ENANTIOSELECTIVE CATHODIC REDUCTION OF 4-METHYLCOUMARIN - DEPENDENCE OF SELECTIVITY ON REACTION CONDITIONS AND INVESTIGATION OF THE MECHANISM

The cathodic reduction of 4-methylcoumarin (1) in acidic methanol/wate r in the presence of yohimbine leads to formation of a mixture of the hydrogenation product 4-methyl-3,4-dihydrocoumarin (2), with an enanti omeric excess tee) of (R)-2 of 0-67%, and the hydrodimer 3. The relati ve yields of 2 and 3 and the re of 2 depend on a number of experimenta l parameters such as pH, supporting electrolyte, working potential, an d the concentrations of substrate and yohimbine, as demonstrated by a series of preparative-scale experiments, In addition, a series of volt ammetric and kinetic measurements were carried out to investigate the influence of the individual experimental parameters, Three mechanistic possibilities have been examined, and by combination of the analytica l data with the results of the preparative experiments, a single model is put forward which is in accord with the available results. The mai n features of the mechanistic model can be summarized as follows: 1) u nder acidic conditions (pH 2-3) the electroactive species is a complex between 1 and H3O+, the reduction of which leads to an enolic radical ; 2) this radical is not reduced at the working potential but tautomer izes into the more easily reduced keto radical or dimerizes; 3) the ke to radical is reduced and further protonated; 4) the function of the y ohimbineH(+) is to catalyze the tautomerization and enantioselectively protonate the final carbanion. Additionally, we conclude that the con centration of yohimbine in the immediate vicinity of the electrode is considerably higher than its stoichiometric concentration. Quantum che mical calculations demonstrate that si protonation of the intermediate anion by yohimbineH(+) to give (R)-2 is energetically favored.