Chlorotrimethylsilane reaction with amines

The function of the tertiary amine is to catalyze the reaction by forming some of the more nucleophilic alkoxide ion and to neutralize the HCl formed during the reaction. Tertiary amines are not nucleophilic because the three attached allgroups provide steric hindrance. Tertiary amines can react with protons and act as a base but will not react with electrophiles such as chlorotrimethylsilane. 

Disilathianes, for example (SiH3)2S and [(CH3)3Si] 2S, have been prepared by several routes, namely, the reaction of iodosilane with silver8 and mercuric2 sulfides halosilanes with lithium sulfide,7 [NH4]SH,9 and [Me3NH]SH7 disilaselenane with H2S10 and trisilylphosphine with sulfur.10 Recently, the synthesis of hexamethyldisilathiane, [(CH3)3Si] 2S, was described from the protolysis of l-(trimethylsilyl)imidazole with H2S and from the dehydrohalogen-ation of chlorotrimethylsilane and H2S with a tertiary amine.11 Both of these methods require about 18 hours. 

The MgX2/R3N systems offer another useful synthetic interest. Recently, Evans and coworkers have demonstrated that substoichiometric amounts of magnesium halides in the presence of an amine and chlorotrimethylsilane catalyze the direct aldol reaction of A-acyloxazolidinones and A-acylthiazolidininethiones with high diastereoselectivity (equation 59). 

Bisftrimethylsilyl) peroxide, [(CH3)3SiO]2 (1). Mol. wt. 168.37, b.p. 42730 mm., reasonably stable to heat, soluble in aprotic organic solvents. The peroxide is obtained most conveniently by reaction of chlorotrimethylsilane with the 1 2 complex of H 202 with DABCO.1 This complex, m.p. 112° (dec.), is readily obtained by reaction of the amine with 30% H202 and serves as a reasonably stable source of anhydrous H202.2... 

The main deficiencies with the preceding approaches are that only arylene-amines give good yields (and there are other routes to 5-arylimidazolcs), and since unsubstituted vinylamines (R = H Scheme 4.3.3) are not available this means that 4- and 5-unsubstituted imidazoles are not accessible. An alternative route involving silyl enol ethers (6) has been reported to overcome these deficiencies (Scheme 4.3.4). Silyl enol ethers can be made either by treating a ketone with chlorotrimethylsilane and triethylamine in DMF solution, or by sequential reactions of the ketone with LDA and chlorotrimethylsilane in 1,2-dimethoxyethane. This normally gives a mixture in which the less highly substituted enol ether is the major product (enolate formation is kinetically controlled) [25], When (6) is heated with an At-chloroamidine for 12-24h in chloroform solution in the presence of an equimolar amount of dry pyridine 1,2-disubstituted (5) (R = H) or 1,2,5-trisubstituted (5) imidazoles are... 

Many (a-hydroxyalkyl)cyclopropanes have been converted to the corresponding (a-chloroal-kyl)cyclopropanes. Most reactions have been performed with thionyl chloride in the presence of an amine or HMPA, or absence - ° of an amine, but hydrogen chloride, mesyl chloride, hexachloroacetone/triphenylphos-phane, carbon tetrachloride/triphenylphosphane, chlorotrimethylsilane, " carbon tetrachloride/hexamethylphosphoric triamide and A-chlorosuccinimide have also been used. The yields are generally satisfactory to good, in some cases even excellent. Thus, methyl... 

The pioneering studies in this area were reported in 1999 by Narasaka, who demonstrated intramolecular heteroatom Heck-type reactions of 0-pentafluorobenzoyl oximes [97]. As shown below, treatment of unsaturated substrate 97 with a catalytic amount of Pd(PPh,y in the presence of triethyl amine provided pyrrole 98 upon workup with chlorotrimethylsilane. The mechanism of this reaction proceeds via oxidative addition of the N—O bond to afford 99, which undergoes alkene insertion into the Pd—N bond to provide alkyl-palladium complex 100. The exo-methylene product 101 is generated by [i-hydride elimination from 100, and isomerization to the desired pyrrole 98 occurs when chlorotrimethylsilane is added. 

Trimethylsilylation has been accomplished with a large number of reagents most of which are commercially available. The cheapest (chlorotrimethylsilane) and the most reactive (trimethylsilyl triflate) rapidly silylate hydroxyl groups in the presence of a suitable base such as pyridine, triethylamine, i-Pr2NEt, imidazole, or DBU but an aqueous workup is required to ensure complete removal of the resultant amine hydrochloride or triflate whence hydrolysis of the nascent TMS ether may occur. In some cases the insoluble salt may be removed by filtration without aqueous workup. A wide range of solvents can be used for the reaction such as dichloromethane, acetonitrile, THF, or DMF. Care must be taken with trimethylsilyl triflate (TMSOTf) since it will convert aldehydes and ketones to the corresponding enol silanes and it will open epoxides in a reaction that has preparative significance [Scheme 4.6]. Similar transformations can be accomplished with tert-butyldimelhylsilyl triflate (TBSOTf) or triethylsilyl triflate (TESOTf). ... 

Nitriles are, with few exceptions, not reduced by NaBHa. SulfuratedNaBHa, prepared by the reaction of sodium borohydride with sulfur in THF, is somewhat more reactive than NaBHa, and reduces aromatic nitriles (but not aliphatic ones) to amines in refluxing THF. Further activation has been realized by using the Cobalt Boride system, (NaBHa-CoCD which appears to be one of the best methods for the reduction of nitriles to primary amines. More recently it has been found that Zirconium(IV) Chloride Et2SeBr2, CuSOa, Chlorotrimethylsilane, and l2 are also efficient activators for this transformation. The NaBHa-Et2SeBr2 reagent allows the selective reduction of nitriles in the presence of esters or nitro groups, which are readily reduced by NaBHa-CoCL. 

Preparative Methods can be prepared by the reaction of diethyl-amine with chlorotrimethylsilane, hexamethyldisilazane, or cyanotrimethylsilane. ... 

Nitrogen Silylation Reactions. lV-(Trimethylsilyl)imidazole can serve as an electrophilic trap for the highly reactive intermediate formed in the reaction of A -aryl imines with trifluo-romethyltrimethylsilane under fluoride catalysis (eq 15). In the absence of lV-(trimethylsilyl)imidazole, the reactive intermediate decomposes to difluorocarbene, shifting the equilibrium toward the starting imine derivative. Chlorotrimethylsilane or fV-methyl-IV-trimethylsilylacetamide were not able to promote the formation of monotrifluoromethylated amine, with the former leading to almost complete recovery of the starting trifluoromethyltrimethyl-silane while the latter induced decomposition of the imine. 

Polymeric amines can be proton acceptors, acyl transfer agents, or ligands for metal ions. The 2- and 4-isomers of poly(vinylpyridine) (11) and (12) and the weakly basic ion exchange resins, p-dimethylaminomethylated PS (2) and poly(2-dimethylaminoethyl acrylate), are commercial. The ion exchange resins are catalysts for aldol condensations, Knoevenagel condensations, Perkin reactions, cyanohydrin formation and redistributions of chlorosilanes. " The poly(vinylpyridine)s have been used in stoichiometric amounts for preparation of esters from acid chlorides and alcohols, and for preparation of trimethylsilyl ethers and trimethylsilylamines from chlorotrimethylsilane and alcohols or amines. Polymer-suppored DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (52) in stoichiometric amounts promotes dehydrohalogenation of alkyl bromides and esterification of carboxylic acids with alkyl halides. The protonated tertiary amine resins are converted to free base form by treatment with aqueous sodium hydroxide. 

Other Reactions. Treatment of an active hydroxy compound with 2,2 -dipyridyl disulfide and n-BuyP yields the corresponding thiopyridyl derivative. This methodology has been applied to the preparation of 5-arylthio-5 -deoxyribonucleosides (eq 8). Monophosphate esters [R0P(0)(0H)2] will react similarly to form the activated triphenylphosphonium adduct, which, in the absence of an added external nucleophile, dimerizes yielding a pyrophosphate. A-Methylimidazole has been found to catalyze this transformation. The addition of alcohols or amines, however, traps the phosphoryloxyphosphonium salt as the mixed diphosphate ester or mixed ester/amide, respectively (eq 9). Chlorotrimethylsilane and (pyS)2 have also been reported to facilitate the oxidation of phosphites to phosphates. ... 

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