Editorial pubs.acs.org/OPRD
Invited Academic Review on Late-Stage Fluorination
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luorine confers beneficial properties to active substances in the pharmaceutical, agrochemical, and fine chemicals industry by way of modulating molecular properties such as lipophilicity, solubility, bioavailability, and metabolic stability. Last, but not least, it is a means to find novel structures in fields where copious patent protections have narrowed down the “free chemical space” drastically. Most fluorination techniques are characterized by harsh conditions (fluorine gas, HF, high/ low temperatures, toxic reagents such as DAST) that restrict the substrate scope to simple starting materials with a confined set of functional groups. There is a growing need for methods to introduce the fluorine atom late in the synthesis, i.e., using highly functionalized substrates, allowing for a completely different route design. Professor Tobias Ritter and his group at Harvard University are at the forefront of this field of research. We are honored to present this account on late-stage fluorinations, ranging from his mechanistic research on Pd-catalyzed fluorinations and applications thereof with highly functionalized substrates to a recent synthesis of 18F-PET tracers used for in vivo imaging studies in animals. In analogy to the recently characterized naturally occurring fluorinases that convey fluorine to more elaborate substrates, these purely chemical, late-stage fluorination methods have opened doors to thus far “impossible” transformations. In view of the importance of fluorine in many fields of our life, we are sure that these pivotal results will trigger even more practical ways of decorating functionalized substrates with fluorine atoms. We warmly thank Professor Ritter for his contribution to Organic Process Research & Development.
Stefan Abele* Process Research Chemistry, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil, Switzerland
Hans-Jur̈ gen Federsel
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Pharmaceutical Development, AstraZeneca, Macclesfield, Cheshire SK10 2NA, United Kingdom
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Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
© XXXX American Chemical Society
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dx.doi.org/10.1021/op5000539 | Org. Process Res. Dev. XXXX, XXX, XXX−XXX
