Platinum Metals Rev., 2001, 45, (2), 69
Thiazepinones Synthesis with Rhodium
Thiazepinones are pharmaceuticals with potential use in the treatment of heart and inflammatory diseases. The 7-membered heterocycles have been prepared in multistep syntheses in which chirality is introduced before or during a transformation.
Researchers at the University of Ottawa, Canada, now report the synthesis of thiazepinones using cyclohydrocarbonylative ring expansion of acetylenic thiazoles in the presence of CO and H2, via the zwitterionic rhodium complex catalyst (η6-C6H5BPh3)-Rh+(l,5-COD) with added triphenyl phosphite (B. G. Van den Hoven and H. Alper, J. Am. Chem. Soc ., 2001, 123, (6), 1017–1022).
The transformation of the simple and functionalised 5-membered acetylenic thiazoles with CO and H2 to 7-membered 2-(Z )-6-(E )-4H-[1,4]-thiazepin-5-ones occurred in 61 to 90 per cent yields with good chemo- and regioselectivities, at 70–110°C, after 18 to 36 hours. A model substrate of 2-hex-1-ynylthiazole was used to optimise the cyclohydrocarbonylation and ring expansion of 2-acetylenic thiazoles. The acetylenic unit can have various substituents in positions 4 and 5 of the thiazole ring as well as alkyl-, ether-, ester-, vinyl-, and aryl-substituted alkynes at position 2. The process is general and may be pharmaceutically interesting.