Dienones thiol addition

The first 1,6-addition reactions of thiolates to steroid dienones were examined well before the discovery of the antiestrogenic properties of 7o -substituted steroids. Ralls and coworkers129 and Djerassi and coworkers130 studied thiol additions to A3,5-steroids for example, the reaction of 3,5-cholestadien-7-one with ethanethiol was reported to proceed with high 1,6-regioselectivity and -stereoselectivity (equation 47)129. In a series of papers, Brueggemeier and coworkers131-137 described the synthesis and biochemical evaluation of numerous 7at-sul fur-substituted steroids which were prepared by Michael addition to steroid dienones. Thus, 4,6-androsta-3,17-dienone was treated with various... 

The formation of a titanium chelate enables regiochemical control of the conjugate addition of a thiol to an a,/3,y,d-dienone, as shown in Eq. (307) [694]. Simple base-catalyzed reaction occurred selectively at the terminal (d) position of the substrate. When, however, a similar reaction was performed in the presence of TiCU, addition occurred exclusively at the position / to the carbonyl group, where the intermediate can take the chelate form, as depicted. The same observation was also noted for the corresponding conjugated trienone. A similar reaction has been applied to the cis —> trans isomerization of conjugated dienoates [695]. 

---