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

Tetrazole is a motif of several marketed drugs and is an important substructure for the discovery of new drug candidates. This motivates the development of convenient methods for the synthesis of tetrazole derivatives.

Researchers at the Organic Synthesis Methodology Group (Latvian Institute of Organic Synthesis) have reported direct functionalization of tetrazole by C–H deprotonation with the turbo Grignard reagent providing a metalated intermediate with increased stability. The metalated intermediate can be used for the reaction with a range of electrophiles such as aldehydes, ketones, Weinreb amides, and iodine.

The research is published in the Journal of Organic Chemistry (IF= 4.35) and it is the first example of the application of the turbo Grignard for the deprotonation of tetrazoles.