Hexafluoroisobutylation of enolates through a tandem elimination/allylic shift/hydrofluorination reaction.

ABSTRACT: The isobutyl side chain is a highly prevalent hydrophobic group in drugs, and it notably constitutes the side chain of leucine. Its replacement by a hexafluorinated version containing two CF₃ groups may endow the target compound with new and advantageous properties, yet this modification remains overlooked due to the absence of a general and practical synthetic methodology. Herein, we report the first general method to introduce the hexafluoroisobutyl group into ketoesters, malonates, 1,3-diketones, Schiff base esters and malononitrile. We demonstrated that the reaction occurs through an elimination/allylic shift/hydrofluorination cascade process which efficiently overcomes the usual fluoride β-elimination observed with α-CF₃-vinyl groups. We showed that with alkali m

SUBMITTER: Delamare A 

PROVIDER: S-EPMC9400614 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature