30 Years with ortho-directed hydrogen isotope exchange labelling

✍ Scribed by W. J. S. Lockley

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 169 KB
• Volume: 50
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1421

✦ Synopsis

Abstract

Over a 30‐year period, a range of directed exchange methods have been developed to label target molecules with isotopic hydrogen. Among these methods, those involving ortho‐direction have proved particularly useful for labelling a wide selection of drugs, drug candidates, agrochemicals, biochemicals, natural products and other significant agents with both tritium and deuterium. The approach has involved the identification of new catalysts for ortho‐directed exchange including RhCl~3~ · 3H~2~O for the one‐step labelling of carboxylic acids, amides, anilides, etc., with deuterium at high abundance, and with tritium at low and high specific activities from an isotopic water donor; CODIr(CH~3~ · CO · CH~2~ · CO · CH~3~), a similar and often more active catalyst with a somewhat different spectrum of directing substituents; CODIr(CF~3~ · CO · CH~2~ · CO · CF~3~), a catalyst for the labelling of benzylamines, anilines and heterocyclics utilizing isotopic hydrogen gas as the donor, and which is active even in dipolar aprotic solvents; and latterly, solid‐phase iridium(1)‐based catalysts, with activities similar to the Heys and Crabtree catalysts, which have significant advantages over their homogenous counterparts in tritium‐labelling via the ortho‐direction approach. Copyright © 2007 John Wiley & Sons, Ltd.