Difluorination of α-(bromomethyl)styrenes via I(I)/I(III) catalysis: facile access to electrophilic linchpins for drug discovery. Issue 17 (31st March 2021)

• Record Type: Journal Article
• Authors: Häfliger, Joel; Livingstone, Keith; Daniliuc, Constantin G.; Gilmour, Ryan
• Is Part Of: Chemical science. Volume 12:Issue 17(2021)
• Page Start: 6148
• Page End: 6152
• Publication Date: 2021-03-31
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc01132d
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Simple α-(bromomethyl)styrenes can be processed to a variety of 1, 1-difluorinated electrophilic building blocks via I(I)/I(III) catalysis. Abstract : Simple α-(bromomethyl)styrenes can be processed to a variety of 1, 1-difluorinated electrophilic building blocks via I(I)/I(III) catalysis. This inexpensive main group catalysis strategy employs p -TolI as an effective organocatalyst when combined with Selectfluor® and simple amine·HF complexes. Modulating Brønsted acidity enables simultaneous geminal and vicinal difluorination to occur, thereby providing a platform to generate multiply fluorinated scaffolds for further downstream derivatization. The method facilitates access to a tetrafluorinated API candidate for the treatment of amyotrophic lateral sclerosis. Preliminary validation of an enantioselective process is disclosed to access α-phenyl-β-difluoro-γ-bromo/chloro esters.