Self-assembled monolayer protection of chiral-imprinted mesoporous platinum electrodes for highly enantioselective synthesis

In modern chemistry, chiral (electro)catalysis is a powerful strategy to produce enantiomerically pure compounds (EPC). However, it still struggles with uncontrollable stereochemistry due to side reactions, eventually producing a racemic mixture. To overcome this important challenge, a well-controlled design of chiral catalyst materials is mandatory to produce enantiomers with acceptable purity. In this context, we propose the synergetic combination of two strategies, namely the elaboration of mesoporous Pt films, imprinted with chiral recognition sites, together with the spatially controlled formation of a self-assembled monolayer. Chiral imprinted metals have been previously suggested as electrode materials for enantioselective recognition, separation and synthesis. However, the outermost surface of such electrodes is lacking chiral information and thus leads to unspecific reactions. Functionalising selectively this part of the electrode with a monolayer of organosulfur ligands allows an almost total suppression of undesired side reactions and thus leads to a boost of enantiomeric excess to values of over 90% when using these surfaces in the frame of enantioselective electrosynthesis. In addition, this strategy also decreases the total reaction time by one order of magnitude. The study therefore opens up promising perspectives for the development of heterogeneous enantioselective electrocatalysis strategies.


Asymmetric electrosynthesis of 1-(4-bromophenyl) ethanol (4-Br-PE):
Enantioselective synthesis of 4-Br-PE was performed in the experimental set-up as shown in Fig. S13 by the optimized potentiostatic synthesis via reduction of 4bromoacetophenone (4-Br-AP) at -0.50 V for 13 h in a stirred solution of 5 mM 4-Br-AP dissolved in 7 mL of a mixture of 10/90 (v/v) isopropyl alcohol with 1 M NH 4 Cl as supporting electrolyte with a solution pH of 5.0. The product mixtures were extracted with heptane and analyzed by a high-performance liquid chromatography (HPLC), performed on a Shimadzu LC-2030C3D equipped with a CHIRALPAK IB (250 × 4.6 mm inner diameter) column and a photodiode array (PDA) detector at 220 nm, using a mobile phase containing 5% isopropyl alcohol and 95% heptane (v/v) at a flow rate of 0.5 mL min -1 .

Reusability tests:
To study the reusability of thiol-coated electrodes, the catalyst surface is regenerated by rinsing several times and immersing it overnight in MQ water. Then, the electrode was directly used for the next catalytic run, following the same protocol of enantioselective synthesis as previously. The product solution was analyzed by HPLC (Shimadzu LC-2030C3D) with a CHIRALPAK IB column (250 × 4.6 mm inner diameter) and a PDA detector at 215 nm. A mixture of 7.5 isopropyl alcohol/92.5 heptane (v/v) was used as mobile phase, flowing at a rate of 0.5 mL min -1 . Repeating the µCP modification allows regenerating a protected electrode surface.

Calculation of operational parameters:
Parameters which express the performance of the different types of electrodes used in this study are: (i) Conversion, (ii) Enantiomeric excess (%ee), (iii) Standard error of the mean of the enantiomeric excess (s.e.m.) and (iv) Efficiency of the catalyst.
(i) The proportion of overall conversion after electroreduction is obtained from a linear relationship, y = 0.0019x (R 2 = 0.9969), of the calibration curve based on HPLC measurements of the peak area ratios. Solutions of acetophenone (AP) and 1-phenylethanol (PE) were mixed to prepare the standard solutions, representating 0, 5, 10, 15 and 20% conversion of AP to PE. Then, the standard solutions were analyzed by HPLC, the peak areas of AP and PE were integrated with Lab Solution software, and the obtained results were used to calculate the ratios of peak areas of PE and APE. This calibration curve can be applied to estimate the overall conversion for the all the experiments listed in Table S1.
(ii) The enantiomeric excess (%ee) was obtained by using equation (1) in order to evaluate the product selectivity of the catalytic electroreduction: (1) where (R)PE and (S)PE are the integrated areas of the (R)PE and (S)PE peaks in the HPLC chromatograms, respectively.
(iii) The standard error of the mean of the enantiomeric excess (s.e.m.) is defined by equation (2): (2) where is the standard deviation, and is a number of experiments.
(iv) The production rate of chiral compound in the present study is defined in terms of the amount of a selectively produced enantiomer (mol desired chiral product ) with respect to the electrochemically active surface area (ESA) and the global reaction time (t) as shown by equation (3).
The ESA value can be obtained from the hydrogen adsorption/desorption region in the cyclic voltammograms of the electrodes measured in H 2 SO 4 as illustrated in Fig. S6, and the obtained information is summarized in Table S1.