Enol silyl acetal

UButylmethoxyphenylsilyl ethers (r-BMPSi ethers). In DMF in the presence of NfCjHj), this bromosilane reacts with primary, secondary, and tertiary alcohols to form silyl ethers in good yield, and also with some enolizable ketones to form enol silyl acetals. Selective silylation of primary alcohols is possible by use of CHjClj as solvent. The hydrolytic stability of these ethers is intermediate between that of t-butyldimethylsilyl ethers and that of t-butyidiphenylsilyl ethers. The most useful feature of this new protecting group is the selective cleavage by fluoride ion in the presence of other silyl ethers. 

Carreira developed a class of tridentate Schiff-base ligands derived from (R)-2-amino-2 -hydroxy-l,l -binaphthyl (NOBIN). The initially examined catalyst generated by treatment of the ligand with Ti(O Pr)4 did not show satisfactory catalytic performance in the aldol reaction of enol silyl acetal with aldehyde... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

As an alternative to lithium enolates. silyl enolates or ketene acetals may be used in a complementary route to pentanedioates. The reaction requires Lewis acid catalysis, for example aluminum trifluoromethanesulfonate (modest diastereoselectivity with unsaturated esters)72 74 antimony(V) chloride/tin(II) trifluoromethanesulfonate (predominant formation of anti-adducts with the more reactive a,/5-unsaturated thioesters)75 montmorillonite clay (modest to good yields but poor diastereoselectivity with unsaturated esters)76 or high pressure77. 

Addition of Nitronates, Enolates, Silyl Ketene Acetals and Cyanide Ion... 

With trimethylsilyl iodide 17 the 0,N-acetal 457 gives the iminium iodide as reactive intermediate this converts the enol silyl ether 107 a in situ into the Man-nich-base 669, in 81% yield, and hexamethyldisiloxane 7 [195]. On treatment of the 0,N-acetal 473 (or the N-silylated Schiff base 489) with TMSOTf 20 (or Zny, the intermediate iminium triflate adds to the ketene acetal 663 to give mefhoxytri-methylsilane 13 a and silylated / -amino esters such as 670, which are readily transsilylated by methanol to give the free / -aminoester [70, 196] (Scheme 5.61). 

Benzaldehyde can be condensed with the N-silylated urethane 671 and aUyltri-methylsilane 82 in the presence of trityl perchlorate to give, via an intermediate 0,N-acetal, the substituted urethane 672 in high yield [197]. 0,N-Acetals such as 673 condense with the enol silyl ether of acetophenone 653 in the presence of TMSOTf 20 to give the co-hydroxyurethane 674 in 94% yield [198] (Scheme 5.62). 

The N,N-bis(formylamido)acetal of cinnamaldehyde 687 condenses with the enol silyl ether of ethyl acetoacetate 724 a, in the presence of TiCl4, to give 79%... 

Lewis acids such as TiCl4 and SnCl4 induce addition of both silyl enol ethers and ketene silyl acetals to aldehydes.49... 

II and 12 indicate, the selenenylation of ketones can also be effected by reactions of enol acetates or enol silyl ethers. 

Claisen-type rearrangements of ester enolates, ketene acetals, and silyl ketene acetals... 

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

Instead of using an aldehyde for trapping the primarily formed enolate, there are also a few examples which involve an imino acceptor in the second anionic step. The Collin group used a lanthanide iodide-mediated reaction of a ketene silyl acetal... 

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

These authors also noted that the electron-donor ability of various derivatives of 2,2-dimesityl-1-phenylethenol decreases in the order enolate > enol > enol silyl ether > enol phosphate > enol acetate. As such, a simple derivatization allows the ready modulation of the electron-donor properties of ends. 

Addition of Ketene Acetals and Enoles In recent years, much attention has been given to the synthesis of optically active nitrogen-containing compounds, with the key step being the highly stereoselective nucleophilic addition of ketene silyl acetals to nitrones (Scheme 2.174). Similar to nitrone cyanations, in ketene silyl acetal reactions one observes an accelerating effect with thiourea derivatives (633). 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

Addition of ketene silyl acetals to aldehydes and ketones is also mediated by achiral palladium(ll) acetate-diphosphine complexes (Equation (109)).46S,46Sa Although the precise mechanism is still unclear, high catalytic activity may be ascribed to the intermediacy of palladium enolates. 

Chiral bis-phosphine acylplatinum complex 210 with a strong acid such as TfOH serves as an effective enantio-selective catalyst for aldol-type reactions of aldehydes with ketene silyl acetals (Equation (127)).486 The presence of water and oxygen in the catalyst preparation step is required to obtain the highly enantioselective catalyst. The intermediacy of a C-bound platinum enolate was suggested by IR and 31P NMR spectroscopies. 

An efficient preparation of hexahydro-isoxazolo[2,3- ]pyridin-2-ones relies on the anionic addition of nucleophiles at the electrophilic carbon of the nitrone followed by cyclization of the resulting Ar-oxide. As shown by results collected in Scheme 31, various nucleophiles can be engaged in the reaction and include enolates 95 <20020L3119> or 98 <2000BML1811>, silyl acetals 101 <2003TL2817>, or ynolates 103 <20020L3119> (Scheme 31). 

Reaction of 4a with TiCl4 was carried out in the presence of siloxyalkene 3 as nucleophile and the results are summarized in Table III. In the reaction with ketene silyl acetals 3a and 3e at -78 °C, y-ketoesters 15a and 15e were obtained instead of chloride product 8 which is a major product in the absence of 3. Formation of product 15 is likely to result from trapping of alkylideneallyl cation 5 with 3 at the sp2 carbon. In contrast, the reactions with silyl enol ethers 3f and 3g gave no acyclic product 15, but gave cyclopentanone derivatives 16-18. The product distribution depends on the mode of addition of TiCl4 (entries 4-7). 

The reaction with silyl enol ethers 3f and 3g gave only the [3 + 2] cycloadducts in comparison with effective formation of acyclic adduct 15 in the reaction with ketene silyl acetals 3a and 3e at lower reaction temperature. This can be explained by the reactivity of cationic intermediates 19 the intermediates from 3f and 3g are more reactive owing to lower stabilization by the oxy group than those from 3a and 3e, and react with the internal allene more efficiently to give the cycloadduct(s). Cyclic product 17a could be obtained at higher temperature via the reaction of 3a (entry 2). 

Various carbon nucleophiles, such as allylsilanes, allylstannanes, silyl enol ethers, ketene silyl acetals, organoaluminum compounds, and Grignard reagents were effective as carbon nucleophiles. 

The alkoxycarbenium ions generated by the cation pool method react with various carbon nucleophiles such as substituted allylsilanes and enol silyl ethers to give the corresponding coupling products in good yields. It should be noted that the reactions of alkoxycarbenium ion pools with such nucleophiles are much faster than the Lewis acid promoted reactions of acetals with similar nucleophiles. A higher concentration of the cationic species in the cation pool method seems to be responsible. 

Acetals of benzaldehydes may undergo EGA-catalyzed aldol reactions also with alkyl enol ethers, (22) (R = alkyl), as nucleophiles [31] but in contrast to the reaction with enol silyl ethers the threo isomer is favored in this case. 

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. 

Other Lewis acids can also effect conjugate addition of silyl enol ethers to electrophilic alkenes. For example, Mg(C104)2 catalyzes addition of ketene silyl acetals ... 

Aldol additions of silyl enol ethers and ketene silyl acetals can be catalyzed by (Cp)2Zr2+ species, including [(Cp)2ZrO-/-Bu]+ and (Cp)2Zr(03SCF3)2.39... 

Cerium, samarium, and other lanthanide halides promote addition of ketene silyl enol ethers to aldehydes.54 Imines react with ketene silyl acetals in the presence of Yb(03SCF3)3. Preferential addition to the imine occurs even in the presence of aldehyde... 

Table 1 summarizes the results of the reactions of ynoates (2a-c) with a silicon enolate (silyl ketene acetal) and a lithium enolate of methyl propionate (Eq. 1). Except for the reaction of 2c, Fe-Mont catalyzed exclusive 1,2-addition of silyl ketene acetal to 2a and 2b to give an adduct of 3 in high yields. However, even trimethyl silyl trifluoromethanesulfonate (TMSOTf), a generally applied homogeneous strong acid, failed to effect the addition reaction. 

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