The use of organosilane reagents for the protection of alcohols is a widely used strategy in organic chemistry when enhanced product selectivity is needed. Their ubiquitous use in the organic synthesis literature, despite the addition of two extra steps to the overall reaction sequence, speaks for their effectiveness. These protections are typically carried out by heating a mixture of the organic chlorosilane (R3SiCl) with the alcohol in the presence of a weak base (i.e. triethylamine). A variety of organosilyl protecting groups have been used, namely tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBS or TBDMS), triphenylsilyl (TPS), dimethylphenylsilyl (DMPS), triisopropylsilyl (TIPS or TIPPS), trimethylsilyl (TMS). While the smaller organosilyl groups, such as TMS, can be easily deprotected under acidic conditions, the larger organosilyls are more resistant to acids and thus removed via other conditions.[1] One of the most common reagents for removing bulky silyl groups is tetrabutylammonium fluoride (TBAF) due to its effectiveness, and high solubility. If solubility isn’t a concern, KF, CsF, or NH4F also do the job.
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If deprotected product isn’t soluble in water, excess TBAF can easily be removed via aqueous wash. Product is extracted with a less polar organic solvent.
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TBAF can pose problems when the resulting alcohol is only soluble in polar solvents because removal of excess reagent and other tetrabutylammonium byproducts becomes challenging. For such cases, a nice Organic Syntheses procedure describes removal of these salts with commercially available DOWEX 50WX8 resin and CaCO3.[2]
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Removal of byproduct organic fluorosilanes after TBAF reaction is typically done by column chromatography. However, if product isn’t volatile, byproduct can be removed in high vacuum. If you know of ways to avoid the column, comment below
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For more delicate organosilyl group removals, a comprehensive list of conditions can be found in the Gelest website:
Deprotection of Silyl Ethers - Gelest
[1] Crouch, R. D. Selective deprotection of silyl ethers. Tetrahedron 2013, 69, 2383-2414.
[2] McDermott, L.; Witkowski, D. C.; Garg, N. K. A Convenient Method for the Removal of Tetrabutylammonium Salts from Desilylation Reactions. Org. Synth. 2022, 99, 53-67.