Tert-butyldimethylsilyl chloride, reaction

Ketone 13 possesses the requisite structural features for an a-chelation-controlled carbonyl addition reaction.9-11 Treatment of 13 with 3-methyl-3-butenylmagnesium bromide leads, through the intermediacy of a five-membered chelate, to the formation of intermediate 12 together with a small amount of the C-12 epimer. The degree of stereoselectivity (ca. 50 1 in favor of the desired compound 12) exhibited in this substrate-stereocontrolled addition reaction is exceptional. It is instructive to note that sequential treatment of lactone 14 with 3-methyl-3-butenylmagnesium bromide and tert-butyldimethylsilyl chloride, followed by exposure of the resultant ketone to methylmagnesium bromide, produces the C-12 epimer of intermediate 12 with the same 50 1 stereoselectivity. 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

Treatment of the sulfoxide 1222 a with tert-butyldimethylsilyl chloride 85 a and excess imidazole in DMF at 25 °C furnishes the imidazole derivative 1223a in 70% yield, whereas the phenyl derivative 1222b affords, besides 47% of 1223b , the cyclized product 1224 in 24% yield and 94 a and imidazole hydrochloride [34] (Scheme 8.14). Reaction of 1225 with N-(trimethylsilyl)imidazole 1219 at 170°C affords 1226 in 50% yield [35]. 

Conversion of ketone 80 to the enol silane followed by addition of lithium aluminum hydride to the reaction mixture directly provides the allylic alcohol 81 [70]. Treatment of crude allylic alcohol 81 with tert-butyldimethylsilyl chloride followed by N-b ro m o s u cc i n i m i de furnishes the a-bromoketone 82 in 84 % yield over the two-step sequence from a.p-unsaturated ester 80. Finally, a one-pot Komblum oxidation [71] of a-bromoketone 82 is achieved by way of the nitrate ester to deliver the glyoxal 71. It is worth noting that the sequence to glyoxal 71 requires only a single chromatographic purification at the second to last step (Scheme 5.10). 

The classical Henry reaction conditions (base catalyzed addition) have some drawbacks sometimes the nitro alcohols are obtained in low yields and diastereoselectivities are not always high. To improve these results, a number of modifications were introduced. One of them is the Seebach s silyl nitronate method,25 that involves a reaction between an aldehyde with a silyl nitronate prepared by metalation of the corresponding nitro alkane with LDA, followed by reaction of the resulting nitronate with tert-butyldimethylsilyl chloride.26... 

Step [1] Protect the OH group as a tert-butyldimethylsilyl ether by reaction with tert-butyldimethylsilyl chloride and imidazole. 

TMS ethers are too labile to acid-catalysed hydrolysis to be preparatively useful, but tert-butyldimethylsilyl (TBDMS) ethers are around 10 times less susceptible to acid hydrolysis.The steric restriction about the central silicon atom presumably is the cause of the reduced reactivity, which also makes their introduction with tert-butyldimethylsilyl chloride (TBDMSCl) in pyridine selective for the primary position, but very slow. With the more basic imidazole 1 rather than 5.2 for pyridine) in DMF as base catalyst, the reaction is readier but loses its absolute selectivity for primary positions (Figure 6.25). Reaction of methyl a-o-glucopyranoside with two equivalents of TBDMS... 

A. (1R,4S)-(-)-4-tert-Butyldimethylsiloxy-2-cyclopentenyl acetate. A dry, 500-mL, three-necked, round-bottomed flask, equipped with a Teflon-coated magnetic stirring bar, rubber septum, and nitrogen inlet, is purged with nitrogen and charged with 7.67 g (54 mmol) of (1R,4S)-(+)-4-hydroxy-2-cyclopentenyl acetate (Note 1). 660 mg (5.4 mmol) of 4-dimethylaminopyridine (Note 2), 17 mL (122 mmol) of triethylamine (Note 3), and 175 mL of dichloromethane (Note 3). The reaction mixture is cooled to 0°C in an ice-water bath, and tert-butyldimethylsilyl chloride (10.24 g, 68 mmol) (Note 2) is introduced in one portion. The ice-water bath is removed and the mixture is allowed to warm to room temperature and stir for 3 hr. At this point, more silyl chloride is added if necessary (Note 4). After 5 hr, 200 mL of water is added, the mixture is transferred to a separatory funnel and the organic phase separated. The aqueous phase is extracted with three 100-mt portions of dichoromethane. The combined... 

The OH group was protected by reaction with tert-butyldimethylsilyl chloride (TBDMS) in order to obtain the living anionic polymerisation. Diphenylethylene (DPE) was used to lower the living chain reactivity. The monomers were added in order styrene, styrene-o-TBDMS, DPE, MMA to the solvent tetrahydrofuran (THF) at 78°C in nitrogen with stirring. The reaction was terminated with methanol and precipitated by hexane to give the product PS-b-poly(styrene-o-TBDMS)-b-PMMA which was dried in vacuum at 130°C then... 

CAL and AK lipase were used in these reactions and the results are listed in Table 6.19. In one case, the acetylated product 151 was converted (after protection of the alcohol with tert-butyldimethylsilyl chloride) to a phosphine oxide with vinylmagnesium bromide, with clean inversion at the phosphorus atom. 

N-Carboxy anhydrides 1201 of several a-amino acids, including jS-chloro-L-alanine, can be formed by reaction of an N-tert-butoxycarbonyl (Boc) amino acid (1199) with tert-butyldimethylsilyl chloride and subsequent treatment of the resulting silyl ester 1200 with oxalyl chloride in the presence of dimethylformamide [821],... 

Typical procedure. N-Carboxy-ji-cMoro-L-alanme anhydride [821] To a solution of N-Boc-yS-chloro-L-alanine (400 mg, 1.8 mmol) and tert-butyldimethylsilyl chloride (283 mg, 1.9 mmol) in ethyl acetate (2 mL) at 0 °C was added triethylamine (244 pL, 1.8 mmol). Triethylamine hydrochloride was immediately precipitated, and after stirring for 30 min at 0 °C, it was filtered off (244 mg, 100%). The filtrate was then concentrated in vacuo to leave an oil, which was redissolved in dichloromethane (3.0 mL). After chilling to 0 °C, oxalyl chloride (195 pL, 2.25 mmol) was added, followed by 2-3 drops of DMF. Once gas evolution had subsided (approximately 2 min), additional DMF (2 drops) was added and the reaction mixture was allowed to warm to room temperature. Further DMF was added dropwise until no further gas was evolved (approximately 10 min). The solution was then diluted with THF (ca. 10 mL) and concentrated once more. This routine ensures removal of any unreacted oxalyl chloride. The flask containing the resulting oil was placed on a vacuum line, and evaporation of the DMF (over about 2 h) afforded white needles. Recrystallization from CH2Cl2/hexane gave the desired NCA in quantitative yield (270 mg). 

The synthetic technique is summarized in Scheme 3. Reaction of chaparrin (41b) with tert-butyldimethylsilyl chloride 11) afforded the crystalline disilyl derivative (93). The latter was obtained in better yield by silylation of (41b) with tert-butyldimethylsilyl enol ether of pentane-2,4-dione 105). The hydroxyl function at C-1 of (93) was effectively protected using trimethylsilyl triflate to afford the trisilyl lactone (94) which upon treatment with lithium diisopropylamide (LDA) and subsequent exposure to MoOs-pyridine-HMPA (M0O5PH) 104) gave the required 15-hydroxy lactone (95). Treatment of the latter with isovaleryl chloride afforded the crystalline ester (96) which was selectively desilylated to (97). Oxidation of the free allylic hydroxyl and complete desilylation of the resulting disilyl enone with tetrabutylammonium fluoride (BU4NF) afforded the natural cytotoxic quassinoid castelanone (34). 

Saxena et al. (2003) have carried out the reactions of alcohols or phenols with tert-butyldimethylsilyl chloride (TBDMSCl) or trimethylsilyl chloride (TMSCl) in presence of catalytic amount (20 mol%) of iodine in a microwave oven for 2 min, which resulted into corresponding silyl ethers in excellent yield. It was also observed that under similar reaction conditions, iodine in methanol deprotects the silyl ether into its parent alcohol or phenol. 

The 0-silylation reaction of alcohols is important as a protection method of hydroxyl groups. 0-Silylations of liquid or crystalline alcohols with liquid or crystalline silyl chlorides were found to be possible in the solid state. For example, when a mixture of powdered L-menthol (26), ferf-butyldimethylsilyl chloride (27), and imidazole (28) was kept at 60 °C for 5 h, 0-tert-butyldi-methylsilyl L-menthol (29) was obtained in 97% yield [8] (Scheme 4). Similar treatments of 26 with the liquid silyl chlorides, trimethyl- (30a) and triethylsilyl chloride (30b), gave the corresponding 0-silylation products 31a (89%) and 31b (89%), respectively, in the yields indicated [8] (Scheme 4). However, 0-silylation of triisopropyl- (30c) and triphenylsilyl chloride (30d) proceeded with difficultly even at 120 °C and gave 31c (57%) and 31d (70%), respectively, in relatively low yields. Nevertheless, when the solvent-free silylation reactions at 120 °C were carried out using two equivalents of 30c and 30d, 31c (77%) and 31d (99%) were obtained, respectively, in relatively high yields. 

The tris(trimethylsilyl)silyl ligands can be easily modified by reactions with silyl chlorides, as shown with a series of phenylated species Mes Ph SiCl (n = 0-3). Furthermore, triisopropyl, thexyldimethylsilyl, or tert-butyldimethylsilyl substitution are all easily possible.190 The crystallographic characterization of some of the alkali metal derivatives indicates a direct correlation between ligand size and resulting structural parameters. 

The steric bulk which accounts for the relative stability of tert-butyldimethylsilyl ethers also hinders their formation and so the reaction between tot-butyldimethylsilyl chloride and hydroxy groups in the presence of pyridine is very slow. In the presence of catalytic amounts of imidazole, however, the reaction proceeds rapidly and in high yield as shown in Equation Si2.3. 

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