Trimethylsilyl formate

Cyanation of aldehydes and ketones is an important chemical process for C C bond formation." " Trimethylsilyl cyanide and/or HCN are commonly used as cyanide sources. The intrinsic toxicity and instability of these reagents are problematic in their applications. Acetyl cyanide and cyanoformates were used as cyanide sources in the enantioselective cyanation of aldehydes catalyzed by a chiral Ti complex and Lewis base (Scheme 5.31)." The Lewis base was necessary for the good yields and selectivities of these reactions. The desired products were obtained in the presence of 10mol% triethyl amine and 5mol% chiral titanium catalyst (Figure 5.14). Various aliphatic and aromatic aldehydes could be used in these reactions. 

Cycloaddition Cyanogen azide. Ethyl azidoformate. Tetracyanoethylene (cyclobutane formation). Trimethylsilyl azide. 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Conversion to acetates, trifluoroacetates (178), butyl boronates (179) trimethylsilyl derivatives, or cycHc acetals offers a means both for identifying individual compounds and for separating mixtures of polyols, chiefly by gas—Hquid chromatography (glc). Thus, sorbitol in bakery products is converted to the hexaacetate, separated, and determined by glc using a flame ionisation detector (180) aqueous solutions of sorbitol and mannitol are similarly separated and determined (181). Sorbitol may be identified by formation of its monobensylidene derivative (182) and mannitol by conversion to its hexaacetate (183). 

Trimethylsilyl)ethoxymethyl Ether (SEMOR) Me3SiCH2CH20CH20R Formation... 

Me3SiCH2CH=CH2i TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thiophenol except when CF3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-/-butyldi-methylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. 

Trimethylsilyl) ethyl Carbonate (TMSEC) Me3SiCH2CH20C02R Formation... 

N,N - Bis(trimethylsilyl)sulfur(rV) diimide Me3SiN=S=NSiMc3 is an especially versatile source of the N=S=N functionality in the formation of both acyclic and cyclic S-N compounds. It is conveniently prepared by the reaction of NaN(SiMc3)2 and thionyl chloride (Eq. 2.5). 

N3S3F2][MF6] can be isolated from the reaction of 8.12b with MF5 (M = As, Sb), but they decompose to give the bicyclic cation [S4N5] (Section 5.3.8). Treatment of 8.12a with trimethylsilyl azide generates the polymer presumably via the intermediate formation of... 

Sisyl Ether [Tris(trimethylsilyl)silyl Ether] [(CH3)3Si]3SiOR Formation... 

O-Trimethylsilyl-5-alkyl Acetals and Ketals R2C(SR )OSiMe3 Formation... 

Trimethylsilyl)ethyl (TMSE) Ester RC02CH2CH2Si(CH3)3 Formation... 

The Boekelheide reaction has found utility in other synthetic methodology. An approach to 2,3-pyridynes made use of this chemistry in the preparation of the key intermediate 30. Treatment of 28 with acetic anhydride produced the desired pyridone 29. Lithiation was followed by trapping with trimethylsilyl chloride and exposure to triflic anhydride gave the pyridyne precursor 30. Fluoride initiated the cascade of reactions that resulted in the formation of 2,3-pyridyne 31 that could be trapped with appropriate dienes in Diels-Alder reactions. 

Use of bis(trimethylsilyl)acetamide and bis(trimethylsilyl)urea for protection and as control reagents in reactions with formation of heterocycles 98S357. 

Treatment of an epimeric mixture of 4-substituted 2-(trimethylsilyloxy)-5-phenyl-3-phenylthio-l,4-oxazine 264 with ZnBr2 led to the stereoselective formation of perhydropyrido[2,l-c][l,4]oxazine 266 via the iminium ion 265 by the phenyl bearing stereocenter directed addition of the olefinic double bond from the /S-face of the cyclic moiety (97SL799, 98T10309). Similarly, an epimeric mixture of (45,9aS)-l-trimethylsilyloxy-4-phenyl-3,4,6,7-tetra-hydropyrido[2,l-c][l,4]oxazine was prepared by cyclization of (Z)-5(S)-phenyl-3-phenvlsulfanyl-2-trimethylsilyloxy-4-[4-(trimethylsilyl)but-3-enyll morpholine (OOSC2565). 

With the use of trimethylsilyl-substituted starting materials after Denmark et al., the disadvantageous formation of a mixture of isomers can be avoided. The vinyl silane derivatives react by loss of the TMS group in the last step ... 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

With the exocyclic alkylidene at C-13 properly in place, the elaboration of the l,5-diyn-3-ene moiety can now be addressed. Cleavage of both acetate and trimethylsilyl functions in 86 with basic methanol, followed by triethylsilylation of the newly formed tertiary hydroxyl group, efficiently affords alkyne 25 (86 % overall yield). This substance was regarded as a viable candidate for a Pd-catalyzed coupling reaction.12 Indeed, treatment of 25 with (Z)-chloroenyne 26 in the presence of a catalytic amount of Pd(PPh3)4 and Cu1 results in the formation of enediyne 24 in 91 % yield. 

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