Triethylsilyl group groups, silyl ethers

Silyl ethers, such as TMS, triethylsilyl (TES), triisopropylsilyl (TIPS), lerl-butyldi-methylsilyl (TBS), and terl-butyldiphenylsilyl (TBDPS) ethers (Scheme 2.6), are frequently used in carbohydrate chemistry due to their unique reactivity and steric effect (see Section 2.4.1) [1, 2], These groups are typically introduced onto the molecule by treatment with the corresponding silyl halide or triflate (OTf) and a base, such as Et3N, pyridine, 2,6-lutidine, or imidazole. 

Another common method for alcohol protection is reaction with RjSiCl to give a silyl ether. Reaction conditions usually involve RjSiCl, with 4-dimethylaminopyridine (DMAP) as the base. Both the ease of preparation of the silyl ether and the stability of the protected species depend on the nature of the R groups. Trimethylsilyl ethers (ROTMS) are very labile and readily removed with water and dilute acid. The triethylsilyl group (ROTES) is a little more robust but may be removed with fluoride ion (the use of fluoride to cleave silyl groups reflects the strength of the Si-F bond). r-BuMejSiCl (TBDMSCl) reacts selectively with... 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

In addition, trimethylsilyl ether 197a and triethylsilyl ether 197b have conformations different from those of compounds 198a and 198b247, which bear a bulky PhsSi or a (z -Pr) vSi group, respectively. The change of conformation is due to the steric hindrance from these two bulky silyl groups. 

The final step in a recent synthesis of the antifungal agent Papulacandin D involved deprotection of five O-silyl groups including a di-ferr-butylsilylene group, a triethylsilyl ether and two phenolic tri-isopropylsilyl ethers [Scheme 3.115],215 Acid conditions were precluded by the add lability of the side chain. Use of TBAF was complicated by problems in separating the product from tetrabuty-Lammonium salts. The desired global deprotection was accomplished with tris-(dime thy iamino)sulfoni urn difluorotrimethylsilicate (TAS-F). 

The triethylsilyl ether 147 thus formed regiospecifically from the diol 150 [Rl=(BnO)2 (0), R2=Bn], which was optically resolved by a chiral column chromatography, was transformed to Ins(2,4,5)P3 and Ins(l,4,5)P3 (Schema 3-23). At this stage, temporary protection of OH-1 with the silyl group is not necessary, i.e. 150 can be directly phosphorylated by the phosphite-phosphonium approach as described in the section on phosphorylation (Scheme 2-6). H The diol 150 was used furthermore as a versatile synthetic intermediate for the synthesis of myo-inositol 1,2-cyclic-4,5-trisphosphate 152 (Scheme 3-23), 8 2-acyl analogues of Ins(1,4,5)P3, and inositol phospholipid. 

Trimethylsilylation has been accomplished with a large number of reagents most of which are commercially available. The cheapest (chlorotrimethylsilane) and the most reactive (trimethylsilyl triflate) rapidly silylate hydroxyl groups in the presence of a suitable base such as pyridine, triethylamine, i-Pr2NEt, imidazole, or DBU but an aqueous workup is required to ensure complete removal of the resultant amine hydrochloride or triflate whence hydrolysis of the nascent TMS ether may occur. In some cases the insoluble salt may be removed by filtration without aqueous workup. A wide range of solvents can be used for the reaction such as dichloromethane, acetonitrile, THF, or DMF. Care must be taken with trimethylsilyl triflate (TMSOTf) since it will convert aldehydes and ketones to the corresponding enol silanes and it will open epoxides in a reaction that has preparative significance [Scheme 4.6]. Similar transformations can be accomplished with tert-butyldimelhylsilyl triflate (TBSOTf) or triethylsilyl triflate (TESOTf). ... 

---