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Organophotoredox-Driven Three-Component Synthesis of β-Trifluoromethyl β-Amino Ketones

Marta Gil‐Ordóñez, Albert Gallego‐Gamo, Pau Sarró, Roser Pleixats, Carolina Gimbert‐Suriñach, Adelina Vallribera, Albert Granados

2025The Journal of Organic Chemistry12 citationsDOIOpen Access PDF

Abstract

In this work, we present a photoredox three-component reaction that enables the synthesis of medicinally relevant β-trifluoromethyl β-amino ketones from a N -trifluoroethylhydroxylamine derivative, styrenes and DMSO. Remarkably, fluoromethyl, difluoromethyl and pentafluoroethyl analogues are also accessed using the same reaction conditions. The mechanistic investigations, including radical trapping experiments, cyclic voltammetry, Stern–Volmer quenching studies and isotope labelling experiments support the photoinduced radical/polar crossover and Kornblum-type oxidation mechanisms. Finally, the applicability of the accessed organic skeletons is showcased by notable derivatization reactions.

Topics & Concepts

TrifluoromethylComponent (thermodynamics)ChemistryStereochemistryCombinatorial chemistryOrganic chemistryPhysicsThermodynamicsAlkylFluorine in Organic ChemistrySynthesis and Biological EvaluationRadical Photochemical Reactions
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