Clemmensen Reduction Cholestane

Submitted by Shosuke Yamamura,1 Masaaki Toda,2 and Yoshimasa Hirata2 

A 500-ml. four-necked round-bottomed flask (Note 1) equipped with a sealed mechanical stirrer (Note 2), a gas inlet tube, a low-temperature thermometer, and a calcium chloride 

A standard three-necked flask fitted with a Y-tube may be used. 

Approximately one bubble per second can be spot-checked periodically by connecting the calcium chloride tube to an oil-filled bubble counter. 

139 (1943) single spot on t.l.c. with the system described in Note 11. 

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W-Methylpiperidine, 52, 127 3-Methyl-3-sulfolene, in Diels-Alder reaction, 50, 48 MODIFIED CLEMMENSEN REDUCTION CHOLESTANE, 53, 86... 

Two novel complex hydrides are likely to find applications in steroid chemistry lithium perhydro-9b-boraphen yl hydride affords unusually high proportions of axial alcohols in model compounds sodium bis(methoxyethoxy)aluminium dihydride, Na (MeOCH2CH20)JAlH2, a very safe and convenient substitute for lithium aluminium hydride, readily reduces not only ketones but also acids, nitro-compounds, oximes, amides, lactones, etc. An improved procedure for Clemmensen reduction of steroid ketones involves saturating an ethereal solution with hydrogen chloride while stirring with zinc. 5a-Cholestane was obtained from the 3-one in 89% yield. ... 

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). 

In conjugated carbonyl systems, the usual Clemmensen conditions may give rise to reduction and isomerization of the C=C double bond. When treated with zinc powder in acetic anhydride saturated with hydrogen chloride, cholest-l-en-3-one (6 Scheme 5) is converted to a mixture of cholestane (7 30-32%), 3-acetoxycholest-2-ene (8 10-24%) and cholestan-3-one (9 30 0%). 

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