Tetrazole Derivatives. III. Tetrazole Acid Derivatives

Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles

“…13 Examples of C-H functionalisation of tetrazole 5-substituents are much rarer. 14 Flippin has reported ortho-lithiation of 5phenyltetrazoles, 15 and an early example of lithiation-substitution of N-methyl-5-alkyltetrazoles at the α-position was reported by Thomas et al, 16 however pyrophoric t-BuLi and cryogenic temperatures were required and methods for N-methyl deprotections have yet to be identified, precluding the products from use as carboxylate bioisosteres. Later, a more convenient lithiation-substitution of trityl protected tetrazoles using n-BuLi was reported by Huff et al (scheme 1).…”