Unsaturated A-homosteroids

Acid-Catalyzed Ring Enlargement Using Diazomethane 

A valuable extension of the diazomethane reaction for the preparation of A-homosteroids was discovered by Johnson, Neeman and Birkeland who found that a,j5-unsaturated ketones are homologated by reaction with diazomethane in the presence of either fluoroboric acid or boron trifluoride. The main product is formed by the insertion of a methylene group between the carbonyl group and the unsaturated a-carbon to give a / ,y-unsaturated ketone. 

An example is cholest-4-en-3-one (15a) which fails to react with diazomethane under normal conditions, but reacts rapidly with nitrogen evolution 

Although at equilibrium the j5,y-tautomer (16a) is preferred, some of the conjugated enone (17) can be obtained by acid-catalyzed equilibration. Hydrogenation of the A-homo-enone (16a) gives a mixture from which A-homo-5a-cholestan-3-one (5b) can be isolated. 

Extension of the acid-catalyzed diazomethane homologation to 17j5-hydroxyandrost-4-en-3-one propionate (15b) gives 17j5-hydroxy-A-homo-androst-4a-en-3-one propionate (16b) in 20% yield. 

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