Sodium imide carbonyl reduction with

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

More symmetrical imides may still be regioselectively reduced. In the case of geminally disub-stituted succinimidcs the stcrically more hindered carbonyl function is preferentially reduced with sodium borohydride. The regioselectivity ranges from 79 21 for the dimethyl derivative to > 95 5 for the diphenyl derivative29. For monosubstituted succinimides the selectivity of the reduction is low29, unless the substituent is an acetoxy group35-36. 

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