A-Trimethylsilylation

Another o-aminobenzyl anion equivalent is generated by treatment of A-trimethylsilyl-o-toluidinc with 2.2 eq. of n-butyllithium. Acylation of this intermediate with esters gives indoles[2]. This route, for example, was used to prepare 6.2D, a precursor of the alkaloid cinchonamine. 

The presence of activating substituent on the carbocyclic ring can, of course, affect the position of substitution. For example, Entries 4 and 5 in Table 14.1 reflect such orientational effects. Entry 6 involves using the ipso-directing effect of a trimethylsilyl substituent to achieve 4-acetylation. 

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. 

The ability to promote /S elimination and the electron-donor capacity of the /3-metalloid substituents can be exploited in a very useful way in synthetic chemistry. Vinylstannanes and vinylsilanes react readily with electrophiles. The resulting intermediates then undergo elimination of the stannyl or silyl substituent, so that the net effect is replacement of the stannyl or silyl group by the electrophile. An example is the replacement of a trimethylsilyl substituent by an acetyl group by reaction with acetyl chloride. 

From a trimethylsilyl glycoside TMSOTf or TFA or BF3-Et20, CH3OCH2OCH3, 54-66% yield." ... 

From a trimethylsilylated triol MeOPhCHO. TMSOTf, CH2CI2, —78°, 5 h, 96% yield. ... 

In a similar example, a trimethylsilyl group was cleaved with NaOH, MeOH, H2O in the presence of a triethylgermyl group. The latter group can also be cleaved with methanolic HCIO4 the rate increases with increasing electron density. ... 

For example in the so-called Mukaiyama aldol reaction of an aldehyde R -CHO and a trimethylsilyl enol ether 8, which is catalyzed by Lewis acids, the required asymmetric environment in the carbon-carbon bond forming step can be created by employing an asymmetric Lewis acid L in catalytic amounts. 

Metalated epoxides are a special class of a-alkoxy organometallic reagent. Unstabilized oxiranyl anions, however, tend to undergo a-elimination. On the other hand, attempts to metalate simple unfunctionalized epoxides may lead to nucleophilic ring opening. The anion-stabilizing capability of a trimethylsilyl substituent overcomes these problems. Epoxysilanes 22 were... 

Aldol reaction of the a-trimethylsilylated enolate 9 with aldehydes provides nearly equal amounts of chromatographically separable ( )- and (Z)-isomers of iron-acyl complexes 11 via silyloxide elimination from the intermedate aldolate 10 (Table 3). This methodology has been the most commonly employed entry to the (Z)-isomer series. 

Optically pure vinylglycine derivatives 3 can be prepared by reacting lithiated (2aldol adducts 212. Hydrolysis of the adduct, followed by heating in 5N hydrochloric acid, effected ester hydrolysis and Peterson elimination to give the vinylglycine derivatives. 

The addition of methyllithium to -alkoxy-a-(trimethylsilyl)-of/ unsaturated sulfones, 3-alkoxy-5-phenyl-l-phenylsulfonyl-l-(trimethylsilyl)-l-pentene and subsequent desilylation gives syn-products. The syn to anti diastereoselectivity is generally high and essentially independent of the nature of the y-alkoxy substituent8-13. 

The addition reactions of alkyllithium-lithium bromide complexes to a-trimethylsilyl vinyl sulfones that have as a chiral auxiliary a y-mono-thioacetal moiety derived from ( + )-camphor are highly diastereoselective. A transition state that involves chelation of the organolithium reagent to the oxygen of the thioacetal moiety has been invoked. The adducts are readily converted via hydrolysis, to chiral a-substituted aldehydes22. 

The addition of a lithiated dithiane to a chiral a,/J-unsaturated sulfone has been reported, however, the stereochemical outcome and the diastereoselectivity was not addressed20. The addition of (lithiomcthylsulfonyl)benzenc to a chiral y-alkoxy-a-trimethylsilyl-aj-unsaturated sulfone gave exclusively the, vr -adduct1 2 3 4 5 7 8 9 10 11 12. 

Sulfones with a trimethylsilyl or trialkylstannyl group at the -position or at the -position are readily converted to olefins upon treatment with tetra-n-butylammonium fluoride in THF (equations 39-41). The method is compatible with the presence of a variety of functionalities. 

A similar elimination in which the tin is attacked by fluoride anions (cf. the reaction of silanes with F ) has been used179 to synthesize terminal methylene compounds as in equation (75). An analogous reaction sequence using a trimethylsilyl group in place of the trialkyltin group has been published by Hsiao and Shechter180 as part of a synthesis of substituted 1,3-butadienes. 

The use of iodotrimethylsilane for this purpose provides an effective alternative to known methods. Thus the reaction of primary and secondary methyl ethers with iodotrimethylsilane in chloroform or acetonitrile at 25—60° for 2—64 hours affords the corresponding trimethylsilyl ethers in high yield. The alcohols may be liberated from the trimethylsilyl ethers by methanolysis. The mechanism of the ether cleavage is presumed to involve initial formation of a trimethylsilyl oxonium ion which is converted to the silyl ether by nucleophilic attack of iodide at the methyl group. tert-Butyl, trityl, and benzyl ethers of primary and secondary alcohols are rapidly converted to trimethylsilyl ethers by the action of iodotrimethylsilane, probably via heterolysis of silyl oxonium ion intermediates. The cleavage of aryl methyl ethers to aryl trimethylsilyl ethers may also be effected more slowly by reaction with iodotrimethylsilane at 25—50° in chloroform or sulfolane for 12-125 hours, with iodotrimethylsilane at 100—110° in the absence of solvent, " and with iodotrimethylsilane generated in situ from iodine and trimcthylphenylsilane at 100°. ... 

It must be noted that the saturated ring system, the 1 -chloro-A -phosphirane was synthesized [84] a cyclic phospheniiun cation was postulated which is stable towards ring opening [85]. A corresponding cation could not be isolated, due to a methanid shift from a trimethylsilyl substituent. 

With the successful chemistry of the cymantrenes and the (cyclobuta-diene)tricarbonyl iron, the quest for tetraethynylated cyclobutadienes based on CpCo-stabilized complexes arose. Why would they be interesting Whereas all derivatives of 63 and 68 exhibit reasonable stability when their alkynyl substituents are protected by either an alkyl or a trimethylsilyl group, the desilylated parents are isolated only with difficulty and are much more sensitive. 

Treatment of methyl p-chlorobenzoate with an equivalent amount of commercial potassium silanolate 97 in abs. diethyl ether affords, after 4h, pure, anhydrous potassium p-chlorobenzoate in 84% yield and methoxytrimethylsilane 13 a. Trimethylsilyl trifluoroacetate reacts hkewise with sodium trimethylsilanolate 96 in THF to give sodium trifluoroacetate, in 98% yield, and hexamethyldisiloxane 7 [119] (Scheme 4.45). 

Sulfoxides containing an a-chloro group 1191 or an a-trimethylsilyl group 1193 rearrange on silylation with TMSOTf 20/triethylamine or with LDA followed by TCS 14 to the olefins 1192 and 1194 in 86 and 75% yield and HMDSO 7 [22, 23], whereas a sulfoxide with an a-cyano or a-carbomethoxy group as in 1195 reacts... 

Vinyl sulfoxides containing an a-trimethylsilyl group, for example as 1197, rearrange on heating in benzene to give the vinyl sulfoxide 1198 in up to 19% yield, the acetylene 1199 in 37% yield, and the ketene-S,0-acetal 1200 in 32% yield [25] (Scheme 8.8). 

Excess Peterson reagent 1606 a reacts with methyl benzoate, via the intermediates 1609 and 1610, to give, on work-up, some a-trimethylsilylacetophenone 1609 and 49% phenylallylsilane 1611 [15], whereas with 1606a ethyl cyclohexanecarboxylate affords only the a-trimethylsilyl-ketone 1612 [16, 17] (Scheme 10.6). 

Several ways to suppress the 2-oxonium-[3,3]-rearrangements might be envisioned. Apart from the introduction of a bulky substituent R at the aldehyde (Scheme 23) a similar steric repulsion between R and R might also be observed upon introduction of a bulky auxiliary at R. A proof-of-principle for this concept was observed upon by using of a trimethylsilyl group as substituent R in the alkyne moiety (Scheme 25, R = TMS). This improvement provided an efficient access to polysubstituted dihydropyrans via a silyl alkyne-Prins cyclization. Ab initio theoretical calculations support the proposed mechanism. Moreover, the use of enantiomerically enriched secondary homopropargylic alcohols yielded the corresponding oxa-cycles with similar enantiomeric purity [38]. 

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