Methyl groups angular, elimination

Interest in the synthesis of 19-norsteroids as orally active progestins prompted efforts to remove the C19 angular methyl substituent of readily available steroid precursors. Industrial applications include the direct conversion of androsta-l,4-diene-3,17-dione [897-06-3] (92) to estrone [53-16-7] (26) by thermolysis in mineral oil at about 500°C (136), and reductive elimination of the angular methyl group of the 17-ketal of the dione [2398-63-2] (93) with lithium biphenyl radical anion to form the 17-ketal of estrone [900-83-4] (94) (137). 

Elimination of the angular methyl group from [4 + 2]-adducts of 82 gave monobenzoporphyrins (84CC1047). 

The tendency to form the stable aromatic system is so strong that, when necessary, groups can be eliminated for example, a methyl group located at the point of fusion between two rings, a so-called angular methyl group (Sec. 15.16). 

Transannular dehydrocyclization of methylcycloalkanes may also be regulated by conformational or other characteristics of the hydrocarbon. In the case of methylcyclononane, the predominant formation of cis-8-methyl-hydrindane with its methyl group in the angular position and of products derived from it (769) suggests that the transannular dehydrocyclization proceeds chiefly with elimination of the intraannular hydrogen atom located on the tertiary carbon atom, and therefore with the methyl group in the extraannular position (Scheme 85). But other bicyclic products are also obtained in appreciable amounts, so that it is not clear whether the direction of dehydrocyclization is determined by the presence of a hydrogen atom at a tertiary carbon atom or by some conformational peculiarities of the molecule. 

The selective reduction of the adduct (235) led to the triketone (236). The passage from the latter to the natural steroids requires epimerization at Ci4, the elimination of the 15-oxo group and the A ( )-bond, the introduction of the angular methyl group, and the conversion of the six-membered ring D into a five-membered ring. At the present time, the first three problems have been solved successfully and the synthesis of the 18-nor-D-homoandrostanes with the natural configuration has been achieved (326, 327). Isomerization of the cis-syn triketone (236) into the trans-anti-isomer (239) was carried out by the action of alkaline alumina. The reduction of the triketone (239) with subsequent acetylation led to the... 

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