PhenoFluor^™ Solution for Convenient, One-step Deoxyfluorination

The functional-group-tolerant, one-step conversion of phenols to aryl fluorides is a highly desirable process. PhenoFluor™ solution, an innovative reagent developed by Ritter and co-workers,¹ provides a straightforward method to fluorinate alcohol and phenols without preactivation and regioselectively fluorinate highly functionalized late-stage intermediates. In collaboration with Tobias Ritter, we now offer two convenient formulation of PhenoFluor™ solution that can be readily used outside of the glovebox.

General Reaction Scheme

PhenoFluor™ solution is a thermally stable deoxyfluorinating agent that delivers aryl fluorides from phenols in a one-step, high–yield, ipso substitution reaction. The method is operationally simple, regiospecific, scalable, and compatible with a variety of functional groups including amines, aldehydes, and heterocycles. More recently, it was reported that PhenoFluor™ solution can be used in a late-stage functionalization (LSF) strategy by deoxyfluorinating several natural products and drug-like molecules in a highly regioselective fashion.

Representative Substrate Scope

References

1. Tang P, Wang W, Ritter T. 2011. Deoxyfluorination of Phenols. J. Am. Chem. Soc.. 133(30):11482-11484. https://doi.org/10.1021/ja2048072

2. Sladojevich F, Arlow SI, Tang P, Ritter T. 2013. Late-Stage Deoxyfluorination of Alcohols with PhenoFluor. J. Am. Chem. Soc.. 135(7):2470-2473. https://doi.org/10.1021/ja3125405

3. Fujimoto T, Becker F, Ritter T. 2014. PhenoFluor: Practical Synthesis, New Formulation, and Deoxyfluorination of Heteroaromatics. Org. Process Res. Dev.. 18(8):1041-1044. https://doi.org/10.1021/op500121w

4. Fujimoto T, Ritter T. 2015. ChemInform Abstract: PhenoFluorMix: Practical Chemoselective Deoxyfluorination of Phenols.. ChemInform. 46(25):no-no. https://doi.org/10.1002/chin.201525084

PhenoFluor is a trademark of SciFluor Life Sciences, LLC.

Sure/Seal is a trademark of Merck KGaA, Darmstadt, Germany and/or its affiliates.