SCHEDULED MAINTENANCE
Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles†
Filipe
Vilela 
ab
and
Graeme
Barker
*ab
ab
and
Graeme
Barker
*ab
Abstract
Tetrazoles play a prominent role in medicinal chemistry due to their role as carboxylate bioisosteres but have largely been overlooked as C–H functionalisation substrates. We herein report the development of a high-yielding and general procedure for the heterobenzylic C–H functionalisation of 5-alkyltetrazoles in up to 97% yield under batch conditions using a metalation/electrophilic trapping strategy. Through the use of thermal imaging to identify potentially unsafe exotherms, a continuous flow procedure using a flash chemistry strategy has also been developed, allowing products to be accessed in up to 95% yield. This enabled an extremely high productivity rate of 141 g h−1 to be achieved on an entry-level flow system.
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