Technical Library


The 2-(tert-butyldiphenylsilyl)ethyl, TBDPSE, group has been shown to be an excellent protecting group for phenols. The protection of several phenols was carried out in excellent yields with none of the direct O-Si derivative being formed, as is the case with other silylethanol protecting groups (Eq. 83).105 The group has been shown to be stable to a variety of reaction conditions. Strong acid or fluoride serves for the deprotection step.

Trimethylsilylethanol was reacted with triphosgene to generate trimethylsilylethylchloroformate (Teoc-Cl) ‘in-situ’ and this was used to convert N-benzylpiperidines to N-Teoc protected piperidines (Eq. 84).106

The direct conversion of aryl fluorides to aryloxyethylsilyl ethers using trimethylsilylethanol has been reported. This interesting formation of a silyl-protected alcohol results in the conversion of an aryl fluoride to a phenol (Eq. 85).107 The conversion occurs in modest to excellent yield with only electronic deficient aryl fluorides able to undergo the reaction. The aromatic rings must be electron poor for a successful conversion. It is interesting to note that the substitution reaction occurs in favor of the Peterson elimination to form trimethylsilanol and ethylene.

The catalyst 19 was employed in the enantioselective protection of one of the two prochiral hydroxyl groups. The presence of the 2-hydroxyl group proved necessary for success. This was used in an enantioselective synthesis of cleroindicin F 2 and cleroindicine C 3 (Eqs. 86 & 87).108

Reminiscent of a Brook rearrangement the observation of an oxygen to oxygen silyl migration under the proper conditions is noted. An example of the migration of a TBS group from a secondary oxygen to a primary oxygen is shown in Eq. 88.109

A fluorous version of TBAF, 20, has been reported. This presents a potential solution to the issue of removing the TBAF after a deprotection step has been carried out. It has been shown to be selective in the removal of TES ethers in the presence of TBS ethers.110

Silver fluoride has been found to selectively desilylate ethynyltriisopropylsilanes in the presence of several other functional moieties.111 The direct conversion of THP ethers to silyl ethers is possible via the reaction with the silyl triflate (Eqs. 89 & 90).112 This is possible with protected 1,3-diols derivatives and with PMB-protected alcohols as well (Eq. 91). The conversion of PMB ethers to silyl ethers has also been accomplished with the silyl triflate and triethylamine (Eq. 92).113

Silyl ethers were converted to arylalkyl ethers via fluoride ion desilylation substitution. The alkyl halide must be a reactive one. Direct esterification of the silyl ether is also possible under similar conditions (Eq. 93).114

In an interesting twist on the use of an organosilane for protection of diols, Larson and Hernández found that the enol trimethylsilyl ether of acetone very effectively provided acetonides from diols. As an extension of this it was found that enol trimethylsilyl ethers are excellent reagents for the formation of the corresponding even the acetonide of trans-1,2-cyclohexanediol (Eq. 94 & 95).115 The corresponding reactions were also shown to occur with 2-mercaptoethanol and enol trimethylsilyl ethers.

The fluorescent organosilane 21 represents a silicon-based protecting group that has the capability of serving as a fluorescent tag as well.116

The organosilanes 22, 23, and 24 represent potential chiral silicon-based protecting groups. The intriguing pentafluorophenylsilane 25 , known as the flophemesyl chloride, is used as a derivatizing agent for electron-capture detection and photoionization detection.117,118