Synthesis and Physicochemical Properties of 2-SF5-(Aza)Indoles, a New Family of SF5 Heterocycles

Abstract

Structural diversity in heterocyclic chemistry is key to unlock new properties and modes of action. In this regard, heterocycles embedding emerging fluorinated substituents hold great promises. Herein is described a strategy to access 2-SF5- (aza)indoles for the first time. The sequence relies on the radical addition of SF5Cl to the alkynyl p-system of 2-ethynyl anilines followed by a cyclization reaction. A telescoped sequence is proposed making this strategy very appealing and reproducible on gram scale. Downstream functionalizations are also demonstrated, allowing an easy diversification of N- and C3-positions. Ames test, pKa, logP and DSC measurements of several fluorinated 2-Rfindoles are also disclosed. These studies highlight the strategic advantages that a C2-pentafluorosulfanylated motif impart to a privileged scaffold such as indole.