Jeff McKenna, Global Discovery Chemistry

Global Discovery Chemistry

Cambridge, Massachusetts, United States

Enantioselective fluorination and trifluoromethylation are challenging synthetic operations and only recently have advances been made in this area. The incorporation of either motif into a molecule has the ability to drastically affect physicochemical, chemical, metabolic and biological activity of the parent compound or for the resulting fluorinated analog to be used as a radiotracer in PET imaging. We have recently developed a palladium-catalyzed reaction that achieves the carbo-fluorination of styrene via a proposed Pd(IV) intermediate. The reaction proceeds with complete regiocontrol and with high enantioselectivity. Our intent is to extend this carbo-fluorination methodology both with regard to its outcome, and its substrate scope while in parallel developing a robust analogous trifluoromethylation methodology. The program offers the opportunity to elucidate the mechanism of the carbo-fluorination reaction and harbors the potential for the design of further catalyst systems and so expand fluorination reaction paradigms.

We see the developed fluorination methods to be directly applicable for use in pharmaceutical research while the synthetic methodology at its center is at the forefront of modern method development using phase transfer and oganometallic catalysis. Our research program has been conducted in collaboration with Professor FD Toste (UC Berkeley) and will continue to be so; this collaborative research program will likely offer time in a leading academic center coupled with time in an industrial setting. Please also see for the opportunities presented in this collaborative program.

Selected Publications

Application of a deuterium replacement strategy to modulate the pharmacokinetics of 7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-(4-methoxy-2-methylphenyl)-2,6-dimethylpyrazolo[5,1-b]oxazole, a novel CRF-1 antagonist
Stringer RA, Williams G, Picard F, Sohal B, Kretz O, McKenna J, Krauser J.
Drug Metab. Dispos. 2014 May; 42(5):954-962

Asymmetric palladium-catalyzed directed intermolecular fluoroarylation of styrenes
Talbot EP, Fernandes Tde A, McKenna JM, Toste FD.
J. Am. Chem. Soc. 2014 March; 136(11):4101-4104

Gold catalysed redox synthesis of imidazo[1,2-a]pyridine using pyridine N-Oxide and alkynes
Talbot EP, Richardson M, McKenna JM, Toste FD.
Adv. Syn. Catal. 2014 March; 356(4):687-691

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