Steroids, 12-keto dissolving metals

Dissolving metal reductions remain the method of choice, and are frequently the only viable method, for the reduction of sterically hindered cyclohexanones to equatorial alcohols. In the early 1950s it was found that reduction of 11-keto steroids using either Na-propan-l-oP or Li-NHs-dioxane-ethanol gave good yields of the equatorial I la-alcohol. 11-Keto steroids, such as androstan-11-one (29 equation 12) have two axial methyl groups in a 1,3-relationship to the carbonyl group and afford exclusively the axial 11 P-ol (30) on reduction with metal hydrides. 

Although they have apparently not been studied in detail, dissolving metal reductions of 1 -keto steroids appear similar to those of the 12-keto steroids. In one report, cholestan-l-one (49 equation 17) on reduction with Na in either ethanol or I-pentanol gave the axial alcohol, cholestan-la-ol (50), as the major reduction product in unspecified yield. The equatorial ip-ol was detected by TLC, but could not be isolated. 

The reductions of 1- and 12-keto steroids and their 1-decalone derivatives graphically illustrate the fact that dissolving metal reductions of ketones do not necessarily afford the more stable of a pair of epimeric alcohols. As a corollary, while the reduction of cyclic ketones is a synthetically useful procedure for the stereoselective preparation of secondary alcohols, it cannot be assumed that the thermodynamically stable alcohol will be the product which is obtained stereoselectively. 

The reductions of two steroidal ketones, androstan-l7-one (63) and androst-5-en-16-one (64) under various conditions have been studied in some detail. In the case of 17-ketone (63) the -ol (65) is the stable epimer and for the 16-ol (66), the a-isomer is more stable. Dissolving metal reductions of both ketones in the presence of proton donors gave the more stable alcohol as the major product however, reduction of 17-keto steroid (63) is considerably more stereoselective as noted in Table 2. Although pina-cols are not usually obtained in dissolving metal reductions carried out in the presence of proton donors, ketone (63) gave from 6 to 34% of dimeric products under these conditions (Li, 6% Na, 34% K, 13%). 5... 

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