Syntheses of Estrone requiring a Resolution Stage

Based on the use of 4-methoxybenzocyclobutene-1-carboxylic acid, racemic homoestrone has been synthesised (ref. 124). A strategy based on boron annulation led not directly to estrone but to a synthesis of norpregnenolone which was then degraded by standard procedures to afford estradiol derivatives (ref. 125). 

Benzocyclobutene derivatives have also been used to alkylate a bicyclo[2.2.1] heptane which after transformation to the appropriate vinyl derivative has been thermolysed to yield the the tetracyclic structure of estradiol methyl ether (ref. 126) which latter upon oxidation with Jones reagent and demethylation ot the 

THFiCHjNj (Vi) Pt02,H2, (vii) LAH,THF,(viii) 2-N02C6H,SeCN, Bu3P,THF 50%H2O2,THF,(ix)1,2-Cl2CeH A 

By the use of the chiral bromo precursor of the bicycioheptane (at step i) an asymmetric synthesis of estrone was envisaged by the authors, in a highiy novel approach an alkylation reaction of a diyne with a vinyicyciopentene derivative has given an intermediate which by cobalt-mediated 

Quinodimethanes have been employed in a stereoselective synthesis (ref. 128) of estrone. A silicon-stabilised benzylic carbanion was obtained, avoiding lithiation of the methoxy-substituted ring, from the intermediate [2-[(trimethylsilyl)methyl]-5-methoxybenzyl]dimethylamine and after alkylation with the requisite cyclopentano component, generation of the quinodimethane structure with CsF afforded racemic estrone methyl ether. 

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