5a-Cholest-13 -ene

This reaction sequence proceeds by cis addition of deuterium and the reduction products usually exhibit high isotopic purity. For example, 5a-cholest-2-ene (136), which is known to give a product of very unsatisfactory isotopic purity when deuterated with heterogeneous catalysts (see section V-A), gives 2<, 3 -d2-5a-cholestane (137) with better than 95% isotopic purity in homogeneous solution. ... 

Reduction of 5a-Cholest-2-ene with Deuterium and Tris-(tri-phenylphosphine)-chiororhodium... 

The rhodium catalyst (46 mg) is dissolved in acetone (10 ml) in a microhydrogenation apparatus which is then flushed three times with deuterium gas. After stirring the solution in an atmosphere of deuterium for about 1 hr the deuterium uptake ceases and constant pressure is attained. 5a-Cholest-2-ene (136, 19.5 mg) is added and the stirring continued until deuterium uptake ceases (about 3/4 hr). The solvent is evaporated to dryness and the residue is extracted with hexane and the resulting solution filtered through a small alumina column (3 g, activity 111). Evaporation of the hexane gives 2, 3 -d2-5oc-cholestane (137) 18 mg, 92% mp 78-79° isotope composition 94%d2,5%d, andl%do. ... 

Deuterioboration of 5a-cholest-2-ene (171), followed by oxidation of the alkylborane intermediate with hydrogen peroxide in the presence of sodium hydroxide, illustrates the application of this method for the preparation of c/5-deuterium labeled alcohols.(For the preparation of tra 5 -deuterium labeled alcohols see section VII-A.) The predominant reaction product is 2a-di-5a-cholestan-3a-ol (172, 1.03 D/mole) which is accompanied by 3a-di-5a-cholestan-2a-ol (173) and other minor products." ... 

Iodine isocyanate was used to synthesize the first steroidal aziridine, 2, 3 -iminocholestane (95). from 5a-cholest-2-ene (91). This reaction sequence which is believed to proceed through a three-membered ring iodonium ion (92) illustrates the limitation of pseudohalogen additions for the synthesis of -aziridines. The iodonium complex forms from the least hindered side (usually alpha) and is opened tmK5-diaxially to give a -oriented nitrogen function. The 3a-iodo-2 -isocyanate (93) is converted by treatment with... 

A solution of 5 g (14 mmoles) of 5a-cholest-2-ene in 100 ml ethyl acetate and 8 ml of 2.8 M (22 mmoles) cyanogen azide (CAUTION See Chapter 15 and ref. 139b) in ethyl acetate is heated at 50-53° for 24 hr, during which time about 22 mmoles of nitrogen is evolved. Solvent is removed by evaporation and the residue is applied in benzene to a column of 160 g of neutral alumina (activity grade III). Elution with petroleum ether-benzene (1 1) gives 1.6 g of... 

To a mixture of ethyl 5a-cholestan-3-one 2a-xanthate (2 g, 3.95 mmol) and 100 ml methanol is added sufficient ether to completely dissolve the solids. Sodium borohydride (90 mg, 2.36 mmol) is added directly to the reaction flask and the solution is stirred at room temperature for 4 hr. (The use of an excess of sodium borohydride and an extended reaction time produces 5oc-cholestan-2a,3a-thiirane.) The reaction is diluted with 200 ml ether and washed several times with ca. 100 ml water, dried (MgS04) and the solvent is removed under vacuum. The crude sticky gum is chromatographed on a column of 85 g silicic acid. The hexane eluates contain 5a-cholest-2-ene. Ethyl 5a-cholestan-3a-ol 2a-xanthate is obtained in ca. 30% yield by subsequent elution with benzene hexane (1 7) and the desired ethyl 5a-cholestan-3 -ol 2a-xanthate is eluted with ether hexane (1 3) in ca. 30% yield. 

The configurations assigned to (8) and (9) were established by comparison with the products resulting from epoxidation of 3-methyl-5a-cholest-2-ene followed by reduction with lithium aluminum hydride to the alcohol (9). The usual /ra 5-diaxial epoxide opening requires that the hydroxyl group, formed by reduction, is axial as shown in (9). 

Levisalles and co-workers have prepared A-homo-5a-cholestan-4-one by the dibromocarbene procedure starting with 3-methoxy-5a-cholest-2-ene. Wieland and Anner have converted 19-mesyloxy-A -3-keto steroids into... 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

Because of the many examples of such activation of metal powders by TCS 14 only a limited and arbitrary number will be discussed here. The Clemmensen-type reduction of ketones such as cyclohexanone with Zn powder in the presence of TCS 14 affords, via 2082, 2084, and 2085, cyclohexene and, via 2082, O-silylated pinacol 2083 [19, 20]. Ketones such as 5a-cholestan-3-one 2086 are reduced by Zn dust-TCS 14 in TFIF, in ca 65-70% yield, to give 5a-cholest-2-ene 2087 and ca 5% 5a-cholest-3-ene [21] (Scheme 13.8). 

Conflict between electronic (Markovnikov) and conformational control in the electrophilic additions of alkenes is well known in steroids and generally leads to the conformationally preferred diaxial addition product. Methoxybrominations of 2-methyl-5a-cholest-2-ene (69) and its 3-methyl isomer (71) illustrate control by a combination of conformational and electronic factors the products indicate that the first-formed bromonium ion equilibrates between the 2a,3a and the 2/3,3/3 configurations before suffering nucleophilic attack by methanol. The major product (72) from the 3-methyl compound results from methanolysis of the less stable 2/8,3/3-bromonium ion, axial attack at the tertiary C-3 being the most favourable mode of reaction.95... 

Oximes, Tosylhydrazones, and Related Derivatives.—Ketoximes afford enimides in refluxing acetic anhydride-pyridine.181 Theproduct (207) from 5a-cholestan-3-one oxime (206), for example, gave 3-acetylamino-5a-cholest-2-ene (208) in 93% yield after chromatography on alumina. Use of succinic instead of acetic anhydride, with pyridine, gave the enimide (209) which was stable to chromatography. A radical mechanism is proposed. Reduction of ketoximes by Cr11, V11, or Tiin salts in acetic anhydride affords the same enamides, by acetylation of the intermediate imines. The... 

Sensitized photo-oxygenation of 3-morpholino-5a-cholest-2-ene (320) led to a mixture of the 2,3-dione (322) and the 3-morpholino-3-en-2-one (323). Model experiments at low temperature confirmed the formation of an unstable dioxetan (321) as the key intermediate, formed by addition of singlet oxygen on to the olefinic bond of the enamine.253... 

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