Flash chemistry enables high productivity metalation-substitution of 5-alkyltetrazoles.
Chem Sci
; 12(40): 13413-13424, 2021 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-34777760
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Chem Sci
Ano de publicação:
2021
Tipo de documento:
Article