A deprotection procedure using SO₃H silica gel to remove non-silyl protecting groups

Abstract

Protecting groups are indispensable in organic synthesis and there is a great need for a variety of deprotection methods. Here, we investigated the scope of the application of a deprotection procedure using SO₃H silica gel, which we have previously reported as a desilylation procedure. Under these conditions, -OMOM, -OSEM, -OTHP, and -OAc groups and dimethyl acetal were cleaved. Pivaloyloxy, benzyloxy and methoxy carbonyl groups remained intact and selective deprotection of TBS groups in the presence of other protecting groups was accomplished. We succeeded in cleaving an acetyl group on a secondary alcohol in a highly polar nortropine derivative. Our findings here provide another deprotection option and would be helpful in the synthesis of multifunctional compounds.

Graphical Abstract

Keywords:

• SO₃H silica gel
• solid-supported catalyst
• acid-catalyzed deprotection

Acknowledgments

We are grateful to Dr. Kenichiro Nagai (Analytical Unit for Organic Chemistry of Kitasato University) for help with the structure determination of the newly synthesized compounds.

Notes

1 This dimer may be produced through the elimination of the protonated alkoxide moiety and the subsequent addition of the deprotected alcohol to the resulting oxonium cation (see Scheme 1). Methanol used in these reaction was not dehydrated grade and contained several amounts of water. It is possible that this water hydrolyzed the oxonium cation intermediate and suppressed the formation of the dimers.

2 By adding methanol solutions of the substrates to SO₃H silica gel, we obtained fluffy powder of silica gel. Then the powder was heated at the indicated temperatures. Thus the reactions could be performed above the boiling points of the solvents.

3 SO₃H silica gel is produced by modifying the surface of silica gel using a trimethoxy-type silane coupling agent. The residual methoxy group may cause the conversion.

4 The cLogP value was calculated using ChemDraw Professional version 16.0.