Amino acid derivatives undergon on-Kolbe electrolysis to afford enantiomerically enriched a-alkoxyamino derivatives through intermediate chiralc arbenium ions. The products contain N,O-acetals which are important structural motifs foundi nb ioactive natural products.T he reactioni sp erformedi nacontinuous flow electrochemical reactor coupled to a2 D-HPLC for immediate online analysis. This allowed af ast screening of temperature, electrode material, current, flow-rate andc oncentration in aD oE approach. The combination with online HPLC demonstrates that also stereoselective reactions can benefit from ah ugely acceleratedo ptimisation by combining flow electrochemistry with multidimensional analysis.Scheme1.Electrochemical oxidation of N-arylcarbonylated amino acid derivativest oc hiral alkoxylated amides in aflow electro-microreactor.Scheme2.First example of 'memory of chirality' on N-aryl serine derivatives 1 reported by Matsumuraetal. [19] [a

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.

<p>Many 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. Flow performed in microreactors offers up a number of benefits allowing reactions to be performed in a more convenient and safer manner, and even allow electrochemical reactions to take place without a supporting electrolyte due to a very short interelectrode distance. By the comparison of electrochemical oxidations in batch and flow we have found that continuous flow is able to outperform its batch counterpart, producing a good yield (71%) and a better enantiomeric excess (64%) than batch with a 98% conversion. We have, therefore, provided evidence that continuous flow chemistry has the potential to act as a new enabling technology to replace some aspects of conventional batch processes. </p>

<p>Many 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. Electrochemical methods are inherently green and environmentally benign. However, organic electrosynthesis via microflow reactor has number of advantages such as fast reaction’s time, optimization and scale up, safer environment, high selectivities and reduce chances of overoxidation. Flow electrochemical reactor provides high surface-to-volume ratio and reactions are possible to perform in the reactor without a 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 have achieved that continuous flow electrolysis is better than batch electrolysis, producing a good yield (71%) and a better enantiomeric excess (64%). These results show that continuous flow electrolysis has the potential to act as a new enabling technology for asymmetric synthesis to replace some aspects of conventional batch electrochemical processes. </p>

<p>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. </p>