Memory of chirality in a room temperature flow electrochemical reactor

Abstract

Chiral compounds have become of great interest to the pharmaceutical industry as they possess various biological activities. Concurrently, the concept of “memory of chirality” has been proven as a powerful tool in asymmetric synthesis, while flow chemistry has begun its rise as a new enabling technology to add to the ever increasing arsenal of techniques available to the modern day chemist. Here, we have employed a new simple electrochemical microreactor design to oxidise an l-proline derivative at room temperature in continuous flow. Compared to batch, organic electrosynthesis via microflow reactors are advantageous because they allow shorter reaction times, optimization and scale up, safer working environments, and high selectivities (e.g. reduce overoxidation). Flow electrochemical reactors also provide high surface-to-volume ratios and impart the possibility of excluding the supporting electrolyte due to a very short interelectrode distance. By the comparison of Hofer Moest type electrochemical oxidations at room temperature in batch and flow, we conclude that continuous flow electrolysis is superior to batch, producing a good yield (71%) and a higher enantiomeric excess (64%). These results show that continuous flow has the potential to act as a new enabling technology for asymmetric synthesis to replace some aspects of conventional batch electrochemical processes.

Iodine-mediated electrocatalysis assist Annulation/cyclization via Intramolecular Benzylic C–H Amination: Batch vs Flow Electrochemistry

“…However, the use of electrochemistry for the synthesis of these compounds has been shown to be very efficient and this could be more promising in future using flow electrochemical microreactor. 11…”

“…[5][6][7][8][9] Now, many of challenging chemical transformations and new bonds formation are possible under ambient and environmentally benign conditions. 10,11 Due to the great importance, the study of new C-N bonds for the synthesis of pyrrolidines and other heterocyclic structures has been explored for many decades, in addition, the development of a new methodology to obtain highly selective reactions is one of the most important areas in synthetic organic chemistry. Electrochemistry in general is the study of chemical reactions that occur at the interface of an electrode, usually a solid metal or a semiconductor, and an ionic conductor, the electrolyte.…”

Renewable Electricity Enables Green Routes to Fine Chemicals and Pharmaceuticals

“…A novel yet simple electrochemical microreactor model was employed by Hardwick and co-workers to oxidise the derivatives of L-proline with subsequent decarboxylation taking place in flow a microreactor at room temperature. [309] The reaction is initiated with electrolysis facilitating the decarboxylation reaction to form a radical species. Nacyliminium ion is formed by this step, the positive charge of which is localised about the heteroatom.…”

Organic synthesis via Kolbe and related non-Kolbe electrolysis: an enabling electro-strategy

“…electrochemical organic transformations using carboxylic acids derivatives [17][18][19][20] were mainly focused on derivatization from aromatic esters and selective bond cleavage. However, there has not been addressed the electrochemical transformations resulting via "memory of chirality" [27][28][29][30][31] or recent developments. Herein, we discussed recent several examples of electrochemical decarboxylation (ED) and its applications to drive value-added transformations under mild, clean and sustainable conditions and also addressed related mechanistic aspects.…”

“…On the basis of this concept, recently we developed an efficient example of memory of chirality method via non-Kolbe electrolysis to provide enantiomerically N, O-acetal derivative 19 via the electrochemical transformation of the corresponding substrate 18 (scheme 13) 31 . The direct oxidation of proline-based substrate 18 provides a decarboxylation reaction and affords a radical cation iminium ion A, which is then trapped by MeO -, resulting in the desired product 19 via the mechanism illustrated in scheme 14.…”