Silyl Ether - Selective Deprotection

Selective Deprotection

Selective deprotection of silyl groups is possible in many instances. For example:

Silyl ethers are mainly differentiated on the basis of sterics or electronics. In general, acidic deprotections deprotect less hindered silyl groups faster, with the steric bulk on silicon being more significant than the steric bulk on oxygen. Fluoride-based deprotections deprotect electron-poor silyl groups faster than electron-rich silyl groups. There is some evidence that some silyl deprotections proceed via hypervalent silicon species.

The selective deprotection of silyl ethers has been extensively reviewed. Although selective deprotections have been achieved under many different conditions, some procedures, outlined below, are more reliable. A selective deprotection will likely be successful if there is a substantial difference in sterics (e.g., primary TBS vs. secondary TBS or primary TES vs primary TBS) or electronics (e.g. primary TBDPS vs. primary TBS). Unfortunately, some optimization is inevitably required and it is often necessary to run deprotections partway and recycle material.

Some Common Acidic Conditions:

• 100 mol% 10-CSA (camphorsulfonic acid) in MeOH, room temperature; a "blast" of acid, deprotects primary TBS groups within ten minutes.
• 10 mol% 10-CSA, 1:1 MeOH:DCM, −20 or 0 °C; deprotects a primary TBS group within two hours at 0; if CSA is replaced by PPTS, the rate is approximately ten times slower; with pTsOH, approximately ten times faster; solvent mixture is crucial.
• 4:1:1 v/v/v AcOH:THF:water, room temp.; this is very slow, but can be very selective.

Some Common Basic Conditions:

• HF-pyridine, 10:1 THF:pyridine, 0 °C; an excellent deprotection; removes primary TBS groups within eight hours; reactions using HF must be run in plastic containers.
• TBAF, THF or 1:1 TBAF/AcOH, THF; TBDPS and TBS groups can be deprotected in the presence of one another under different conditions.