Electrophilic silyl ketene acetals

Related Electrophilic Silyl Ketene Acetal Reagents. A... 

Mermerian AH, Fu GC (2003) Catalytic enantioselective synthesis of quaternary stereocenters via intermolecular C-acylation of silyl ketene acetals dual activation of the electrophile and the nucleophile. J Am Chem Soc 125 4050-4051... 

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). 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

SENAs derived from secondary AN are not involved in catalytic C,C-coupling reactions with silyl ketene acetals. This is possibly due to a decrease in both the effective concentration of the cationic intermediate (the steric effect) and its lower level of electrophilicity (see the lower entry in Table 3.23). 

Silyl enol ethers have also been used as a trap for electrophilic radicals derived from a-haloesters [36] or perfluoroalkyl iodides [32]. They afford the a-alkylated ketones after acidic treatment of the intermediate silyl enol ethers (Scheme 19, Eq. 19a). Similarly, silyl ketene acetals are converted into o -pcriluoroalkyl esters upon treatment with per fluoro alkyl iodides [32, 47]. The Et3B/02-mediated diastereoselective trifluoromethylation [48,49] (Eq. 19b) and (ethoxycarbonyl)difluoromethylation [50,51] of lithium eno-lates derived from N-acyloxazolidinones have also been achieved. More recently, Mikami [52] succeeded in the trifluoromethylation of ketone enolates... 

Further versatility of this approach has been realized with contrasting Lewis acid promoted additions of silyl ketene acetals, (191) to (194), to ethyl propynoate (Scheme 42). In fact, the tandem 1,4-conjugate addition-electrophile trapping protocol is feasible when titanium(IV) tetrachloride is employed. In situ functionalization of the intermediate titanate enoate (259), with select electrophiles, affords a-substituted enoates (260) to (262). On the other hand, the zinc iodide and zirconium(IV) tetrachloride protocols afford directly -y-alkoxycarbonyl-a-trimethylsilylenoates (263) and [2 + 2] adducts (264), respectively.100... 

The molecular mechanisms for the nucleophilic addition of lithium enolates and silyl ketene acetals to nitrones in the absence and in the presence of a Lewis acid catalyst to give isoxazolidin-5-ones or hydroxylamines have been investigated by DFT methods at the B3LYP/6-31G level.13 An analysis of the global electrophilicity of the reagents accounts for the strong electrophile activation of the Lewis acid-coordinated nitrone, (g) and the analysis of the local indices leads to an explanation for the experimentally observed regioselectivity. 

Imines are, preferably, used in the N-Boc-protected form less electrophilic N-allyl and N-benzyl imines gave unsuccessful results [36], The tert-butyldimethyl-silyl ketene acetals are the most suitable silyl ketene acetal substrates. It should be added that a low temperature is required to suppress an undesired uncatalyzed reaction that leads to racemates. 

The nucleophilic reactivities of silyl enol ethers (58, R1 = alkyl) and silyl ketene acetals (58, R1 = 0-alkyl) have been measured for the triphenylsilyl (R2 = H5) substrate, and its perfluoro analogue (R2 = F5), using benzhydrylium cations as reference electrophiles.224 The triphenyl compound is 10 times less reactive than its trimethyl equivalent, but the perfluorination causes the C=C nucleophilicity to drop by 3-4 orders of magnitude. The new compounds have been placed on scales of nucleophilicity taken from the literature. 

Hydrogen bond-promoted asymmetric aldol reactions and related processes represent an emerging facet of asymmetric proton-catalyzed reactions, with the first examples appearing in 2005. Nonetheless, given their importance, these reactions have been the subject of investigation in several laboratories, and numerous advances have already been recorded. The substrate scope of such reactions already encompasses the use of enamines, silyl ketene acetals and vinylogous silyl ketene acetals as nucleophiles, and nitrosobenzene and aldehydes as electrophiles. 

The observed rc-face differentiation of the electrophilic animation process was rationalized by the authors [14b]. NMR Nuclear Overhauser experiments agree with the ( -configuration of the O-silyl ketene acetals 35 and with a j-yn-periplanar disposition of the C -OSi and C2-Ha bonds. Electrophiles E+ , such as Lewis acids-co-ordinated DTBAD, attack 35 preferentially from the less hindered C(a)-Si (back) face (Scheme 17). 

Through a significant rc-backbonding interaction, the coordination of benzene to [Os] (1) serves both to activate the arene toward the electrophilic addition of dimethoxymethane (Table 1, entries 1-4) or 3-penten-2-one (entry 5) and to stabilize the resulting benzenium intermediate 8. If manipulated at low temperature (—40 °C), 8 can be trapped with either a silyl ketene acetal (entries 1, 4, and 5), 2-trimethylsiloxypropene (entry 2), or phenyllithium (entry 3) to yield the substituted 1,4-cyclohexadiene complex 9 [15]. This species can be oxi-... 

Silylated ketene acetals are more reactive than silyl enol ethers (Scheme 46), and the higher reactivity of cyclopentenes compared to cyclohexenes, which has already been reported for the hydrocarbon series (Scheme 41), is also observed for this class of compounds. The negative inductive effect of oxygen, which operates at the position of electrophilic attack, makes the bisenol ether (Scheme 46, right column, bottom) 20 times less reactive than the structurally analogous monoenol ether. 

Asymmetric electrophilic amination reactions using silyl ketene acetals 1 and di-tert-butyl azodicarboxylate (DBAD) finally lead to a-hydrazino 3 and ( )-a-amino acids 415. 

It is noteworthy that the level of the enantiomeric excess and the configuration of the a-chloro esters, were found to be not affected by the double bond configuration. Thus, with the same chiral auxiliary, i.e. D-(+)-glucose diacetonide, the electrophilic attack proceeds always on the same Si-face of the silyl ketene acetal whatever the E or Z configuration of the starting material (Fig. 8). 

The trienol silyl ether (70) reacts with carbon electrophiles at the e-position as illustrated in Scheme 44 73,147 Unexpectedly, the trienyl silyl ketene acetal (122) reacts with p-dimethylaminobenzoyl chloride and zinc bromide at the a-position to give the ester (123) as the only isolable product.134 It is not known at this time whether such a-selectivity is general for other aldol-type reactions of (122) or limited to acylations.148... 

Additive Pummerer reactions of the type described above using racemic a,P-unsaturated sulfoxides can be accomplished using the following electrophiles acyl chlorides [205,206], dithioacetic acid [207], acetic anhydride [208], mineral acids/alcohols [209], phosphorus pentachloride [210], silyl ketene acetals/zinc iodide [211], thionyl chloride [212], oxalyl chloride [213], trifluoroacetic acid and its anhydride [214-218], triflic anhydride/sodium acetate [219], and dichloroketene (see below). Selected recent examples of work in this area are presented here. 

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