Trimethylsilyl ketene acetals

Trimethylsilyl enol ethers, 94,133 Trimethylsilyl ketene acetals, 112-113 3-Trimethylsilyl -lactam, 71 Trimethylsilyl lithium, 51-2... 

Nitrobenzene reacts with the O-trimethylsilyl ketene acetal 663 in the presence of tris(dimethylamino)sulfur(trimefhylsilyl)difluoride (Me2N)3S(Me3SiF2) (TASF) to give the O-silylated adduct 1007 a, which can be oxidized in situ, e. g. by bromine, to give the 4-substituted nitrobenzene 1008 in an overall yield of 79% [87] (Scheme 7.28). With less hindered ketene-acetals, however, mixtures of ortho- and para-substituted nitrobenzenes are obtained. Yet, on reaction of 4-fluoronitroben-zene with the cyclic O-trimethylsilyl ketene acetal 1009 the ortho-substitution product 1010 is obtained in 79% yield [87]. 

The trimethylsilyl ester of a-trimethylsilyacetic acid 1613 is converted by LDA and TCS 14 into the C,0,0-tris(trimethylsilyl)ketene acetal 1614 in 91% yield. Reaction of 1614 with benzaldehyde in the presence of ZnBr2 proceeds via 1615 to afford a high yield of trimethylsilyl cinnamate 1616 [18], which gives on work-up free ( )-cinnamic acid in nearly quantitative yield (Scheme 10.7). In contrast, reaction of the lithium salt of 1613 with benzaldehyde then acidic hydrolysis affords a 1 1 mixture of ( )- and (Z)-cinnamic acid in 86% yield [18]. 

Ireland-Claisen rearrangement of O-allyl-O -trimethylsilyl ketene acetals... 

Similar chelation effects are present in a-alkoxymethyl derivatives. Magnesium enolates give predominantly the Z-enolate as a result of this chelation. The corresponding trimethylsilyl ketene acetals give E,Z mixtures.248... 

Tocopheryl)propionic acid (50) is one of the rare examples that the o-QM 3 is involved in a direct synthesis rather than as a nonintentionally used intermediate or byproduct. ZnCl2-catalyzed, inverse hetero-Diels-Alder reaction between ortho-qui-none methide 3 and an excess of <2-methyl-C,<9-bis-(trimethylsilyl)ketene acetal provided the acid in fair yields (Fig. 6.37).67 The o-QM 3 was prepared in situ by thermal degradation of 5a-bromo-a-tocopherol (46). The primary cyclization product, an ortho-ester derivative, was not isolated, but immediately hydrolyzed to methyl 3-(5-tocopheryl)-2-trimethylsilyl-propionate, subsequently desilylated, and finally hydrolyzed into 50. 

Due to their electron deficient character, pyridines are susceptible to nucleophilic attack. Rudler et al. has studied the reaction of pyridines with bis(trimethylsilyl)ketene acetals <06TL4553 06TL4561>. In one instance, they examine the reaction of... 

The PET-oxidative cyclization of unsaturated O-alkyl-O-trimethylsilyl ketene acetals 23 and 27 yields cyclic esters 24, 25, and 28, accompanied by the formation of considerable amounts of non-cyclic esters 26 and 29, respectively [89], The cyclization mode is found to be in accordance with free radical cyclizations of the appropriate esters 26 and 29, performed by heating with organic peroxides [90]. Since organic electrochemistry can be used to oxidize... 

Rearrangement of allyl trimethylsilyl ketene acetal, prepared by reaction of allylic ester enolates with trimethylsilyl chloride, to yield Y,5-unsaturated carboxylic a-cids. The Ireland-Claisen rearrangement seems to be advantageous to the other variants of the Claisen rearrangement in terms of E/Z geometry control and mild conditions. 

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. 

The use of an unsubstituted heterocycle as a precursor in synthetic reactions is relatively rare. For this reason, the reaction described in Equation (120) is shown. Unsubstituted pyrazine 335 is first treated with bis(trimethylsilyl)-ketene acetals, followed by treatment with methyl chloroformate. The result is the nonaromatic products 336 <2005EJO3724, 2005TL3449>. 

A stereoselective Mukaiyama-type aldol reaction of bis(trimethylsilyl)ketene acetals produces silyl aldols with syn stereoselectivity, predominantly due to steric effects.23... 

For a stereoselective aldol of bis(trimethylsilyl)ketene acetals,23 see Reactions of Ketenes earlier. 

Twenty years have passed since DuPont announced a startling new process for polymerization of methacrylate monomers [1]. The method uses a trimethylsilyl ketene acetal initiator catalyzed by nucleophilic anions. It operates at 80 °C and gives unprecedented control over polymer chain architecture (Scheme 1). 

As shown in Scheme 1, GTP converts methacrylate monomer to a polymer with one end group corresponding to the R on the initiator and the other end a trimethylsilyl ketene acetal. If the initiator contains a vinyl group not reactive to GTP, a macromonomer results [8]. The silyl ketene acetal end can be used to initiate another monomer, for example butyl methacrylate, to give... 

E)-a.,fl-Unsaturated acids. Zinc bromide is the most effective Lewis acid for promoting a reaction of C,0,0-tris(trimethylsilyl) ketene acetal (1) with aldehydes (but not ketones) to form a,p-unsaturated acids. The ketene acetal can be prepared as shown in equation (I). 

The use of substituted pyridines in organic synthesis has broad application. The activation of the pyridine ring toward nucleophilic attack is well known in the literature. The products of such reactions are often dihydropyridines which can serve as intermediates in more complex synthetic strategies. Rudler and co-workers have reported on the nucleophilic addition of bis(trimethylsilyl)ketene acetals to pyridine (26). The 1,4-addition product 27 was then cyclized with iodine to afford bicycle 28 in 90% overall yield <02CC940>. Yamada has elegantly shown that facial selectivity can be achieved and chiral 1,4-dihydropyridines accessed in high yield and de (29—>30) <02JA8184>. 

Roush WR, Hall SE (1981) Studies on the total synthesis of chlorothricol-ide stereochemical aspects of the intramolecular Diels-Alder reactions of methyl undeca-2,8,10-trienoates. J Am Chem Soc 103 5200-5211 Rudler H, Denise B, Xu Y, Parlier A, Vaissermann J (2005) Bis(trimethylsilyl)-ketene acetals as C,0-dinucleophiles one-pot formation of polycyclic y-and 8-lactones from pyridines and pyrazines. Eur J Org Chem 3724-2744 Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T (2004) Concise synthesis of anti-HIV-1 Active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-michael addition. J Org Chem 69 2760-2767... 

Table 2 Oxazocines 109 synthesized from pyridines, bis(trimethylsilyl)ketene acetals, and methyl chloroformates <2002CC940, 2005EJO3724>...

Direct nucleophilic addition of potassium enolates derived from bis(trimethylsilyl)ketene acetals to aromatic chromium-complexed aromatic ethers affords meta substituted products (Scheme 124). A very high degree of asymmetric induction is obtained upon reaction of chiral arene chromium tricarbonyl complexes. For example, alkylation of complex (80)gave (81)afterdecomplexation(Scheme 125). ... 

This method was further improved when it was found that readily available allyl esters of the general formula 493 could also be involved in Claisen rearrangements via intermediate formation of ketene derivatives such as lithium enolates 494 or trimethylsilyl ketene acetals 495 (the Ireland-Claisen variant" ). Moreover, rearrangement of these substrates into unsaturated acids 496 occurred easily at room temperature or below. This was in striking contrast to all previous versions of the Claisen rearrangement, which required heating at elevated temperatures (140-160 °C). The Ireland (silyl ketene acetal) variant of... 

Silylketene acetals react with imines under acidic conditions (Scheme 22). With N-alkylimines in the presence of a stoichiometric amount of TiCU, -lactams are formed in good yields. N-Aryl- " and N-trimethyl-silylimines also react under acidic conditions but yield only open-chain products. On the other hand, bis(trimethylsilyl)ketene acetals yield 3-lactams with both N-alkyl- and N-aryl-imines (Scheme 22). °... 

Yamamoto and co-workers found that 27 is an excellent chiral promoter not only for the aza Diels-Alder reaction of aldimines [40] but also for the stereoselective aldol-type reaction of aldimines with ketene silyl acetals [55]. The reaction of (5)-benzyli-dene a-methylbenzylamine with trimethylsilyl ketene acetal derived from terf-butyl acetate in the presence of (R)-27 produces the (R) adduct in > 92 % diastereomeric excess (de), whereas reaction with (5)-27 gives the adduct in 74 % de. In a similar way, (5)-butylidene a-methylbenzylamine, an aliphatic imine, can be converted to the (R)-)3-amino ester in 94 % de by use of (R)-27 (Eq. 73). 

During the course of further mechanistic studies of this reaction, the reaction rate was found to be dramatically accelerated by incorporation of the silicon atom within a four-membered ring (Sch. 64) [106a], The reaction of trimethylsilyl ketene acetal 89a with 90 requires heating at 150 °C, and less than 25 % 91a is formed after 24 h. In marked contrast, the silacyclobutane counterpart 89b reacts completely and clearly with 90 within 24 h at 27 °C to furnish 91b quantitatively. This implies that reaction proceeds by way of a pentavalent organosilicon species in which a boat-like transition state is preferred. 

Olefinic pyrazines like 108 were shown to react with QH in the superacid TfOH to give anti-Markovnikov addition products like 109 <050L2505>. The orientation observed is presumed to be due to the multiply charged heterocycle adjacent to the olefin. Pyrazine o-quinodimethanes underwent Diels-Alder condensation with meso-tetraarylporphyrins to give new jt-extended porphyrins <05TL2189>. A one-pot formation of polycyclic - and -lactones like 111 was developed using the reaction of pyridine and pyrazine (110) with bis(trimethylsilyl)ketene acetals. Many of them were characterized by X-ray <05EJO3724>. 

Table XIX shows the results of reactions of silyl ketene acetals derived from propionates with crotonate, cinnamate, sorbate, and fumarate in the presence of aluminum ion-exchanged montmorillonite (Al-Mont) (62). The reactions proceeded at low temperatures. The Michael products could be isolated in the unstable form of a trimethylsilyl ketene acetal in good yield owing to an easy work-up procedure (removal of the solid catalyst). It is noteworthy that the montmorillonite-induced Michael addition to a polyenoate occurred regioselectively in a 1,4-fashion in the case of methyl sorbate (Table XIX, Entry 4), the preference for 1,4-addition (98%) over 1,6-addition (2%) is notable because the addition of a lithium enolate (a conventional...

As another example of novel catalysis employing montmorillonite, the clay was found to show excellent catalytic activity for the addition reaction of trimethylsilyl ketene acetal to a, -acetylenic esters (ynoates), which contrasted strikingly with the reactions induced by a homogeneous acid catalyst, trimethylsilyl triflate (TMSOTf), as well as the addition reactions of lithium enolates with ynoates [Eq. (17)] (89). Table XXIII summarizes the results of the reactions of the silicon and lithium enolates of methyl propionate (21) with ynoates (22a-c). Except for the reaction of 22c, ferric ion-exchanged montmorillonite (Fe-Mont), which is more acidic than Al-Mont, catalyzed exclusive 1,2-additions of trimethylsilyl ketene acetal to 22a and 22b to give 23 in... 

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