Tert-Butyldimethylsilyl ether TBDMS

A slight modification of Corey synthesis (see Scheme 3.16) affords an estrane that bears a hydroxyl at C14. The 14-dehydroestrone intermediate from that synthesis is first reduced to give the corresponding 17[3-hydroxy analogue. This, in turn, is converted to its tert-butyldimethylsilyl ether (TBDMS) (32-1) by reaction with the silyl chloride (Scheme 3.32). Oxidation by means of w-chloroperbenzoic acid (mCPBA) affords the 14—15 epoxide 32-2 as a 3 1 mixture of a- and p-epimers. Treatment of the former with lithium aluminum hydride leads to the alcohol... 

A method to prepare 1,2-amino alcohols through the dihydroxylation of an enol ether has been reported by Merck (Scheme 3.25) [330]. The ee was reported to diminish if shorter chain alcohols were used although the TBDMS enol ether was used successfully in a structurally related system [331]. Indeed, early work by Sharpless with acyclic methyl and tert-butyldimethylsilyl ethers showed high en-antioselectivities in AD reactions (cf. Table 3.2) [332]. 

The tert-butyldimethylsilyl (TBDMS) protection of 50 gave a silyl ether... 

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 ... 

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... 

Theil et al. developed a method for chemoenzymatic synthesis of both enantiomers of cispentacin [89]. frans-2-Hydroxymethylcyclopentanol, obtained by the sodium borohydride reduction of ethyl 2-oxocyclopentanecarboxylate, was monosilylated with tert-butyldimethylsilyl (TBDMS) chloride to afford 55. Lipase PS-catalysed transesterification with vinyl acetate in /erf-butyl methyl ether furnished the ester 56 and the alcohol 57. The deacetylated 58 was obtained by the Mitsunobu reaction with phthalimide, triphenylphosphine and diethyl azodicarboxylate (DEAD) to furnish the cis oriented 59 with inversion of configuration (not retention as mentioned in the original article) (Scheme 9). Desilylation, Jones oxidation and subsequent deprotection with aqueous methylamine gave the ( R,2S) enantiomer 5 [89]. The (15, 2/f) enantiomer was prepared by the same route from the silyl alcohol 57. 

Removal of the methoxymethyl groups from 43 with HCl, followed by protection of the secondary amine with benzyl chloroformate afforded the carbamate 9. Selective silylation of the 4-hydroxy group of 9 by treatment with 1.2 equiv of tert-butyldimethylsilyl chloride and 2.4 equiv of imidazole in DMF at room temperature for 1 h afforded the corresponding silyl ether as a single isomer in 80% yield that was subjected to acetylation at the C-3 hydroxyl group to afford the carbamate 11, which upon removal of the Cbz and TBDMS groups furnished 1. 

For some applications, and particularly for GC-MS (see also Chapter 14), there are advantages to using tert-butyldimethylsilyl (TBDMS) esters, and these are made from up to 5 mg of the acid(s) in 100 yl of dimethyl-formamide containing 20 /imol of imidazole and 10 /imol of TBDMCS. The reaction mixture is heated at 60 °C for 15 minutes, an equal volume of 5% NaCl is added and the esters are extracted into 1 ml of ether for analysis by GC or GC-MS [108]. An improved reagent for making TBDMS esters is N-TBDMS-N-methyltrifluoro-acetamide, or MTBSTFA, used much as in 2.5.1 above. For most acids room temperature is probably sufficient for complete esterification in 5-15 minutes yields are good and the derivatives are stable [109]. 

A procedure for the efbcient preparation of enol-TBDMS ethers for the GC—MS analysis of steroids and bile acids is described in Section 4.4.3 [12], Significantly, tert-butyldimethylsilylation of hydroxyl groups in the 1) ,... 

The selective cleavage of the iV-t-butoxycarbonyl group in the presence of TBDMS (t-butyldimethylsilyl) (selective only when the protected alcohol was phenolic) or TBDPS (tert-butyldiphenylsilyl) (completely selective) ethers can be achieved using a saturated solution of HCl in ethyl acetate. 

---