Reactions of steroidal 5,6-epoxides and cyclohexene oxide with aluminum alkoxides

Abstract

The isomeric 5,6a-and 5,6P-epoxycholestanes, in addition to an analogous series of compounds substituted at C-3 with hydroxy ( a or P stereochemistry) or ethylene ketal groups, have been treated with aluminum isopropoxide or tert-butoxide.The latter series of reactions did not give identifiable material, but aluminum isopropoxide gave products derived from epoxide opening and rearrangement in all cases. With epoxides unsubstituted at C-3, aluminum isopropoxide functioned as a Lewis acid in promoting epoxide rearrangements. In the presence of a C-3 alcohol function, additional products were obtained arising from fragmentation of the C-4,C-5 bond, or from p-elimination of the epoxide involving the loss of a C-7 hydrogen. Meerwein-Pondorff reduction of product carbonyl groups was also observed. C-3 ketal substituted epoxides were rearranged cleanly to 6-hydroxy-A4-3-ketones. Cyclohexene oxide reacted with aluminum isopropoxide (but not with tert-butoxide) to give two products arising from epoxide addition reactions. Structures for these products are proposed based on their 13C nmr spectra, and a possible route for their formation is presented. None of the epoxides examined in this study reacted with magnesium methoxide.HERBERT L. HOLLAND et SAEED R. KHAN. Can. J. Chem. 63, 2763 (1985. On a fait rkagir les epoxy-5,6a et -5,6P cholestanes ainsi qu'une sene de composts analogues substituks en C-3 par un groupement hydroxyle (de stkrtochimie a ou P) ou par un groupement tthyl&ne cttal avec I'isopropylate ou le tert-butylate d'aluminium. Les rkactions avec le tert-butylate ne donnent pas de produits identifiables; toutefois, lors des reactions avec I'isopropylate d'aluminium, on obtient dans tous les cas des produits qui rksultent d'une ouverture de I'tpoxyde suivie d'une transposition. Dans les cas des epoxydes qui ne sont pas substitues en C-3, l'isopropylate d'aluminium agit comme un acide de Lewis qui favorise les transpositions de I'Qoxyde. En presence d'une fonction alcool en C-3, on obtient des produits additionnels provenant soit d'une fragmentation de la liaison C-4, C-5 soit d'une elimination P de 1'Cpoxyde qui implique une perte d'hydrogkne en C-7. On a Cgalement observt une reduction de Meerwein-Pondorff des groupements carbonyls. Les tpoxydes ayant un substituant cttal en position C-3 se transposent proprement en hydroxy-6 A4 ccCtones-3. L'tpoxyde du cyclohexkne reagit avec I'isopropyl?te d'aluminium (mais non avec le tert-butylate) pour donner des produits dtcoulant de reactions d'addition sur 1'Cpoxyde. A partir des spectres de rmn du I3C, on propose des structures pour ces produits et l'on propose une voie possible pour leur formation. Aucun des epoxydes ttudiks dans ce travail ne rkagit avec le methylate de magnesium.[Traduit par le journal]The stereochemical control of product formation inherent in the epoxide opening reaction has ensured place for the latter in modem asymmetric synthesis (e.g. ref. 1). The opening of epoxides by nucleophiles may be assisted by Lewis acids (2); the latter reagents alon...

Synthesis of Deuterium-Labeled Steroid 3,6-Diols

“…The steroids 3 and 4 have 5-steroid nucleus that were confirmed by 13 4. Thus, as the result we obtained 5-cholestane-3,6-diol (3,6-coprostanediol, 3), 5-cholestane-3,6-diol (3,6coprostanediol, 4), cholest-4-ene-3,6-diol (5), cholest-4-ene-3,6-diol (6), and 5-cholestane-3,6-diol (7). Although these steroid diols have been reported many years ago [6][7][8][9], little or no NMR and MS characterization of these compounds were presented in literature.…”

“…Thus, as the result we obtained 5-cholestane-3,6-diol (3,6-coprostanediol, 3), 5-cholestane-3,6-diol (3,6coprostanediol, 4), cholest-4-ene-3,6-diol (5), cholest-4-ene-3,6-diol (6), and 5-cholestane-3,6-diol (7). Although these steroid diols have been reported many years ago [6][7][8][9], little or no NMR and MS characterization of these compounds were presented in literature. So we assigned all proton and carbon signals of 3-7 using 2D NMR experiments, including 1 H-1 H COSY, HSQC, HMBC, and ROESY (see Supplementary Materials).…”

“…The steroids 3 and 4 have 5-steroid nucleus that were confirmed by 13 C NMR signals of C-19 atoms at  C 26.0 and 23.8, respectively, shifted in the downfield region compared to 5-steroids [5] 6, and 5-cholestane-3,6-diol (7). Although these steroid diols have been reported many years ago [6][7][8][9], little or no NMR and MS characterization of these compounds were presented in literature. So we assigned all proton and carbon signals of 3-7 using 2D NMR experiments, including 1 H-1 H COSY, HSQC, HMBC, and ROESY (see Supplementary Materials).…”

Unexpected cyclisation of an acetylenic acetal: vinyl cation capture by internally transferred hydride

“…All the peak positions in the 13C NMR spectrum of the mixture matched those of a mixture (different proportions) of these dienes obtained by a different method. 10 The observed [aID of the mixture corresponds to the calculated [(xlD1l of a 4 : 1 mixture of cholesta-3,5-and 4,6-dienes.…”

Highly β‐Selective Epoxidation of Δ 5 ‐Unsaturated Steroids Catalyzed by Ketones

“…Compounds 8 a and 8 b (as a mixture in a ratio of 1: Epoxides 6 a and 6 b [26] (as a mixture in a ratio of 1:15.1), 7 a and 7 b [27] (as a mixture in a ratio of 1:10.4), 9 a and 9 b [28] (as a mixture in a ratio of 1:8.8), 10 a and 10 b [27] (as a mixture in a ratio of 1:11.6), 12 a, [29] 12 b, [30] 13 b, [30] 14 b, [31] 15 b, [32] 16 b, [33] 17 b, [18] 18 b, [34] 19 b, [18] 20 b, [35] and 21 b [36] have spectroscopic data which are identical with those reported in literature.…”