Syntheses via biphenyl derivatives

The methyl ether of 14-isoestrone (485), with an IR spectrum identical with that of the d-enantiomer obtained by partial synthesis from natural estrone was synthesized by an analogous method from the 14)S carboxy-diester (476) cyclization to (480), hydrogenolysis to (482), extension of the side chain, and pyrolysis over lead carbonate [225, 241]. 

Banerjee and Sivanandaiah [573-576] have developed another route for the stereospecific synthesis of (478). Condensation of the amine (496) ob- 

Finally, the third method for synthesizing (478), developed by Johnson et al.[577,578], also starts from the Mannich base (496). Its condensation with cyanoacetic ester led to the cyanoke toes ter (493), which, by the Stobbe reaction with dimethyl succinate,formed compound (492). On hydrogenation of the double bond and angular methylation, this was converted into the cyanoester (489) which, in a similar manner to the preceding case, gave the intermediate (478) on treatment with methanolic hydrogen chloride. 

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Syntheses via Biphenyl Derivatives. The main content of this group of syntheses is Johnson s so-called second synthesis of estrone (Scheme 46) and the production of intermediates for it (Schemes 47). 

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