Regiospecific synthesis of 2-fluoro-3-O-methylestrone using caesium fluorosulfate

Abstract

The regiospecific synthesis of an A-ring fluorinated estrone is described. Treatment of the η⁶-arenetricarbonylchromium(0) complex 4, derived from 3-O-methylestrone, with butyllithium followed by transmetallation to the arylboronic acid was found to give a single regioisomer. This could be elaborated further to give 2-fluoro-3-O-methylestrone in 27% yield using caesium fluoroxysulfate. The fluorination step was found to be sufficiently rapid to be of potential use in PETT applications with the ¹⁸F radioisotope.