A-Silyl esters

The addition of the lithium enolates of methyl acetate and methyl (trimelhylsilyl)acetate to ( + )-(S)-2-(4-methylphenylsulfinyl)-2-cycloalkenones gives, after desulfurization, (/ -substituted cycloalkenones. A higher level of selectivity is observed with the a-silyl ester enolate and in the cyclohexenone series13. The stereochemical outcome is rationalized by assuming attack on a ground-state conformation analogous to that in Section 1.5.3.2.1. 

Preparation of tris(trimethylsilyl) phosphite — Preparation of a silyl ester of a trivalent phosphorus acid for Michaelis-Arbuzov reaction... 

Silyl Ketene Acetal to a-Silyl Ester Isomerization... 

The trausmetallation of a-silylated ester lithium euolates by maguesium bromide aud subsequeut Peterson olefination provides a stereoselective synthesis of a,-unsaturated esters (equatiou 94). 

The C-Si bonds of aryl-, heteroaryl-, vinyl-, and allylsilanes are stable towards alco-holates or weak reducing agents, but can be cleaved under mild conditions by treatment with acids or fluoride to yield a hydrocarbon and a silyl ester or silyl fluoride. Several linkers of this type have been tested and have proven useful for the preparation of unfunctionalized arenes and alkenes by cleavage from insoluble supports. Typical loading procedures for these linkers are sketched in Figure 3.42. 

Dimethylalkenes.1 The readily available a-silyl esters, obtained by C-silylation of lithium ester enolates with 1, are useful precursors to trisubstituted alkenes, including 1,1-dimethylalkenes. 

On the other hand, methylaluminum bis(4-bromo-2,6-di-fert-butylphenoxide) can effect the a-alkylation of enol silyl ethers of a variety of ketones, esters and some aldehydes108. Use of the (Z-Bu)Me2Si group is recommended in the ketene silyl acetal substrates. Use of a less bulky Me3Si or Et3Si group leads to a mixture of monoalkylation products and rearranged a-silyl esters. 

The kinetics of these reactions are strongly affected by the conversion of the protic acid catalyst to a silyl ester as shown in equation 3. 

The product of a Ireland-Claisen rearrangement is a silyl ester. However, silyl esters generally are so sensitive toward hydrolysis that one usually does not attempt to isolate them. Instead, the silyl esters are hydrolyzed completely during work-up. Thus, Ireland-Claisen rearrangements de facto afford carboxylic acids and, more specifically, they afford y,5-unsaturated carboxylic acids. 

Fig. 17.32. Oxidative cleavage of an asymmetric ketone with complementary regiose-lectivities. Lactone A is obtained by Baeyer-Villiger oxidation of menthone [2-methyl-5-(l- methylethyl)cyclo-hexanone]. Alternatively, one may first convert menthone into the silylenol ether B and cleave its C=C double bond with ozone to obtain a silyl ester containing an a-methoxyhydroperoxide group as a second functional group (which resembles the unstable structural element of the so-called ether peroxides cf. Figure 1.38). The latter is reduced with NaBH4tothe hydroxylated silyl ester C. The hydroxycarboxylic acid is obtained by acid-catalyzed hydrolysis. It cyclizes spontaneously to give lactone D.

OL-Alkyl-OL, -unsaturated esters. a-Silyl esters can be obtained in >80% yield by reaction of lithium ester cnolatcs with this silane (10, 91 11, 247). Aldehydes and ketones react with the cnolatcs of these a-silyl esters to give adducts that undergo a Peterson elimination to form a-alkyl-a.p-unsaturatcd esters in which the (Z)-isomer predominates. 

Silylketene acetal (154) was directly prepared from a-silyl ester (153) in xylene at 230 C to give after acid hydrolysis the desired stereoisomer (155) in 72% overall yield with 6 1 stereoselectivity. Silylketene acetals are also obtained by TMS-Cl accelerated conjugate addition of cuprates. The latter method suffers presently from low diastereoselectivities, though it offers the attractive possibility of one-pot formation of two carbon-carbon bonds and three contiguous chiral centers (equation 15). 

Ethyl trimethylsilylacetate is stable to the usual manipulations, and can be stored in glass containers for years without change of physical and spectral properties IR (liquid film) cm 1720, characteristic of a-silyl esters The reported physical constants are bp 16-lTC (40 mm),... 

In certain cases, the C—Si bond of silanes can be converted to C—H. a-Silyl esters are reduced to esters with mercuric acetate and tetrabutylammonium fluoride, for example... 

Pinnick and coworkers " reported similar attempts to a-functionalize ethyl cyclopro-panecarboxylate (235) by treatment with base. Depending on the reaction conditions they were able to isolate the ketene acetal (236) and the a-silylated ester (237) as analogously reported by Ainsworth and coworkers ". ... 

Recently an alternative method has appeared which involves the addition of Grignard reagents to a-silyl esters, G. L. Larson, I. M. de Lopez-Cepero and L. E. Torres, Tetrahedron Lett., 1984, 25, 1673 P. F. Hudrlik and D. J. Peterson, Tetrahedron Lett., 1974, 1133. 

Diphenylmethylchlorosilane was purchased from Petrarch Systems, Inc., and distilled from calcium hydride (bp 85°C/0.1 mm) prior to use. A 187.5-mmol scale reaction using diphenylmethylchlorosilane purchased from Petrarch Systems and used without purification gave an 89% yield of the a-silyl ester. 

Rhodium cationic and zwitteiionic complexes proved to be superior catalysts for the hydroformylation of vinylsilanes, producing either a- or ff-silyl aldehydes depending on the reaction conditions [162], On the other hand, carbonylation of vinylsilanes in the reaction related to hydrocarboxylation and hydroesterification afforded P- and a-silyl esters in high yields (eq. (14) [163]). 

Gillies, M. B., Tender, J. E., Tanner, D., Norrby, P.-O. Quantum Chemical Calculations on the Peterson Olefination with a-Silyl Ester Enolates. J. Org. Chem. 2002, 67, 7378-7388. 

Hernandez, D., Larson, G. L. Chemistry of a-silyl carbonyl compounds. 9. Synthesis of tri- and tetrasubstituted olefins from a-silyl esters. J. Org. Chem. 1984, 49, 4285-4287. 

The synthetic utility of a-silyl esters has been amply demonstrated by several examples. The basis for this chemistry is the observation that ester lithium enolates can be directly C-silylated with methyldiphenylchlorosilane, a reagent which avoids the more common O-silylation153. The a-silyl-y-valerolactone 80 was converted in two steps and high yield to racemic ancepsenolide by condensation of its lithium enolate with decane 1,10-dicarboxaldehyde followed by isomerization to the endocyclic double bonds of the natural product154 (equation 160). Treatment of the a-silyl-y-butyrolactone 81 or 80 with a Grignard reagent followed by pyridinium chlorochromate (PCC) oxidation provides 4-oxo aldehydes and 1,4-diketones, respectively155 (equation 161). 

Insertion into Si-H bonds. a-Silyl esters are similarly obtained. From R2Si(Cl)H the products are readily converted into o-(alkoxysilyl)alkanoic esters. Heterocyclization. Formation of a-alkylidene lactams by carbonylation of alkynyl amines and cyclization of 2-allyloxybenzylamines with allylic rearrangement are reported. 

The a-silyl ester (234) behaves as a typical allylsilane in TiCl -catalysed reactions with a variety of electrophiles (a-halo-ethers, aldehydes, Michael acceptors) to give generally good yields of the trimethyl esters (235). ... 

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