Baeyer‐Villiger oxidation tuned to chemoselective conversion of non‐activated [¹⁸F]fluorobenzaldehydes to [¹⁸F]fluorophenols

Abstract

A reaction pathway via oxidation of [ 18 F]fluorobenzaldehydes offers a very useful tool for the no-carrier-added radiosynthesis of [ 18 F]fluorophenols, a structural motive of several potential radiopharmaceuticals. A considerably improved chemoselectivity of the Baeyer-Villiger oxidation (BVO) towards phenols was achieved, employing 2,2,2-trifluoroethanol as reaction solvent in combination with Oxone or m-CPBA as oxidation agent. The studies showed the necessity of H 2 SO 4 addition, which appears to have a dual effect, acting as catalyst and desiccant. For example, 2-[ 18 F]fluorophenol was obtained with a RCY of 97% under optimised conditions of 80°C and 30-minute reaction time.The changed performance of the BVO, which is in agreement with known reaction mechanisms via Criegee intermediates, provided the best results with regard to radiochemical yield (RCY) and chemoselectivity, i.e. formation of [ 18 F]fluorophenols rather than [ 18 F]fluorobenzoic acids. Thus, after a long history of the BVO, the new modification now allows an almost specific formation of phenols, even from electron-deficient benzaldehydes. Further, the applicability of the tuned, chemoselective BVO to the n.c.a. level and to more complex compounds was demonstrated for the products n.c.a. 4-[ 18 F]fluorophenol (RCY 95%; relating to 4-[ 18 F]fluorobenzaldehyde) and 4-[ 18 F]fluoro-m-tyramine (RCY 32%; relating to [ 18 F]fluoride), respectively.

Green Oxidation of Ketones to Lactones with Oxone in Water

“…Therefore, many research efforts have addressed the development of procedures avoiding the use of water or minimizing its drawbacks. Examples include the use of wet-alumina or silica-gel-supported KHSO 5 in DCM of Oxone in ionic liquids, followed by treatment with DCM, in DMF, in water, and DCM in the presence of a phase transfer catalyst (PTC), or in trifluoroethanol . As can be seen, despite the employment of a clean oxidant, the replacement of water is not accomplished according to principles of sustainable and scalable procedures.…”

Editorial for the special Issue “Jörg Steinbach”

“…In this regard, this special issue reflects all the aspects of radiopharmacy, starting from improved separation techniques for the production of 64 Cu, followed by new methods for the introduction of fluorine‐18 into aromatics involving the Baeyer‐Villiger‐oxidation or by ruthenium‐catalyzed cycloaddition reactions to green radiochemistry approaches . The identification of receptor ligands precedes radiotracer development as aptly exemplified by the design of novel fluorinated benzo[7]annulen‐7‐amines as GluN2B‐antagonists or preparation of the 64 Cu‐labeled α‐MSH peptide NAP‐NS1 .…”