Saturated A-homo ketones

Nelson and Scliut investigated the reaction of 5a-cholestanone (lb) with diazomethane in a search for a direct, one-step preparation of A-homo ketones. Using a large excess of diazomethane generated in situ from A-methyl-nitrosourea with potassium hydroxide in ether-methanol at 0°, 5a-cholestanone (lb) is converted into the 7-membered ring homolog (3b) as the predominant product. Both theoretically possible A-homo ketones can be expected with an unsymmetrically-substituted cyclohexanone such as 5a-cholestanone (lb). 

Treatment of 5a-cholestanone (lb) in this way gives a mixture from which 7-and 8-membered ring ketones can be isolated. The yields of crude ketones are A-homo-4-one (3b), 40-50% A-homo-3-one (5b), 10% and a A-bis-homo ketone 5 %. The structure of the bis-homocholestanone has not been rigorously established. 

To establish the structure of A-homo ketone (3b) Nelson and Schut repeated the TifFeneau ring enlargement of 5a-cholestanone [(Ib) (6a) (6b) - (7)] and obtained a ketone identical with A-homo ketone (3b). 

The position of the keto group of A-homo-5a-cholestan-3-one (5b) was determined by Nelson and Schut by an unambiguous synthesis of ketone (5b) involving bis-homologation of 2,3-seco-5a-cholestane-2,3-dioic acid (8) using the Arndt-Eistert sequence [(9) (11)]. 

In the latter process Dieckmann cyclization of diester (11) using high dilution conditions failed. However, A-homo-5a-cholestan-3-one (5b) identical to the product of diazomethane ring enlargement of (lb) was obtained in 35 % yield when diester (11) was hydrolyzed to the bis-homo diacid and this converted to the thorium salt and pyrolyzed. 

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II. RING A EXPANSION A-HOMOSTEROIDS A. Saturated A-Homo Ketones 1. Tiffeneau Ring Enlargement... 

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