TBAF

(Tetra-n-butylammonium Fluoride)

General Information:

Structure:

CAS Number: 87749-50-6 (trihydrate)

Molecular Weight: 261.46 g/mol (anhydrous basis)

315.51 (trihydrate)

TBAF is a quaternary salt that is used as a source of fluorine. The fluorine anion is typically used for deprotection of silyl ether groups or as a mild base. The good solubility of TBAF in organic solvents makes it a useful alternative to poorly soluble inorganic bases. Reactions involving TBAF are typically carried out at temperatures below 100 C due to its low thermal stability.

TBAF is typically obtained as a trihydrate (TBAF-3H2O), 1M solution in THF, or 75 wt% solution in H2O. TBAF will always contain some water due to the fact that the fluorine ion is such a great hydrogen bond acceptor.

Common Uses:

Reagent for the SEM deprotection

Procedure excerpt:

To a stirred solution of the SM (250 mg, 0.43 mmol) in THF (4 mL) was added TBAF (4 mL, 1M in THF). The reaction mixture was stirred at 80 C for 12 h. After cooling . . .

[full procedure]

Reagent for TBS deprotection

Procedure excerpt:

A mixture of the SM (319 mg, 0.848 mmol) and TBAF (221 mg, 0.848 mmol) in THF (20 mL) was stirred at RT overnight. Upon completion, the resulting solution was . . .

[full procedure]

Reagent in substitution reactions with TMSCN

Procedure excerpt:

A solution of the SM (80.0 g, 286 mmol) and TMSCN (28.2 g, 286 mmol) in ACN (600 mL) was stirred at RT for 30 min. The mixture was cooled to 0 C and treated with TBAF . . .

[full procedure]

Reagent in SNAr reactions with TMSCN

Procedure excerpt:

A mixture of the SM (150 mg, 0.36 mmol), TBAF (281 mg, 1.08 mmol), TMSCN (107 mg, 1.08 mmol) in DMF (3 mL) was stirred at 100 C for 1 h. After cooling . . .

[full procedure]

Safety:

TBAF is very hygroscopic. Contact of TBAF with acid liberates toxic gas.

References:

1) Patent Reference: WO2015140133, page 103, (11.7 MB)

2) Patent Reference: WO2014152144, page 59, (4.6 MB)

3) Patent Reference: WO2016014463, page 101, (6.7 MB)

4) Patent Reference: WO2016011390, page 151, (20.2 MB)

5) Wikipedia: Tetra-n-butylammonium fluoride (link)

6) www.sigmaaldrich.com: Tetrabutylammonium fluoride solution (link)

7) Pearson, A. J.; Roush, W. R.; Handbook of Reagents for Organic Synthesis, Activating Agents and Protecting Groups