2021-01- Synthesis and Physico-Chemical Properties of 2-SF5-(Aza)Indoles, A New Family of SF5-Heterocycles

Debrauwer, V.; Leito, I.; Lõkov, M.; Tshepelevitsh, S.; Parmentier, M.; Blanchard, N.; Bizet, V. ACS Org. Inorg. Au, 2021, DOI:10.1021/acsorginorgau.1c00010.

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 π-system of 2-ethynyl anilines followed by a cyclization reaction. A telescoped sequence is proposed making this strategy veryappealing 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-Rf-indoles are also disclosed. These studies highlight the strategic advantages that a C2- pentafluorosulfanylated motif impart to a privileged scaffold such as indole.

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