Open AccessSynthesis and Physicochemical Properties of 2-SF5-(Aza)Indoles, a New Family of SF5 Heterocycles
Author(s) -
Michaël Parmentier,
Vincent Debrauwer,
Ivo Leito,
Märt Lõkov,
Sofja Tshepelevitsh,
Nicolas Blanchard,
Vincent Bizet
Publication year - 2021
Publication title -
acs organic and inorganic au
Language(s) - English
Resource type - Journals
ISSN - 2694-247X
DOI - 10.1021/acsorginorgau.1c00010
Subject(s) - combinatorial chemistry , chemistry , indole test , stereochemistry , nanotechnology , materials science
Structural diversity in heterocyclic chemistry is key to unlocking new properties and modes of action. In this regard, heterocycles embedding emerging fluorinated substituents hold great promise. Herein is described a strategy to access 2-SF 5 -(aza)indoles for the first time. The sequence relies on the radical addition of SF 5 Cl to the alkynyl π-system of 2-ethynyl anilines followed by a cyclization reaction. A telescoped sequence is proposed, making this strategy very appealing and reproducible on a gram scale. Downstream functionalizations are also demonstrated, allowing an easy diversification of N- and C3-positions. Ames test, p K a , log P , and differential scanning calorimetry 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 an indole.