated ketones, promoted by the trityl perchlorate, was shown to proceed regioselec-tively through 1,2- [141] or 1,4-addition [138]. The application of the trityl salt as a Lewis acid catalyst was spread to the synthesis of ]3-aminoesters [142] from the ketene silyl acetals and imines resulting in high stereoselective outcome. 

At this point, consideration was next accorded to proper introduction of the pair of substituents as in 34. As expected, the regiocontrolled introduction of a methyl group proved not to be problematic, and lithium diisopropylamide came to be favored as the base. The p isomer 29 predominted by a factor of 5 1 over the a isomer for the usual steric reasons (Scheme 5). To reach silyl enol ether 31, it was most efficient and practical to react the 29/30 mixture with chlorotrimethylsilane under thermodynamic conditions. This step proved to be critical, as it allowed for implementation of the Lewis acid-catalyzed acetylation of 31 under conditions where the benzyloxy substituent was inert. Equally convenient was the option to transform the modest levels of enol acetate produced competitively back to starting ketone by saponification with methanolic potassium hydroxide. 

A recent notable finding in this field is Mukaiyama aldol reactions in aqueous medium (THF H20 = 9 1) catalyzed by metal salts. Lewis acids based on Fe(II), Cu(II), and Zn(II), and those of some main group metals and lanthanides are stable in water. Remarkably, the aldol reaction shown in Sch. 29 occurs more rapidly than the hydrolysis of the silyl enol ether [137]. In the presence of surfactants (dodecyl sulfates or dodecane sulfonate salts), reactions of thioketene silyl acetals with benzaldehyde can be performed in water [138]. 

Enantiomerically pure 3-oxo-8-oxabicyclo[3.2.1]octyl-2-yl derivatives were obtained by [4 -h 3] cycloaddition of furan with chiral 1,2-dioxyallyl cation engendered in situ by acid-catalyzed heterolysis of enantiomerically pure, mixed acetals derived from 1,1-dimethoxy-acetone and enantiomerically pure, secondary benzyl alcohols [203]. For instance, mixed acetal 439 is converted into the silyl enol ether 440. In the presence of a catalytic amount of trimethylsilyl triflate, 440 generates a cationic intermediate that adds to furan at - 95°C, giving... 

The catalyzed reaction of enol ethers with carbonyl compounds (Scheme 1) has become an important reaction in synthesis. Compared to the metal enolate reactions (Part 1, Volume 2), the catalyz enol ether reactions offer the following distinct differences. Enol ethers are often isolable, stable covalent compounds, whereas the metal enolates are usually generated and used in situ. Under Lewis acid catalyzed conditions, a number of functional equivalents such as acetals, orthoesters, thioacetals, a-halo ethers and sulfides can participate as the electrophilic components, whereas many of them are normally unreactive towards metal enolates. In synthesis, enol ether reactions now rival and complement the enolate reactions in usefulness. Enol silyl ethers are particularly useful because of their ease of preparation, their reasonable reactivity and the mildness of the desilylation process. 

Lewis acid catalyzed aldol coupling of silyl enol ethers with substituted cyclohexanone acetals showed an excellent preference for equatorial attack (95-l(X)%). In accord with this general rule, additions of a silyl enol ether to equatorially or axially substituted chiral spiroketals derived from -menthone gave 00% equatorial attack and formation of a single one of the four possible diastereoisomers (Scheme 9) 3, 4 -pjjjg methodology, followed by protection of the hydroxy group (X = OTHP, (XIPh.i) and alkaline removal of the chiral auxiliary was used for the synthesis of several natural products. ... 

Michael Reactions. The Michael reactions of silyl enol ethers or ketene silyl acetals with a,/3-unsaturated carbonyl compounds are catalyzed by Sc(OTf)3 to give the corresponding 1,5-dicarbonyl compounds in high yields after acid work-up (eq 5). When the crude adducts were worked up without acid, the synthetically valuable silyl enol ethers could be isolated. The catalyst can be recovered almost quantitatively and reused. Sc(OTf)3 also catalyzes 1,4-addition of PhMe2Si-ZnMe2Li to enones in the presence of 3 mol % of Me2Cu(CN)Li2. ... 

The addition of 1,4-benzoquinone was also found to prevent olefin isomerization in a number of ruthenium-catalyzed olefin metathesis reactions of allylic ethers (Scheme 12.32) [57]. When the siloxy ether 107, which bears a ds-olefin, was treated with Ru catalyst 3 (5 mol%) in CD2CI2 at 40 C for 24 h, a mixture of 107 and the corresponding tram isomer of 107 was observed in 19% yield, while 81% of the reaction mixture was the isomerized silyl enol ether product 108. The addition of 1,4-benzoquinone or acetic acid completely suppressed olefin migration, and mixtures of cis- and tram-105 were the major products (> 95%). Phenol, another common additive in olefin metathesis reactions, failed to inhibit olefin migration, and enol ether 108 was formed as the major product. 

Oxidation of Silyl Compounds. MTO-catalyzed oxidization of silyl enol ethers with hydrogen peroxide yields a-hydroxyketones in high yield. The reactions were conducted with pyridine as the amine additive in acetic acid (eq 22). 

Successful examples of the Mukayama aldol reaction include the use of the thermally stable tris(pentafluorophenyl)borane Lewis acid. Yamamoto and coworkers reported that 2 mol% of (C6Es)3B smoothly catalyzes the Mukaiyama-aldol reaction of various silyl enol ethers or ketene silyl acetals with aldehydes (Equation 45). ... 

Optimization studies revealed that cycloaddilions of cyclic silyl enol ethers with ethyl propiolate (21a), promoted by 2 mol % Tf2NH, occurred at ambient temperature to generate cyclobutenes 22a-C in good yields. Finally, exploratory studies aimed at further optimizing the cyclobutane forming process showed that the organic acid catalyzed cycloaddition reaction could be successfully performed in various solvents, such as toluene, acetonitrile, dichloroethane, and ethyl acetate (Table 4.9). The reactions of propiolate took place even under solvent-free conditions. Although reactions of acrylates normally required careful control of temperature below —40 °C, in ethyl acetate these cycloadditions took place at more conveniently accessed ambient temperatures. 

AldolCondensations. Cation-exchanged montmorillonites accelerate the aldol condensation of silyl enol ethers with acetals and aldehydes. Similarly, the aldol reaction of silyl ketene acetals with electrophiles is catalyzed by solid-acid catalysts. Neither report discussed the use of iron montmorillonite for these reactions however, some reactivity is anticipated. 

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