Oxygen ketene enolates

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. 

Entries 4 and 9 are closely related structures that illustrate the ability to control stereochemistry by choice of the Lewis acid. In Entry 4, the Lewis acid is BF3 and the (3-oxygen is protected as a f-butyldiphenylsilyl derivative. This leads to reaction through an open TS, and the reaction is under steric control, resulting in the 3,4-syn product. In Entry 9, the enolate is formed using di-n-butylboron triflate (1.2 equiv.), which permits the aldehyde to form a chelate. The chelated aldehyde then reacts via an open TS with respect to the silyl ketene acetal, and the 3,4-anti isomer dominates by more than 20 1. 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

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. 

As previously mentioned, allenes can only be obtained by 1,6-addition to acceptor-substituted enynes when the intermediate allenyl enolate reacts regioselectively with an electrophile at C-2 (or at the enolate oxygen atom to give an allenyl ketene acetal see Scheme 4.2). The regioselectivity of the simplest trapping reaction, the protonation, depends on the steric and electronic properties of the substrate, as well as the proton source. Whereas the allenyl enolates obtained from alkynyl enones 22 always provide conjugated dienones 23 by protonation at G-4 (possibly... 

Song and co-workers have taken a variety of aldehydes 344 and treated them with A -adamantyl carbene 1 and trimethylsilyl ketene acetal 345 to produce Mukaiyama aldol products 346 in good yield (Eq. 34) [170], The carbene presumably acts as a Lewis base to activate the silicon - oxygen bond in order to promote reactivity of the enol silane. The catalyst loading can be reduced to as low as 0.05 mol% without a change in yield. 

Among the facts supporting this mechanism (which is an A-Se2 mechanism because the substrate is protonated in the rate-determining step) are (1) lsO labeling shows that in ROCH=CH2 it is the vinyl-oxygen bond and not the RO bond that cleaves 497 (2) the reaction is subject to general acid catalysis 498 (3) there is a solvent isotope effect when D2O is used.498 Enamines are also hydrolyzed by acids (see 6-2) the mechanism is similar. Ketene dithioacetals R2C=C(SR )2 also hydrolyze by a similar mechanism, except that the initial protonation step is partially reversible.499 Furans represent a special case of enol ethers that are cleaved by acid to give 1,4 diones. Thus... 

The use of aryl-A3-iodanes for C-heteroatom bond formation at the a-carbon atoms of ketones and / -dicarbonyl compounds, and related transformations of silyl enol ethers and silyl ketene acetals, has been exhaustively summarized in recent reviews (Scheme 27) [5,8]. Reactions of this type are especially useful for the introduction of oxygen ligands (e. g., L2 = OH, OR, OCOR, 0S02R, OPO(OR)2), and have been extensively utilized for the synthesis of a-sulfonyl-oxy ketones and a-hydroxy dimethyl ketals. 

As expected according to the HSAB principle, hard electrophiles such as silyl halides and triflates react at the enolate oxygen atom to form allenyl ketene acetals, while soft electrophiles such as carbonyl compounds attack at C2. Only allylic and propargylic halides react regioselectively at G4 of the allenyl enolate to give substituted conjugated dienes. 

The answer is both For the Li enolate, the usual rule makes OU of lower priority than oMe, so it s E, while the silyl enol ether (or silyl ketene acetal ) has OSi of higher priority than OMe, so it s Z. This is merely a nomenclature problem, but it would be irritating to have to reverse all our arguments for lithium enolates simply because lithium is of lower atomic number than carbon. So, for the sake of consistency, it is much better to avoid the use of Eand Z with enolates and instead use cis and trans, which then always refer to the relationship between the substituent and the anionic oxygen (bearing the metal). 

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. 

The capability of the highly oxygenated carbohydrate auxiliaries to coordinate the counter-ion of the enolate allows the formation of chiral chelate complexes with a restricted flexibility of the enolate moiety. The cation complexation also increases the tendency of the carbohydrate to react as a leaving group. It has been found [153] that the enolate 204 generated by deprotonation of the carbohydrate linked ester 203 with LDA underwent an elimination of the carbohydrate moiety generating the alcohol chelate complex 205 and the ketene 206 (Scheme 10.67). 

In this context, the E- and Z-nomenclature of ester enolates and silyl ketene acetals refers to their geometries where the carbonyl oxygen given highest priority irrespective of priority by CIP Cahn-Ingold-Prelog) rules. 

Pt(II). Fujimura has developed a Pt(II)-catalyzed process for the addition of iso-butyrate-derived silyl ketene acetal 97 to aldehydes (Eq. (8.27)) [43]. The process utilizes a readily available Pt(Il) complex (98) that is generated in situ and can be easily handled in the laboratory [44]. In the presence of 5 mol% each of 98, triflic acid, and lutidine, 97 undergoes addition to aldehydes to afford a mixture of tri-methylsilyl-protected 99 and free alcohol 100 products in up to 95% ee. A thorough examination of the reaction conditions and their effect on the product selec-tivities has revealed that the addition of water and oxygen to the catalyst mixture leads to significant improvement in the optical purity of the products. A number of spectroscopic studies by P NMR and IR has led Fujimura to postulate that the reaction involves a carbon-bound platinum enolate intermediate in the catalytic cycle. 

Enol ethers, alkenes with a more remote oxygen atom, ketene acetals or esters of unsaturated alcohols undergo addition of dibromocarbene to give the corresponding 1,1-dibromocyclo-propanes, often in high yield. Some of these products are of limited stability, which creates problems with their isolation and purification. 

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