Synthesis of 1,2,4-Trimethoxybenzene and Its Selective Functionalization at C-3 by Directed Metalation

Abstract

A new and efficient strategy was developed for the preparation of 1,2,4-trimethoxybenzene (3, a powerful attractant of Euglossini bees) and its C-3 derivatives (7a–j), from vanillin (2) in 56% overall yield.

Keywords:

• Aromatic lithiation
• directed metalation
• Euglossini bees
• regioselectivity
• 1,2,4-trimethoxybenzene

ACKNOWLEDGMENTS

We thank CAPES, CNPQ, FAPERJ, and FUJB for financial support and also Qiang Wang, a Postdoctoral student in Clayton H. Heathcock's research group, Department of Chemistry, University of California Berkeley, USA, for personal contributions.

Notes

∗There were employed 1,1,eq of the organolithium reagent and CH₃I.

∗∗Time of the reaction before the addition of the electrophile.