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.
Wong, J. Y. F., Lewandowska, A., Trowse, B., & Barker, G. (2019). Lithiation Substitution of Unprotected Benzyltetrazoles. Organic Letters, 21(17), 7069-7072. https://doi.org/10.1021/acs.orglett.9b02633