The preparation of thiathromboxane analogues and a formal total synthesis of dithiathromboxane A2 based on conjugate addition reactions of thiin-4-ones

Abstract

The conjugate addition reactions of thiin-4-one and 3-methoxycarbonylthiin-4-one have been investigated. In contrast to thiin-4-one its 3-methoxycarbonyl derivative undergoes conjugate addition with a range of organocopper reagents, the most efficient being copper-catalysed Grignard reagents. The resulting adducts have been converted into 2-substituted thiin-4-ones by two procedures. This methodology has been used to prepare thiathromboxane analogues (12a), (12b), and (13) and as part of a ten step formal synthesis of dithiathromboxane A₂(9).