Functionalization of 1N-Protected Tetrazoles by Deprotonation with the Turbo Grignard Reagent.

1N-PMB-protected tetrazole undergoes C-H deprotonation with the turbo Grignard reagent, providing a metalated intermediate with increased stability. This can be used for the reaction with electrophiles such as aldehydes, ketones, Weinreb amides, and iodine. C-H deprotonation with the turbo Grignard reagent is compatible with the PMB-protecting group at the tetrazole, which can be cleaved using oxidative hydrogenolysis and acidic conditions. The method enables the tetrazole functionalization at the fifth position by overcoming the difficulties associated with retro [2 + 3] cycloaddition of the metalated intermediates.