Synthesis Fluoxymesterone

scheme showing full synthesis of fluoxymesterone andrestenedione

steptwo: 11α-hydroxyl of starting material (1.16) sulfonylated p-toluenesulfonyl chloride; addition of trimethylamine (base) deprotonates 11α-carbon, yielding (e2) elimination of tosylate (pka - 5) give olefin (1.17). stereospecificity of reaction between olefin , hypobromous acid (hobr) in base, n-bromosuccinimide (nbs), determined formation of bromonium intermediate; electrophilic bromonium cation approaches ring’s less sterically hindered α-face , attacked π-electron density of alkene. hydroxide ion attacks above ring (β-face) @ 11-carbon, resulting in structure (1.18) stereospecific addition of hydroxyl , bromine across double bond. addition of sodium hydroxide results in deprotonation of 11α-hydroxyl, , subsequent structure undergoes intramolecular sn2 epoxy ring formation. epoxy ring of β-epoxide (1.19) protonated give oxironium ion intermediate. in concerted process, fluoride attacks ring’s α-face below, 1 of 2 oxygen-carbon bonds broken on opposite face; hence regenerating 11α-hydroxyl trans fluorine substituent. resulting structure (1.20) androgenic steroid, fluoxymesterone.