Enantioselective Synthesis of 3‐Fluorochromanes via Iodine(I)/Iodine(III) Catalysis. Issue 35 (9th June 2020)

• Record Type: Journal Article
• Authors: Sarie, Jérôme C.; Thiehoff, Christian; Neufeld, Jessica; Daniliuc, Constantin G.; Gilmour, Ryan
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 35(2020)
• Page Start: 15069
• Page End: 15075
• Publication Date: 2020-06-09
• Subjects: chromanes -- fluorine -- gauche effect -- organocatalysis -- stereospecificity; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202005181
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 ArIF2 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 IIinv pathway. Abstract : An iodine(I)/iodine(III) catalysis strategy to access enantioenriched 3‐fluorochromanes is disclosed (up to 7:93 e.r .). In situ generation of ArIF2 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 IIinv pathway.