Dissolving metals stereoselectivity

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

Electrochemical reduction of camphor-and norcamphoroxime at a Hg cathode proceeds with a high degree of stereoselectivity to give products of opposite stereochemistry to those formed in the dissolving metal (Na-alcohol) reduction of the oximes. The electrolyses are proposed to proceed by a kinetically controlled attack by the electrode on each oxime from the less hindered side (Fig. 62) [348]. In contrast, the corresponding N-phenyl imines yield products of the same stereochemistry as those isolated from a dissolving metal reduction. Cyclic voltammetry and polarographic data point to RH and intermediates in this case that are proto-nated from the least hindered side [349]. 

A. M. El-Khawaga, H. M. R. Hoffmann, Formation of C-H Bonds by the Reduction of C=C Double Bonds and of Carbonyl Groups with Metals ( Dissolving Metal Reduction ), in Stereoselective Synthesis (Houben-Weyl) 4th ed., 1996, (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), 1996, Vol. E21 (Workbench Edition), 7, 3967—3987, Georg Thieme Verlag, Stuttgart. 

Monti and his co-workers have successfully demonstrated not only the efficiency of intramolecular ketocarbene capture in the production of tricyclo[3.3.0.02-8 ]-octan-3-one (27), but also the marked stereoselectivity of its dissolving metal cleavage and ring opening under acidic conditions (Scheme 7).ss Prevailing stereoelec-tronic and thermodynamic factors favor predominant conversion to bicyclo[3.3.0]-octyl end products. 

An Algox Pharmaceutical group reported a preparation of MNA capitalizing on a C5 + C5 strategy, and based on the alkylation of bromovaleric add (S2) with the lithium anion of 3-methyl-l-butyne (S3), followed by stereoselective reduction of 8-methyl-6-noninoic acid (S4) to ( )-MNA by dissolving-metal reduction. 

Dissolving metal reduction of a triple bond with Na in NH3 Is a stereoselective reaction because it forms a trans product exclusively. 

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... 

This chapter is devoted to the discussion of the reduction of carbon-carbon double and triple bonds by noncatalytic methods, These methods include reductions by diimide, by dissolving metals in the presence or absence of proton donors, by low-valent metal ions, by metal hydride-metal halide combinations and by so-called ionic hydrogenation procedures. Of these widely diverse methods of reduction of carbon-carbon double and triple bonds, the reduction by diimide appears to be the most versatile. The reduction of carbon-carbon double and triple bonds by diimide occurs with complete stereoselectivity and stereo-specificity, and can be effected in the presence of a variety of other, very chemically reactive functional... 

---