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Updated: Jan 20, 2026

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
Lithiation Substitution of Unprotected Benzyltetrazoles
Jeff Y F Wong1, Agnieszka Lewandowska1, Benjamin R Trowse1
1Institute of Chemical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, U.K.
Abstract:
1H-Tetrazoles occupy an important role in modern medicinal chemistry, but few methods for their modification exist. Many extant protocols require the use of a difficult to remove N-alkyl-protecting group, precluding the products from use as carboxylate bioisosteres, the major role of tetrazoles in pharmaceuticals. We herein report a convenient, protecting-group-free lithiation-substitution protocol for benzylic tetrazoles. Metalation with n-BuLi at 0 °C followed by electrophilic trapping gave a range of α-functionalized benzyltetrazoles in up to 91% yield.
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