2-Cholestene

Reduction of 3-Nitro-2-cholestene. - Zinc dust (dOOmg) was added in portions during 1 hr to a stirred warm (4(fC) suspension of 250 mg of 3-nitro-2-cholestene in 15mL of acetic acid and 0.5 ml of water. After 4 hr reflux, the mixture was Altered hot and the zinc washed well with hot HOAc. Addition of water and extraction with ether gave 116mg of product."... 

Iodine azide adds stereo- and regio-specifically to 2-cholestene giving a frans-diaxial adduct with azide at the 2-position, a consequence of attack by I from the less hindered face of the steroid. With 1-hexene the addition proceeds regiospecifically to yield the secondary azide, most likely via a three-mem-bered iodonium ion intermediate.111 With (Z)-2-octene, BrN3 addition gives a single adduct in 71% yield... 

Functionalized ethylene oligomer ligated rhodium(I) complexes were prepared and the hydrogenation of various alkenes including 1-octene, delta-2-cholestene, cyclooctene, cyclododecene, styrene, alpha-methylstyrene was studied 94). 

The photooxygenations of 3-methyl-2-cholestene and 2-methyl-2-cholestene give quite different patterns of product regio- and stereochemistry70. 

The stereochemistry of the major adduct was elucidated by H NMR and by conversion to the known 3/i-nitrocholestane. The corresponding aziridine could not be prepared, since the reduction with lithium aluminum hydride or zinc gave 2-cholestene, and treatment with iron(II) sulfate and hydrochloric acid gave starting material only. 

This is surprising, since the reaction of dinitrogen tetroxide with (E)-, 2-diphenylethylene in diethyl ether produced a 3 2 mixture of diastereomeric l,2-dinitro-l,2-diphenylethanes134 The reaction of 2-cholestene with dinitrogen tetroxide/iodine afforded 2/ -iodo-3a-nitro-5oi-chole-stane, this was also the product obtained by the addition of nitryl iodide (see previous section). 

The addition to steroidal alkenes promoted by chromium(II) chloride77 78, as well as thermal and photolytic additions, are predominantly trans 0. 2-Cholestene underwent thermal addition of ethyl dichlorocarbamate to give 2j8-chloro-3a-ethoxycarbonylaminocholestane80. Low yields of adducts were obtained from 3j8-acetoxy-5-androsten-17-one80. 

The diaxial 2/ -acetylamino-3/ -bromocholestane, obtained in situ from 2-cholestene, underwent direct cyclization under the reaction conditions, to give the corresponding . v-4,5-dihydrooxa-zole, which, in the presence of an excess of base, was converted to the cw-amido alcohol 1542. 

In 1913, Kishner observed in one instance that under standard Wolff-Kishner reduction conditions, 2-hydroxy-2,6-dimethyloctan-3-one underwent eliminative reduction upon treatment with hydrazine hydrate and base at elevated temperatures to afford 2,6-dimethyloctan-2-ene (Scheme 7). This same reaction was later found to occur in the case of a-methoxy ketones and has since been referred to as the Kishner eliminative reduction. The reaction entails initial formation of the hydrazone and elimination of the a-substituent to afford the intermediate alkenyldiazene, which subsequently collapses to the desired alkene. Given the facile transformation of ketones into a-halo ketones, these conditions have been used to introduce alkenes regioselectively in the 2a-halocholestan-3-one series as shown in Scheme 8. Yields of 2-cholestene parallel the resistance of the a-halogen to undergo competitive elimination reactions. 

This reaction has been utilized in the synthesis of azidosteroids ". Addition to 2-cholestene (224) occurs regioselectively and adducts 225 and 226 have been isolated in 37% and 27% yield respectively. By comparison, ionic addition leads to the /ranj-diaxial product (227). Such differing orientations of the products obtained from homolytic and heterolytic addition may be synthetically valuable. 

Ketenes add to the least hindered face of an alkene preferentially. Selective addition to one face of a cycloalkene is often observed. Addition of dichloroketene to 2-cholestene gives >80% of the cyclobutanone shown. 

Photooxidation of 3-morphohno-2-cholestene (4) at -78° give a 1 1 mixture of 3-morpholino-3-cholestene-2-one (5) and cholestane-2,3-dione (6). 

In aqueous 98.7% dioxane, perchloric acid catalyzes the isomerization of 3-methylenecholestane to 3-methyl-2-cholestene ,... 

A soln. of p-toluenesulfonic acid in acetic anhydride added to a stirred soln. of cholestanone 3-a-0-y -S-ethylene hemithioketal in methylene chloride, after 45 min. cooled to 0°, treated with more acetic anhydride and pyridine 2-(2 -cholesten-3 -yl)-3-( -acetylthioethoxy)-2-cholestene. Y 85%. F. e., also from ketals and enol-ethers, s. G. Karmas, J. Org. Chem. 33, 2436 (1968). 

Cholestene, VIII, 285 Cholestenone, activity, IX, 243 dihydrocholesterol and, IX, 259 preparation of labeled, IX, 243 A Cholesten-3-one,... 

A soln. of 5a,6a-epoxy-2-cholestene and 2,6-dichlorohenzoic acid in dry benzene refluxed 11.5 hrs. 6j -(2,6-dichlorobenzoyloxy)-2-cholesten-5a-ol. Y 71%. — The ester could not be prepared from the glycol with the sterically hindered 2,6-dichlorobenzoyl chloride. K. D. McMichael and G. A. Selter, J. Org. Ghem. 50,2549 (1965). 

Yields of nitrile varied from 35 to 72% according to the nature of the substituents. 2-Cholestene behaves similarly. The epoxyazide is a possible intermediate for this and a similar reaction in which cyclic alkenes were treated [138] with phenyliodo diacetate-trimethylsilyl azide, Phl(OAc)2Me3SiN3, for example ... 

A soln. of 2a-bromocholestanone in cyclohexene added dropwise with stirring during 10 min. to a refluxing mixture of hydrazine hydrate, K-acetate, and cyclohexene, heating continued 0.5 hr. -> 2-cholestene. Y 64%.—Gyclohexene is used as solvent to prevent reduction of the olefinic product. F. e. s. P. S. Wharton, S. Dunny, and L. S. Krebs, J. Org. Ghem. 29, 958 (1964). 

Miscellaneous Reactions of 2-Pyridinesulfonates. Other reactions well known for arenesulfonates are also possible with 2-pyridinesulfonates. For example, treatment of 3 -cholestanyl 2-pyridinesulfonate with sodium borohydride (DMF, 80 °C), lithium iodide (1,2-dichloroethane, 25 °C, 3 h), and LiNs (DMF, 80 °C, 4 h), gives cholestane (78%), 3a -iodocholestane (76%), and 3a-azidocholestane (63%), respectively. Treatment of 3 -cholestanyl 2-pyridinesulfonate with palladium(II) chloride (2 equiv) in DMF (80 °C, 30 min), gives 2-cholestene (80%). ... 

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