Chlorotrimethylsilane reagent

Oltra and Cuerva have reported a unified strategy for the synthesis of the eudesmanolides that relies on the collidine-chlorotrimethylsilane reagent... 

The manganese dioxide/chlorotrimethylsilane reagent system gives a cleaner, trans-stereoselective chlorination of unconjugated alkenes in high yield136. This increased selectivity towards addition has been taken as evidence of negligible involvement of free chlorine atoms and a non-radical-chain mechanism has been proposed. 

Trimethylsilyl trifluoromethanesulfonate (trimethylsilyl triflate) is the most synthetically useful representative of the family of trialkylsilyl perfluoroalkane-sulfonates (for a review, see reference 101) This reagent is commercially available or can be prepared easily by the reaction of chlorotrimethylsilane and triflic acid [101] It has wide application in organic synthesis as an excellent silylating reagent... 

In addition to the boron trifluoride-diethyl ether complex, chlorotrimcthylsilanc also shows a rate accelerating effect on cuprate addition reactions this effect emerges only if tetrahydrofuran is used as the reaction solvent. No significant difference in rate and diastereoselectivity is observed in diethyl ether as reaction solvent when addition of the cuprate, prepared from butyllithium and copper(I) bromide-dimethylsulfide complex, is performed in the presence or absence of chlorotrimethylsilane17. If, however, the reaction is performed in tetrahydrofuran, the reaction rate is accelerated in the presence of chlorotrimethylsilane and the diastereofacial selectivity increases to a ratio of 88 12 17. In contrast to the reaction in diethyl ether, the O-silylated product is predominantly formed in tetrahydrofuran. The alcohol product is only formed to a low extent and showed a diastereomeric ratio of 55 45, which is similar to the result obtained in the absence of chlorotrimethylsilane. This discrepancy indicates that the selective pathway leading to the O-silylated product is totally different and several times faster than the unselective pathway" which leads to the unsilylated alcohol adduct. A slight further increase in the Cram selectivity was achieved when 18-crown-6 was used in order to increase the steric bulk of the reagent. 

The reversal of the stereoselectivity is attributed to the ability of chlorotrimethylsilane to trap the initially formed cuprate-enone complex, thereby suppressing equilibration of the diastereomeric complexes. The copper-catalyzed 1,4-addition of Grignard reagents to 5-substituted 2-cyclo-hexenone also proceeded with very high trans diastereoselectivity22. 

The structurally simplest silicon reagent that has been used to reduce sulphoxides is the carbene analog, dimethylsilylene (Me2Si )29. This molecule was used as a mechanistic probe and did not appear to be useful synthetically. Other silanes that have been used to reduce sulphoxides include iodotrimethylsilane, which is selective but unstable, and chlorotrimethylsilane in the presence of sodium iodide, which is easy to use, but is unselective since it cleaves esters, lactones and ethers it also converts alcohols into iodides. To circumvent these complications, Olah30 has developed the use of methyltrichlorosilane, again in the presence of sodium iodide, in dry acetonitrile (equation 8). A standard range of sulphoxides was reduced under mild conditions, with yields between 80 and 95% and with a simple workup process. The mechanism for the reaction is probably very similar to that given in equation (6), if the tricoordinate boron atoms in this reaction scheme are replaced... 

Hexamethyldisiloxane is available from Aldrich Chemical Company, Inc. The reagent may also be prepared by the procedure described in the following paragraph. The submitters have used chlorotrimethylsilane purchased from Aldrich Chemical Company, Inc., and Silar Laboratories, Inc. (10 Alplaus Road, Scotia, New York 12302) either as supplied or after distillation from calcium hydride. No appreciable difference in yield was noted between preparations using undistilled and distilled reagent. 

Chlorotrimethylsilane is available from Aldrich Chemical ( ompany, Inc. The reagent was distilled before use. 

Reagents. n-butyl lithium (Koch-Light) was supplied as a solution in n-hexane (1.55 mol dm-J) and transferred to the reaction vessel via a suba-seal cap using a syringe. Chlorotrimethylsilane and trichloromethylsilane (Aldrich) were distilled under reduced pressure. Ammonia (BDH) was supplied as an "0.880" solution in water. 

RCu(CN)ZnI.u These new copper reagents are prepared by reaction of primary or secondary iodides with zinc that has been activated with 1,2-dibromoethane and chlorotrimethylsilane. The resulting organozinc compounds are then allowed to react with the THF-soluble CuCN-2LiCl (equation I). Because of the mild conditions, these new reagents can be prepared from iodides containing keto, ester, and nitrile groups. 

Alkylzinc iodides These reagents are prepared by reaction of alkyl iodides with Zn/Cu in toluene-N,N-dimethylacetamide (DMA). In the presence of 1 equiv. of chlorotrimethylsilane they can add to aldehydes to form alcohols. DMA may be replaced as the cosolvent by N-methylpyrrolidone (NMP), but HMPT retards this reaction. This reaction can be used to obtain y-, 8-, and e-hydroxy esters from P-, y-, and 8-zinc esters (equation I). 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

In the cyclic series several examples, as summarized above, have been provided. The diastereoselectivity, l or u, essentially can be controlled by the choice of the halide in the Grignard reagent and the additive, i.e., employing either organomagnesium bromide with copper(I) bromide and a phosphine, or organomagnesium chloride with copper(I) bromide and chlorotrimethylsilane (see also syn/anti selectivity in Section 1.1.1.2.). 

To 2.05 g (10.0 mmol) of (-)-(4S, 5S )-4.5-dihydro-4-methoxymelhyl-2-mcthyl-5-phenyloxazole in 35 mL of 1,2-dimethoxyethane (N, — 78 X) are added dropwise 4.55 mL (10.5 mmol) of butyllithium (2.3 M in hexane) to produce a light yellow solution that is stirred ail additional. 30 min. Then 2.5 g (57 mmol) of oxirane are added ileat, in a stream, via a cannula from the septum-topped reagent bottle. The clear solution is slowly warmed from —78 to 0 C over a 6-h period. After the mixture is cooled back down to — 78 X, 1.4 mL (11 mmol) of chlorotrimethylsilane aTe added neat and the solution is allowed to warm to r.t. Most of the solvent is then removed on a rotary evaporator, the residue is taken up in hexane, and the insoluble matter is filtered off. Concentration and distillation gives the product as a clear oil yield 2.5 g (80%) bp 150 C/0.015 Torr [a]23 -41.6 (c = 9.8, c HCI3). 

In a typical procedure, 10 mg of a sugar is dissolved in 1 ml of pyridine, treated successively with 0.2 ml of hexamethyldisilazane and 0.1 ml of chlorotrimethylsilane, and the mixture shaken for a few seconds. Reaction is normally complete within 5 minutes. This treatment corresponds to the original procedure used by Sweeley and colleagues,5 and is the method used in the great majority of cases. Apart from the deliberate use of other trimethylsilylating reagents, most of the variations on this fundamental reaction have been designed to meet certain special conditions. 

N,0-Bis(trimethylsilyl)acetamide (3) is an alternative trimethylsilylating reagent that has been found to trimethylsilylate L-ascorbic acid completely,139 and to react with tertiary hydroxyl groups in steroids.140,141 The latter observation is of interest, in view of the isolation from antibiotic substances of branched-chain carbohydrates possessing tertiary hydroxyl groups.142 Some authors have recommended that the highly reactive bis(trimethylsilyl)acetamide (3) be used in the absence of pyridine, in preference to a mixture of hexamethyldisilazane and chlorotrimethylsilane in this solvent.143 In the tri-... 

Solvents that have been less extensively used are N-methyl-2-pyrrolidinone and hexamethylphosphoric triamide.183 The author of this article183 also discussed the purification of chlorotrimethylsilane, and the anomalous results that may be obtained from the use of impure reagent have been commented on in the case of analyses of pentaerythritol.184 The various methods available for the bulk purification of methyl sulfoxide have been reviewed,185 and a symposium on this compound reviewed its use as a solvent in selected reactions.186... 

A Grignard reagent (r)6-CaH5MgI)Cr(CO)3 gave only an 8% yield of (Tj6-CaH5SiMe3)Cr(CO)3 with chlorotrimethylsilane (82). 

The conj ugate addition of lithium dimethylcuprate and other organoeopper reagents to a,/ -unsaturated ketones is a reaction which has had wide application and which has been fairly well studied.6 In order that the positional specificity which has been conferred upon the enolate anions generated by such additions might be maintained, these intermediates have been intercepted with acetic anhydride,6 chlorotrimethylsilane, and diethyl phosphorochloridate.4 8... 

Preparation1 This reagent can be prepared in 66% yield by reaction of triflic acid with isopropenyltrimethylsilane, CH2=C(CH3)Si(CH3)3, which is available from Petrarch or which can be prepared by a Wurtz-Fittig reaction of 2-chloro-propene with sodium and chlorotrimethylsilane in ether/HMPT. 

The combinations of chlorotrimethylsilane-hexamethylphosphoramide (HMPA) or chlorotrimethylsi-lane-4-(dimethylamino)pyridine (DMAP) are also powerful accelerants for copper(I)-catalyzed Grignard conjugate additions,33 and stoichiometric organocopper and homocuprate additions (Scheme 21 ).36 However, these reactions must be performed in tetrahydrofuran instead of ether.37 These procedures are noted for their high yields with stoichiometric quantities of Grignard reagents, excellent chemoselectivity and efficiency with a,3-unsaturated amides and esters and enals.58 Typically, additions to enals proceed via the S-trans conformers to afford stereo-defined silyl enol ethers for example, enals (122) and (124) give the ( )-silyl enol ether (123) and (Z)-silyl enol ether (125), respectively. 

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