Mild, Organo-Catalysed Borono-Deamination as a Key to Late-Stage Pharmaceutical Precursors and 18F-Labelled Radiotracers

Raúl M Pérez-García; Patrick J Riss

doi:10.3389/fchem.2022.884478

Mild, Organo-Catalysed Borono-Deamination as a Key to Late-Stage Pharmaceutical Precursors and ¹⁸F-Labelled Radiotracers

Front Chem. 2022 Apr 26:10:884478. doi: 10.3389/fchem.2022.884478. eCollection 2022.

Authors

Raúl M Pérez-García¹, Patrick J Riss^{1

2

3

4}

Affiliations

¹ Section of Organic Chemistry, Department of Chemistry, University of Oslo, Oslo, Norway.
² Division of Clinical Neuroscience, Oslo University Hospitals HF, Oslo, Norway.
³ GIGA Cyclotron Research Centre, Department of Chemistry, Liège, Belgium.
⁴ Department of Chemistry, Johannes Gutenberg-University, Mainz, Germany.

Abstract

A tris(pentafluorophenyl)borane catalysed method for the synthesis of boronic acid esters from aromatic amines in yields of up to 93% was devised. Mild conditions, benign reagents, short reaction times, low temperatures and a wide substrate scope characterize the method. The reaction was found applicable to the synthesis of boronic acid ester derivatives of complex drug molecules in up to 86% isolated yield and high purity suitable for labelling. These boronates were subsequently labelled with [¹⁸F]fluoride ion in radiochemical yields of up to 55% with and even without isolation of the boronate-intermediate.

Keywords: aromatic amines; aryl boronates; boronato-deamination; drug molecules; lewis acid-catalysis; positron emission tomography; radiofluorination.