T-Butyldimethylsilyl chloride

Reduction of the ester group to give secondary alcohol 54 and sub sequent protection with /e/t-butyldimethylsilyl chloride leads to si-lyl ether 55 Oxidative cleavage of the cyclopropyl ring in this system proceeds through a radical mechanism and results in ben/oate ester 56. Basic ester hydrolysis gives piimar> alcohol 16... 

The t-butyldimethylsilyl ether (TMBS-ether), formed from the alcohol with t-butyldimethylsilyl chloride in the presence of imidazole in dimethylformamide solution,84 is more stable to hydrolysis than the TMS-ether (see also Section 4.2.66, p. 461). Deprotection is readily effected by treatment with 2-3 equivalents of tetrabutylammonium fluoride in tetrahydrofuran at 25 °C,84a or tetrabutyl-ammonium chloride and potassium fluoride dihydrate in acetonitrile.84b... 

To a solution of 350 mg of methyl 4-[2-endo-hydroxy-l-exo-hydroxymethyl-3a,8b-cis-2,3,3a,8b-tetrahydro-lH-5-cyclopenta[b]benzofranyl]butyrate in 3.5 ml of anhydrous dimethylformamide cooled in an ice bath were added 140 mg of imidazole and 360 mg of t-butyldimethylsilyl chloride, and after the mixture was stirred for 3 hours at room temperature, dimethylformamide was removed under reduced pressure. The residue was dissolved in a mixture of 10 ml of acetic anhydride and 5 ml of pyridine. After the mixture was stirred for 2 hours at room temperature, the reaction mixture was concentrated. 

Methanesulfonyl chloride Diethylaluminium chloride Orpholinopropanesulfonic acid buffer Benzyl-a-bromopropionate trans-l-(p-Nitrobenzyloxycarbonyl)-4-hydroxy-L-proline Methanesulfonyl chloride t-Butyldimethylsilyl chloride... 

Reagents i, mesitoyl chloride ii, 03 iii, isopropenylMgBr iv, Ac20-py v, Bu"Li-isopropyl-cyclohexylamine-THF, -78°C vi, HMPA-t-butyldimethylsilyl chloride-THF vii, hydrolysis viii, LiAlH4. 

Yagi and coworkers84 reported the preparation of ce-keto acylsilanes in a one-pot operation. To a mixture of dibromomethane and tc/t-butyldimethylsilyl chloride in THF, LDA was added at — 78 °C, forming /< /7-bu tyldi methyl silyldibromomcthy (lithium, 89. To the resulting mixture 4-methoxybenzonitrile was added. Quenching with 1 M HC1 afforded a-keto acylsilane, 90, in 55% yield (Scheme 30). 

It has been observed that reactions of dibutylstannylene acetals of terminal 1,3-diols, or polyols having primary hydroxyl groups free, with t-butyldimethylsilyl chloride yield primary silyl ethers, even for such compounds as methyl a-D-mannopyranoside, where the expectation (see Table VI) for most reactions is for substitution to occur on a secondary oxygen atom.85 88 These observations probably arise from a very large kinetic preference for reaction with primary oxygen atoms, that is, ki2 and k]2 > k2 and K22, in Fig. 12, rather than a rearrangement from initially formed secondary silyl ethers. 

The Step 3 product (0.217 mol), t-butyldimethylsilyl chloride (0.282 mol), imidazole (0.563 mol), and 140ml of DME were mixed and heated for lOhours at 50°C. The mixture was then poured into water and extracted with CH2CI2. It was dried and concentrated, and the residue was purified by flash column chromatography with hexane/EtOAc, 3 1, respectively, and the product was isolated in 87% yield. 

The product from Step 1 (33 mmol) was dissolved in 50 ml THE containing NEtj (66 mmol), cooled in an ice bath, and t-butyldimethylsilyl chloride (43 mmol) dissolved in 15 ml THE added dropwise. The cooled reaction mixture was stirred 5 hours then stored in a refrigerator 64 hours. The cooled mixture was poured into ice- cold water, extracted with EtOAc, and the extract washed with brine and dried. The residue was purified by chromatography using EtOAc/hexane, 1 9, and the product isolated in 79% yield. 

Bergaptol (50 mmol) was dissolved in 100 ml DMF containing imidazole (73.4 mmol) and t-butyldimethylsilyl chloride (72.8 mmol), stirred at ambient temperature 4 hours, then quenched with 500 ml EtOAc. The organic phase was washed 8 times with 100 ml brine, mixed with n-heptane, concentrated, and a yellow solid isolated. The solid was washed 3 times with 100ml heptane and the product isolated in 82% yield. H- and C-NMR data supplied. 

Both (1) and (2) convert alcohols, even tertiary ones, into the corresponding silyl ethers in the presence of pyridine without formation of alkenes the reaction is more rapid than that with t-butyldimethylsilyl chloride. The ethers derived from 2 are unusually stable they are not cleaved by CsF in DMSO even at elevated temperatures. But they can be cleaved by BF3 etherate in CH2CI2 at 0° to give borate ethers, which can be hydrolyzed by NaHC03 at 0°. 

One of the newest silylation agents, t-butyldimethylsilyl chloride (TBMSCl), offers no particular advantage in base silylation. However, be-... 

In combination wifh t-butyldimethylsilyl chloride, InClj catalyzes the aldol reaction between aldehydes and t-butyldimethylsilyl enol ethers in anhydrous organic solvents [140]. It has recently been found that the InCh-catalyzed Mukaiyama aldol reaction proceeds in water (Tab. 8.26) [141]. The reaction proceeds cleanly under almost neutral conditions to give /1-hydroxy ketones. The aqueous phase with IriClj can be reused. Water-soluble aldehydes such as glyoxylic acid and a commercial formaldehyde solution can be used directly for these reactions. 

Ketene silyl acetals. The enolsilylation of esters is highly dependent on the bases used. Contrasting stereoselectivities in the silylation of methyl a-f-butyldi-methylsiloxyacetate are found with respect to the reaction conditions The ( )-isomer is obtained in the trimethylsilylation promoted by lithium tetramethylpiperidide, and the (Z)-isomer from the reaction with t-butyldimethylsilyl chloride in the presence of LHMDS and HMPA. 

The initial research efforts focused on the preparation of the precursor, the omegar-r-butyldimethylsilyloxyalkyl halide, from the corresponding haloalcohol and /-butyldimethylsilyl chloride. The t-butyldimethylsilyl moiety was originally introduced as an alcohol protecting group by Corey. In this procedure, 1.2 equivalents of t-butyldimethylsilyl chloride and 2.5 equivalents of imidazole, as the acid acceptor, were utilized. The solvent employed was N,N-dimethylformamide. These reaction conditions afforded the desired product in excellent yield. However, the cost of the excess reagents, their subsequent removal, the utilization of an expensive, hydroscopic solvent, and an aqueous workup were not very practical from a commercial perspective. Since its inception in 1972, a variety of other procedures have been described for the preparation of t-butyldimethylsilyl ethers. These procedures typically require solvents that are expensive, difficult to recycle, or environmentally unfriendly. Furthermore, traces of some of these solvents, such as methylene chloride, in the precursor would be incompatible with lithium metal in the subsequent lithiation step. 

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