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Enantioselective Cathodic Reduction of 4‐Methylcoumarin: Dependence of Selectivity on Reaction Conditions and Investigation of the Mechanism
Author(s) -
Nielsen Merete Folmer,
Batanero Belen,
Löhl Thorsten,
Schäfer Hans J.,
Würthwein ErnstUlrich,
Fröhlich Roland
Publication year - 1997
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.19970031216
Subject(s) - chemistry , carbanion , yohimbine , protonation , electrolyte , enantioselective synthesis , catalysis , organic chemistry , electrode , ion , biochemistry , receptor , antagonist
The cathodic reduction of 4‐methylcoumarin ( 1 ) in acidic methanol/water in the presence of yohimbine leads to formation of a mixture of the hydrogenation product 4‐methyl‐3,4‐dihydrocoumarin ( 2 ), with an enantiomeric excess ( ee ) of ( R )‐ 2 of 0–67%, and the hydrodimer 3 . The relative yields of 2 and 3 and the ee of 2 depend on a number of experimental parameters such as pH, supporting electrolyte, working potential, and the concentrations of substrate and yohimbine, as demonstrated by a series of preparative‐scale experiments. In addition, a series of voltammetric 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 analytical data with the results of the preparative experiments, a single model is put forward which is in accord with the available results. The main features of the mechanistic model can be summarized as follows: 1) under acidic conditions (pH 2–3) the electroactive species is a complex between 1 and H 3 O + , the reduction of which leads to an enolic radical; 2) this radical is not reduced at the working potential but tautomerizes into the more easily reduced keto radical or dimerizes; 3) the keto radical is reduced and further protonated; 4) the function of the yohimbineH + is to catalyze the tautomerization and enantioselectively protonate the final carbanion. Additionally, we conclude that the concentration of yohimbine in the immediate vicinity of the electrode is considerably higher than its stoichiometric concentration. Quantum chemical calculations demonstrate that si protonation of the intermediate anion by yohimbineH + to give ( R )‐ 2 is energetically favored.