The optical yield in the alkaloid-catalyzed enantioselective 1 a. The preferred configuration of the product and the results electroreduction of 4-methylcoumarin ( l a ) was increased obtained by variation of the alkaloid structure allow us to from 17% to 47.4% by systematic variation of the electrolysis propose a model of the transition state. Furthermore, 4-pheconditions. The results are explained by an induction mecha-nylcoumarin (1 b) and 4-(trifluoromethyl)coumarin ( l c ) were nism in which the adsorbed protonated alkaloid acts as a chi-reduced with 13.2% and 8.4% ee, respectively. ral proton donor towards a prochiral carbanion derived from Methods for the enantioselective preparation of chiral products are of high interest for the synthesis of biologically active compounds for pharmaceutical or agrochemical use. This applies even more if in the conversion the chiral auxiliary is only used as catalyst. In the contributions of electrosynthesis to this issue mostly alkaloids, which are adsorbed at the electrode, are used as chiral Pioneering work in the field of alkaloid-catalyzed enantioselective electroreduction has been done by Grimshaw et al. ['I], who reduced 4-methylcoumarin (la) in the presence of different alkaloids. With sparteine or yohimbine (+)-(R)-4-methyl-3,4-dihydrocoumarin (2a) was obtained with 17% or 12% ee, respectively, besides the optically inactive hydro dimer 3a.Because of its rigid ring system, l a seemed to be a suitable prochiral precursor to investigate the alkaloid-catalyzed enantioselective electroreduction more systematically. Yohimbine was chosen as alkaloid, because of its strong adsorption atIn order to raise the optical yield and to develop a working hypothesis regarding the mechanism of the catalyzed enantioselective reduction, we varied the electrolysis conditions, the structure of the alkaloid and of the coumarin.
Resultsl a has been reduced by Grimshaw et al.r31 in a divided cell at a mercury cathode in a buffered solution (pH = 5.4) of LiCl (1.5 M) in methanol/water (4:6, v/v) as catholyte at a cathode potential of -1.8 V vs. sce with 0.07 equiv. of yohimbine as catalyst to yield 57% of 2a and 42% of 3a.Compound 2a is formed with 12% ee [eq. ( In the subsequent variation of the reaction conditions the enantioselectivity for 2a was optimized at the expense of its chemical yield. As a basis for the optimization a mechanism proposed by Talleds1 was used as working hypothesis. According to this proposal the protonated adsorbed alkaloid, here protonated yohimbine (Yoh-H+), interacts with l a [eq. (2)]. The 2e reduction of protonated l a in the complex 4 results in an ion pair 5, in which the enantioselective protonation by Yoh-H+ occurs. Subsequently, yohimbine is reprotonated to act again as chiral acid.At first the electrolysis conditions were varied. The supporting electrolyte and the counter cation of the citrate buf-
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