Silyl esters, reactions

A newer method for the preparation of nitronic esters, namely utilizing the (9-trimethyl-silyl ester, has been reported and these are prepared by the reaction of alkylnitro compounds and (V,(V-bis(trimethylsilyl)acetamide. These nitronic esters also undergo cycloaddition with alkenes to produce isoxazolidines (equation 54) (74MIP41601, 74DOK109, 78ACS(B)ll8). 

Silyl esters are stable to nonaqueous reaction conditions. A trimethylsilyl ester is cleaved by refluxing in alcohol the more substituted and therefore more stable silyl esters are cleaved by mildly acidic or basic hydrolysis. 

On the other hand, syn-carboxylic acids are obtained from a deprotonation of the /5-silyl ester, giving the (E)-enolate, followed by reaction with different aldehydes and subsequent hydrogenolysis. No diastereomers of the aldol product are detected720. 

The use of HMDS (ca. 1.5 mmol) and saccharin (0.01 mmol) per mmol of substrate in refluxing dichloromethane or chloroform has been recommended (5) for easy silylation of carboxylic acids, including azetidin-2-one-4-carboxyIic acids. Clear solutions result, i.e., no ammonium salts are present at completion of the reaction, and consequently the silyl esters can be obtained by direct distillation, or merely by evaporation of solvent. 

A solution of LDA (11 mmol) in THF (30 ml) was cooled to -78°C, and HMPA (CAUTION—CANCER SUSPECT AGENT) (3 ml) then added. To this solution was added dropwise 3-acetoxyoct-l-ene (10 mmol), and then TBDMSC1 (11 mmol) in THF (2 ml) over 5 min. The pale yellow solution was stirred at -78°C for an additional 2 min, and the reaction mixture was allowed to warm to 25DC over 30min. It was stirred at this temperature for a further 2 h, and then quenched with water and pentane. The combined pentane extracts were concentrated, the crude oily silyl ester was dissolved in THF (25 ml) and dilute aqueous HC1 (5 ml, 3 m) and the solution was then stirred for 45 min at 25 °C to complete hydrolysis. The mixture was then poured into aqueous sodium hydroxide (30 ml, I m) and... 

The use of silylated monomers is an interesting alternative method of aromatic polyester synthesis since the silylated gaseous by-products cannot participate in the reverse reaction, shifting polyesterification toward polymer formation. Reactions between silyl esters and acetates (Scheme 2.23) and reactions between silyl ethers and acid chlorides (Scheme 2.24) have been applied to the synthesis of linear265-267 and hyperbranched wholly aromatic polyesters202,268 269 (see Section 2.4.5.2.2). 

The fe-ester derivatives of trithiophosphinic acids, RP(S)(SR )2, have also been studied and, similar to the metal and ammonium salts, show enhanced thermal stability compared to their parent acids. Trithiophosphonic acid Zj zA (tr im e t lr y 1 s i 1 y 1) esters have been synthesised from organo-/u.v(trim-ethylsilyl)phosphanes with elemental sulfur in toluene (Equation 40).53 These 6z,s(silyl esters) can be readily converted into the parent trithiophosphinic acid by a very slow, controlled reaction with water or methanol.53... 

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

The other major approach toward overcoming the "alkyl transfer" difficulty of the Abramov reaction involves the use of silyl esters of the trivalent phosphorus acids. Unlike carbon, silicon does not have the stereochemical restraints associated with ordinary alkyl groups for intramolecular transfer.211 The preparation of mixed alkyl—silyl esters of trivalent phosphorus acids paved the way for the Abramov reaction to be of general utility.204 208 212 An example is shown in Equation 3.14. 

As with other reactions, silyl esters of phosphorus acids constitute an important and useful category of reagents for conjugate addition reactions. With aldehydes, ketones, and esters, the silyl ester linkage is transferred to the carbonyl oxygen, facilitating the completion of the reaction, generating the free carbonyl or ester upon workup with a protic solvent (Equation 3.25). 

Silyl esters of trivalent phosphorus acids have been used successfully in conjugate addition reactions using acrylates,393 395 nitriles,394 amides,396 397 ketones and aldehydes,398-404 and nitro compounds.387... 

Prishchenko, A.A., Livantsov, M.V., Kustrya, D.N., Grigorev, E.V., and Luz-ikov, Y.N., Reaction of l,3,5-triethylhexahydro-l,3,5-triazine with trimethyl-silyl esters of trivalent phosphorus acids, Zh. Obshch. Khim., 64, 1575, 1994. 

The formation of the latter compounds can be attributed to the result of the direct attack of the nucleophile R on the a- or p-carbon atoms of SENAs after elimination of the corresponding protons. However, it is most likely that the reaction proceeds through nitrile oxides or conjugated nitrosoalkenes (see Scheme 3.93). This interpretation is evidenced by generation of silyl esters of hydroxamic acids R CONHOSi as by-products. The reactions with more saturated solutions give the latter compounds as the major products. 

Two procedures were developed for C,C-coupling reactions of silyl esters of primary AN. One approach involves two steps and the synthesis of intermediate SENAs according to standard procedures. Another procedure is based on the one-pot reaction of AN with the DBU/TBSOTf system in a ratio of 1 1.1 followed by the addition of silyl ketene acetal and a catalytic amount of TBSOTf. 

The isomerization of an O-silyl ketene acetal to a C-silyl ester is catalyzed by a cationic zirconocene—alkoxide complex [92], This catalysis was observed as a side reaction in the zirconocene-catalyzed Mukaiyama aldol reactions and has not yet found synthetic use. The solvent-free bis(triflate) [Cp2Zr(OTf)2] also catalyzes the reaction in nitromethane (no reaction in dichloromethane), but in this case there may be competitive catalysis by TMSOTf (cf. the above discussion of the catalysis of the Mukaiyama aldol reaction) [91] (Scheme 8.51). 

This method can also be applied to silyl enol ethers of homologous unsaturated ketones as well as of unsaturated aldehydes or esters [85-87]. While unmodified unsaturated esters give only the corresponding aldehydes without cyclization under tandem hydroformylation/aldol reaction conditions, the corresponding silylated ester enolates smoothly cyclize in a tandem hy-droformylation/ Mukaiyama aldol reaction (Scheme 32) [85-87]. 

Tab. 3.2. Diastereoselectivity in the aldol reactions between ( )- or (Z)-/ -silyl ester enolates and aldehydes (Scheme 3.7).

The order of those steps can be reversed. The synthesis of the homologous compound cefquinome (24-6) starts by protecting the carboxyl group in cefotaxime (24-1), itself a potent antibiotic as its silyl ester (24-2), by reaction with... 

The deacetyl compound (26-6) is now used for the direct production of cephalexin (25-3) as well as several other related agents that incorporate similar amide side chains. For example, reaction of the protected 7-ADCA derivative (27-2) with the fert-BOC amide from D- flra-hydroxyphenylglyeine (27-1) by the mixed anhydride method gives the amide (27-3). Serial scission of the tert-BOC group and the silyl ester affords the antibiotic cefadroxyl (27-4) [32]. Exactly the same sequence starting... 

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