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Enantioselective Synthesis of 3‐Fluorochromanes via Iodine(I)/Iodine(III) Catalysis
Author(s) -
Sarie Jérôme C.,
Thiehoff Christian,
Neufeld Jessica,
Daniliuc Constantin G.,
Gilmour Ryan
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202005181
Subject(s) - enantioselective synthesis , iodine , catalysis , chemistry , stereospecificity , stereochemistry , combinatorial chemistry , molecule , small molecule , plenum space , organic chemistry , biochemistry , physics , thermodynamics
The chromane nucleus is common to a plenum of bioactive small molecules where it is frequently oxidized at position 3. Motivated by the importance of this position in conferring efficacy, and the prominence of bioisosterism in drug discovery, an iodine(I)/iodine(III) catalysis strategy to access enantioenriched 3‐fluorochromanes is disclosed (up to 7:93 e.r .). In situ generation of ArIF 2 enables the direct fluorocyclization of allyl phenyl ethers to generate novel scaffolds that manifest the stereoelectronic gauche effect. Mechanistic interrogation using deuterated probes confirms a stereospecific process consistent with a type II inv pathway.