Synthesis of thyroid hormone analogues. Part 3. Iodonium salt approaches to SK&F L-94901

Abstract

The key step in the synthesis of L-3,5-dibromo-3′-[6-oxo-1,6-dihydropyridazin-3-yl)methyl]-thyronine, SK&F L-94901 (1), a novel, selective, and potent thyromimetic, is the formation of the hindered diaryl ether moiety. This paper describes an investigation into the formation of the required diaryl ether by copper-catalysed reaction both of symmetrical iodonium salts (2a) and (10) and mixed iodonium salts (2b–e) with protected dibromotyrosine (5). The importance of the counter-ion of the iodonium salt is discussed. This work is extended to a large-scale synthesis of SK&F L-94901 (1).