Ketones dissolving metals, stereoselectivity

Reductions of cyclic ketones by dissolving metals are frequently highly stereoselective and these reductions have been used to obtain secondary alcohols which are difficult or impossible to prepare by metal hydride reduction. In terms of yield, the best results are usually obtained either by reductions with alkali metals (commonly Li) in liquid NH3 in the presence of proton donors or with active metals in an alcohol. Although a number of explanations have been advanced for the stereoselectivity of these reductions, they are all rationalizations with dubious predictive value." There are, however, a number of empirical generalizations which are based on a considerable body of experimental data, specifically ... 

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... 

Many ketones, especially cycloalkanones, have been reduced by metals dissolved in ammonia or alcohols in the presence of a proton donor. This method is quite useful synthetically because of its stereoselective outcome. Metals used include lithium, sodium, potassium, rubidium, magnesium, calcium, zinc, iron and more recendy, lanthanides. 

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