Substituted trimethylsilanes, synthesis

Radical addition of dibromodifluoromethane to alkenes followed by sodium borohydride reduction is a convenient two-step method for the introduction of the difluoromethyl group.5 Either one or both carbon-bromine bonds in the intermediate dibromides may be reduced, depending on the reaction conditions. In the case of acyclic dibromodifluoromethane-alkene adducts, the reduction occurs regioselectively to yield the relatively inaccessible bromodifluoromethyl-substituted alkanes. The latter are potential building blocks for other fluorinated compounds. For example, they may be dehydrohalogenated to 1,1-difluoroalkenes an example of this methodology is illustrated in this synthesis of (3,3-difluoroallyl)trimethylsilane. 

Trialkylaryltin derivatives 30 are converted into fluoro-substituted derivatives 31. 37-38 (4-Mcth-oxyphenyl)trimethylsilane (32) in acetonitrile gives 4-fluoroanisole and (3-fluoro-4-meth-oxyphenyl)trimethylsilane in the ratio 1 2. A -Methyldiethanol esters of arylboronic acids 33 (l-aryl-5-methyl-2,8-dioxa-5-azonia-l-boranuidabicyclo[3.3.0]octanes) are converted into tluoroaromatic compounds with cesium fluoroxysulfate in acetonitrile in the presence of 1,3-dinitrobenzene at room temperature.39-40 Regiospecific synthesis of 2-fluoro-3-0-methyles-trone in 27 % yield occurs upon fluorination of the corresponding arylboronic acid with cesium fluoroxysulfate.41... 

Conversion of —Si (013)3 to —OH. Searle chemists have used this transformation in a synthesis of 4-demethoxydaunomycinone (6). Thus aryl-trimethylsilanes were known to be converted into aryl trifluoroacetates by lead tetrakistrifluoroacetate (4, 282-283) the Searle chemists found that this trifluoroacetoxylation was also applicable to benzyltrimethylsilane. With this information and knowing that 1,3-butadienes substituted by trimethylsilyl groups show selectivity in Diels-Alder reactions, they then devised the route shown in the formulation. The first step involved a Diels-Alder reaction to give 3. This product... 

The synthesis of hexamethyldisilathiane from sodium sulfide and chloro-trimethylsilane is described here. The present method is based on the convenient in situ syntheses of alkali metal selenides and diselenides. Commercial sodium sulfide or lithium sulfide are reported to be poor substitutes for in situ generated sulfides in this reaction. For example, in 1961 Abel reported that disodium sulfide reacts with chlorotrimethylsilane in pressure vessels at 250°C for 20 h to produce I. Our procedure is very convenient, utilizing readily available starting materials and apparatus under mild conditions. The yields are t3q)ically 80-88% at 0.3-mol scale. However, it can be improved to 90-95% on small scale ( 50-mmol) reactions. This procedure can be applied to the synthesis of various disilathianes. 

The synthesis of fluoroalkyl-substituted heterocycles is a subject of continuous interest this challenging issue has been presented in details in reviews [107,108]. It has been shown that trifluoromethyl carbanion, generated from (trifluoromethyl) trimethylsilane (the Ruppert reagent), adds easily to 2-chloro-3-nitropyridine. The produced o adducts can be oxidized with dimethyldioxirane (DMD) to form two isomeric 2-chloro-4-(and 6-)trifluoromethyl-3-hydroxypyridines (Scheme 30) [109]. 

In contrast to the route via the 9-methylfluorenyl-substituted sUanes 7a and 7b, no side reactions with the starting material were observed and therefore the products were formed with higher selectivity and yields. However, it was not possible to use (diphenylmethyl)trimethylsilane (14) as a precursor for the synthesis of lithiotrimethylsilane (8a), because the corresponding Si-C bond could not be cleaved under these conditions. 

Alternative Routes to Substituted (2-Phenylsulfonylethyl)-trimethylsilanes. Although the fluoride-induced elimination is a reliable and efficient method for synthesizing alkenes, the requisite silyl sulfone precursors are often better prepared by methods which avoid the use of (2). For example, eq 3 illustrates an alternative synthesis of 2,2-dialkyl-2-(phenylsulfonylethyl)trimethyl-silanes involving alkylation of a lithio sulfone with (iodomethyl)-trimethylsilane. ... 

Total syntheses of diterpenoid hydrokempenones have been accomplished by Paquette et al.,f using the Pd-catalyzed [3 + 2] cycloaddition methodology. One example is outlined on Scheme 43 and describes the synthesis of an isomeric compound 208 of 3/3-hydroxy-7/3-kemp-8(9)-en-6-one, a defense secretion agent of the neotropical species Nasutitermes octopilis. 3-AUcoxy-2-cyclohexenone 204 was efficiently functionalized and transformed to bicylic adduct 205 via a Robinson annulation reaction. Reduction of the double bond followed by condensation of dimethyl carbonate and oxidation gave the keto ester 206, which was treated with [2-(acetoxymethyl)-3-allyl]trimethylsilane, palladium acetate, and triisopropyl phosphite in refluxing tetrahydrofuran to afford a 98% yield of 207. Substituted methylenecyclopentane 207 was then functionalized by stereoselective reduction and protections, and final closure was done under basic conditions after an ozonolysis step. A modified Barton-McCombie reaction produced the desired tetracyclic adduct 208. 

Micalizio and coworker reported a three-component coupling sequence for the synthesis of substituted pyridines in 2012 [121]. The reaction proceeded through nucleophilic addition of a dithiane anion to an Q ,/3-unsaturated carbonyl followed by metallacycle-mediated union of the resulting allylic alcohol with preformed trimethylsilane-imines (generated in situ by the low temperature reaction of lithium hexamethyldi-silazide with an aldehyde) and Ag(I)- or Hg(II)-mediated ring closure. Good yields of substituted pyridines were isolated. 

Pentafluoroethylquinoline 265 was obtained by the reaction of pentafluoroethyl-trimethylsilane (254) with substituted quinoline 264 [159]. Compound 265 was a precursor for the synthesis of 266 as VRl receptor for treating pain, inflammation and other diseases (Scheme 78). 

---