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

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.

SUBMITTER: Wong JYF

PROVIDER: S-EPMC8528014 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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

Wong Jeff Y F JYF Thomson Christopher G CG Vilela Filipe F Barker Graeme G

Chemical science 20210915 40

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 ...[more]

PMID: 34777760

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