Enantioselective Cathodic Reduction of 4‐Methylcoumarin: Dependence of Selectivity on Reaction Conditions and Investigation of the Mechanism

Abstract

Abstract: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 0-67Y0, 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 thc 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

Ultrasound-Assisted Metal-Mediated Method for the Formation of Tetrahydro-3,3′-Disubstituted Biscoumarins

“…The reduction of coumarins is accomplished by using different metal electrodes in the presence or absence of variety of catalysts (e.g., amines, alkaloids, etc.) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. The described electrochemical reactions are applicable to both unsubstituted coumarins and coumarins substituted by electron donor groups in 3-rd or 4-th position in the lactone ring.…”

Recent Advances in Asymmetric Catalytic Electrosynthesis

“…The transformation resulted in only modest chiral induction and moderate yields, the latter due to competing dimerization of the intermediate coumarin radical. Nevertheless, the organocatalytic strategy inspired the work of other groups working in this field [81][82][83] and chiral amines have been used as additives in catalytic amounts for asymmetric reduction of various ketones, carboxylic acids and oximes as well as for reductive dehalogenation [84][85][86][87][88][89][90][91][92][93][94][95][96][97]. Electrocatalytic reductions have also been carried out using metal catalysts, including a Rh III polypyridyl complex for the hydrogenation of acetophenone with modest chiral induction [98].…”

Asymmetric Electrochemical Catalysis

“…A chiral ion pair intermediate 10 c with interaction between protonated Yohimbine and carbanion was proposed to account for the chiral induction . Later, Schäfer and co‐workers reported the enantioselectivity could be improved to 67 % by using the same alkaloid . The use of alkaloids in the asymmetric reduction through analogous conditions has been frequently reported .…”

“…[19] Later,Schäfer and co-workers reported the enantioselectivity could be improved to 67 %b yu sing the same alkaloid. [20] The use of alkaloids in the asymmetric reductiont hrough analogous conditions has been frequently reported. [21] Lu and co-workers applied chiral cinchonine 10 d in the reductive carboxylation reactiono fk etonew ith CO 2 to give the desired adduct 10 e with 36 %y ield and 27 % ee.…”