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TCI Practical Example: Regioselective Silylation of an Unprotected Carbohydrate Using the Boronic Acid and the Phosphine Oxide

We are proud to present the selective tert-butyldiphenylsilylation of the 3-position hydroxy group of methyl α-L-fucopyranoside by using the co-catalyst system of 4-(dimethylamino)phenylboronic acid and tributylphosphine oxide.

Used Chemicals

• 4-(Dimethylamino)phenylboronic Acid [D4428]
• Tributylphosphine Oxide [T0921]
• tert-Butyldiphenylchlorosilane (= TBDPSCl) [B1223]
• Methyl α-L-Fucopyranoside [M1051]
• N,N-Diisopropylethylamine (= DIPEA) [D1599]
• Acetonitrile

Procedure

To a solution of methyl α-L-fucopyranoside (356 mg, 2 mmol), 4-(dimethylamino)phenylboronic acid (66 mg, 0.4 mmol, 0.2 eq.), tributylphosphine oxide (87 mg, 0.2 mmol, 0.2 eq.) and DIPEA (517 mg, 0.68 mL, 4.0 mmol, 2.0 eq.) in acetonitrile (10 mL) was added TBDPSCl (1.10 g, 4.0 mmol, 2.0 eq.) at rt and the mixture was stirred at 60 °C. After 24 h, methanol (1 mL) was added to the reaction mixture and the solvent was removed under reduced pressure. The residue was purified by column chromatography (ethyl acetate:hexane = 0:1 - 1:1 on silica gel) to give 1 as a colorless oil (510 mg, 61% yield).

Experimenter’s Comments

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:1, Rf = 0.59).

Analytical Data

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 7.75-7.67 (m, 4H), 7.48-7.36 (m, 6H), 4.68 (d, 1H, J = 3.2 Hz), 3.93-3.80 (m, 2H), 3.68 (brq, 1H, J = 6.5 Hz), 3.44-3.43 (m, 1H), 3.29 (s, 3H), 2.55 (brs, 1H), 1.53 (d, 1H, J = 8.9 Hz), 1.22 (d, 3H, J = 6.8 Hz), 1.10 (s, 9H).

Lead Reference

• Regioselective silylation of pyranosides using a boronic acid / Lewis base co-catalyst system
• • D. Lee, M. S. Taylor, Org. Biomol. Chem. 2013, 11, 5409.