Flash Chemistry Enables High Productivity Metalation-Substitution of 5-Alkyltetrazoles

Yuk Fung Wong, Christopher Thomson, Filipe Vilela, Graeme Barker

Research output: Contribution to journalArticlepeer-review

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 to be achieved on an entry-level flow system.
Original languageEnglish
JournalChemical Science
Early online date15 Sep 2021
DOIs
Publication statusE-pub ahead of print - 15 Sep 2021

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Chemistry(all)
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Flash Chemistry Enables High Productivity Metalation-Substitution of 5-Alkyltetrazoles'. Together they form a unique fingerprint.

Cite this