Ethers, triisopropylsilyl removal

The TES group is the most labile of the common silyl protecting groups, apart from TMS, and can usually be removed in the presence of TBS, triisopropylsilyl (TIPS) and rerf-butyldiphenylsijyl (TBDPS) groups. Selective deprotection of a TES ether using aqueous trifluoroaoetic acid left two TBS ethers and two TIPS ethers intact in the Merck synthesis of the immunosuppressant FK-506 [Scheme 4.19].22 Weaker acids such as H2O-HOAC-THF (3 5 11) at room temperature,33 HF pyridine24 and pyridinium p-toluenesulfonate [Scheme 4.2Q]23 can accomplish similar transformations. 

Triisopropylsilyl ethers are generally cleaved under the same conditions as those used for TBS ethers (i.e.T TBAF-THF, HF-acetonitrile, or HF-pyridine-THK see above) but longer reaction times are frequently necessary consequently, TBS ethers can be removed selectively in many cases. Nevertheless, in a synthesis of Mycotrienol, a secondary TIPS ether was cleaved efficiently and rapidly with p-toluenesulfonic acid in methanol without detriment to a nearby second-... 

A 0.010-0.016 M solution of the dibromoolefin in hexanes under nitrogen was cooled to —78°C, and 1.1-1.2 eq. n-BuLi per dibromoolefin moiety was slowly added over a period of 2 min. Reactions were allowed to warm to —10 to —5°C over a period of 30-60 min. The reaction was quenched with 10 mL aqueous NH4CI at about —5" C. Diethyl ether was added (20 mL), the organic layer was separated, and washed with aqueous NH4CI solution (2 X 20 mL), and dried over MgS04. The solvent was removed in vacuo to give 70% 1,12-bis(triisopropylsilyl)-l,3,5,7,9,ll-dodecahexayne, m.p. 78-80°C, Rf = 0.87 (hexanes). 

Protection of Hydroxyl Groups. Triisopropylsilyl chloride (TIPSCl) continues to be widely used as the means of introducing the TIPS protecting groups onto alcohols. The steric bulk of the three isopropyl groups on the silicon atom provides considerable stability under acidic and basic conditions and allows selective removal of smaller, more labile silyl groups in the presence of TIPS ethers.i2.i3... 

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