New synthesis of a selective estrogen receptor modulator using an enatioselective phosphine-mediated 2+3 cycloaddition

A new synthetic approach to the selective estrogen agonist 1 is described. The key steps in the route are a phosphine catalyzed 2+3 cycloaddition between an indanone enone and allenyl methyl ketone, and an unusual Robinson annulation to afford a bicylco[3.2.1]octane. The potential benefits of the new route are discussed along with efforts to render the approach asymmetric.

Graphical abstractDownload full-size image