Synthesis of enantiopure B-nor-steroids by multiple Pd-catalyzed transformations

The synthesis of the novel enantiopure B-nor-steroid 9 is described employing a combination of a Suzuki- and a Heck-reaction. As substrates the 2-bromobenzylchloride (11) and the boronic ester 16 were used; the latter was prepared from the Hajos–Wiechert ketone derivative 17 in five steps. Noteworthy, the Heck-reaction was performed under microwave irradiation, which was much superior compared to the normal thermal reaction. The purpose of the described work is the design of novel estrogens, which bind to the β-unit of the maxi K+-channel located on the surface of the endothelium without showing the hormonal activity of estradiol 6.