Stereochemical requirements in intramolecular cyclizations

Friedel-Crafts acylation. Posner el al. have developed a remarkably efficient route to the methyl ether of the steroid 11-oxoequilenin (5) from 2-methyl-2-cyclopentenone (1). jS-Addition of the organocoppermagnesium reagent 2 to 1 followed by a-alkylation with ethyl iodoacetate proceeds stereospecifically to give the secosteroid 3 in 94% yield. The final step requires an intramolecular Friedel-Crafts acylation, a reaction that has proved troublesome in previous syntheses of steroids via 9,11-secosteroids. And indeed attempts to cyclize the free acid corresponding to 3 with HF proceeded in yields of 10%. However, cyclization of the ketal acid 4 gives stereochemically pure 5 in 75% yield based on recovered secosteroid. The overall yield from 2-bromo-6-methoxynaphthalene is 52%. 

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