Stereo and chemical course of acid-catalyzed double bond migration of cholesta-5,7-dien-3 beta-ol to 5 alpha-cholesta-8,14-dien-3 beta-ol

Acid-catalyzed double bond migration of steroid 5,7-dienes to the 5 alpha-8 ,14-dienes, a well-known reaction in steroid chemistry, was reinvestigated by using cholesta-5,7-dien-3 beta-ol 1, and the stereo and chemical course of this reaction was detailed. Treatment of 1 with 36% hydrochloric acid in refluxing ethanol for 3 h afforded a 6:11:65:16:2 mixture of dienols (93%) : 5 alpha- and 5 beta-cholesta-6,8(14)-dien-3 beta-ols 7a,b, 5 alpha- and 5 beta-cholesta-8,14-dien-3 beta-ols 2a,b, and 5 alpha-cholesta-14,16-dien-3 beta-ol 10a, along with a mixture of enones (1.7%): 5 beta-cholest-8(14)-, 5 beta-cholest-14- and 14-epi-5 beta-cholest-8-en-3-ones 11-13. The experi ments using 7a,b and 2a,b suggested the reaction sequence: 1 --> 7a,b<->7,1 4-dienols 8a,b<->2a,b<->8(14),15-dienols 9a,b<->10a,b, in which 8a,b<->9a,b should be also implicated. The initial step, 1 to 7a,b proceeded irreversi bly with the stereoselectivity, ca. 7:3 of 5 alpha-H to 5 beta-H. Dienols 7 a, 8a, 2a and 10a with 5 alpha-H were identified, which were equilibrated a t 6:0:92 :2. Among dienols with 5 beta-H, only 7b and 2b were identified, w hich were equilibrated at 2:98, and this interconversion proceeded in compe tition with an intramolecular hydride shift from the C-3 alpha to C-6 alpha of 7b, leading to the formation of a mixture of enones 11-13. The consider able difference in activation energies between 1 --> 7a,b and 7a,b --> 8a,b /11-13 realized the predominant formation of 7a,b: by treatment at 30 degre es C for 44 h, 1 gave a 53:27:5:15 mixture (94%) of 7a, 7b, 8a and 2a.