ENANTIOSELECTIVE REDUCTION OF 3-METHYLINDEN-1-ONE IN THE PRESENCE OF CHIRAL CATALYSTS

摘要

A mechanistic scheme for the enantioselective cathodic reduction of 3-methyl-inden-1-one (1) has been developed, which is supported by preparative scale electrolyses and cyclovoltammetry. Based on this mechanism nonracemic catalysts could be designed with a much simpler structure than strychnine. Enantiopure compounds are needed as Pharmaceuticals. They can be prepared by diasteroselective or enantioselective synthesis. The latter method is more attractive as only one step is needed to introduce the enantioenriched stereogenic center. Whilst these reactions are highly advanced in conversions that involve chiral transition metal complexes as recently rewarded by the Nobel prize to Knowles, Sharpless and Noyori, the method is much less developed for reactions involving reactive intermediates as encountered in direct electrosynthesis. Enantioselective cathodic reduction with yohimbine as catalyst has been reported for 4-methylcoumarine. By optimization of the reaction conditions an enantioselectivity of 63 % ee for (S)-4-methyldihydrocoumarine has been achieved and a mechanism been proposed. For a further mechanistic investigation the reduction of 3-methylinden-1-one (1) appeared to be more favorable because of the less negative reduction potential of 1, which leads to less interference with the reduction of the suppporting electrolyte.