Tert-Butyldimethylsilyl chloride

Fig. 4. Synthesis of monensin from homochiial natural products TBS = tert-butyldimethylsilyl chloride.

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... 

Butyllithium and tert-butyldimethylsilyl chloride were obtained from Fluka Chemie AG and used as received. 

Dimethylaminopyridine and tert-butyldimethylsilyl chloride were purchased from the Aldrich Chemical Company, Inc., and used without purification. 

Triethylamine (8) Ethanamine, N,N-diethyl- (9) (121-44-8) tert-Butyldimethylsilyl chloride CORROSIVE, TOXIC Silane, chloro(1,1-dimethyl-ethyljdimethyl- (9) (18162-48-6)... 

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

The TBDMS ethers are prepared with tert-butyldimethylsilyl chloride and imidazole in tetrahydrofuran. The usual reagent for cleavage of this type of sUyl ether is also tetra-butylammonium fluoride another mild and efficient method for the deprotection is the use of iodine in methanol.P ... 

C6H15CISi tert-butyldimethylsilyl chloride 18162-48-6 21.25 0.8837 2 9508 C7H3CIF3N02 4-chloro-3-nitrobenzotrifluoride 121-17-5 20.00 1.7706 2... 

C6H1402S2 3,6-dithi aoctane-1,8-diol 5244-34-8 498.15 43.706 2 9165 C6H15CISI tert-butyldimethylsilyl chloride 18162-48-6 398.05 34.182 1.2... 

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... 

Podophyllotoxin (11) was used as the starting material, and it was silylated with tert-butyldimethylsilyl chloride (TBDMSCl) in the presence of imidazole in dimethylformamide at 75°C (ref. 28). The resulting product was purified by silica gel column chromatography (CHCl, EtOAc = 10 1) to give podophyllotoxin-TBD-MS form (26) (2,3-trans) and picropodophyllin-TBDMS form (27) (2,3-cis) which isomerized at the C-3 position in a ratio of 5.2 1. 

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