Photoredox Catalysis for the Synthesis of N-CF2 H Compounds Using 1-((N-(difluoromethyl)-4-methylphenyl)-sulfonamido)pyridin-1-ium Trifluoromethanesulfonate

Daniel Lin; Juan Pablo de Los Rios; G K Surya Prakash

doi:10.1002/anie.202304294

Photoredox Catalysis for the Synthesis of N-CF₂ H Compounds Using 1-((N-(difluoromethyl)-4-methylphenyl)-sulfonamido)pyridin-1-ium Trifluoromethanesulfonate

Angew Chem Int Ed Engl. 2023 Jul 24;62(30):e202304294. doi: 10.1002/anie.202304294. Epub 2023 Jun 19.

Authors

Daniel Lin¹, Juan Pablo de Los Rios¹, G K Surya Prakash¹

Affiliation

¹ Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, 837 Bloom Walk, 90089-1661, Los Angeles, CA, USA.

PMID: 37235718
DOI: 10.1002/anie.202304294

Abstract

N-(difluoromethyl)amino (-NCF₂ H) compounds are of great interest given their unique and underexplored physiochemical properties. The lack of structural diversity in NCF₂ H compounds is likely due in part to the shortage of protocols for efficient installation. Presented herein is a new shelf-stable pyridinium reagent that enables the direct installation of the N-(difluoromethyl)sulfonamide moiety [N(Ts)CF₂ H)] onto (hetero)arenes and alkenes for the diversification of aryl and alkyl NCF₂ H compounds. The described protocol utilizes blue light photoredox catalysis and displays broad functional group tolerance with excellent chemoselectivity. Additional transformations and applicability towards a photoredox continuous flow protocol are also demonstrated.

Keywords: Difluoromethylamines; Flow Chemistry; Photoredox Catalysis; Pyridinium; Radicals.

Grants and funding

Loker Hydrocarbon Research Institute, University of Southern California