Renewable Electricity Enables Green Routes to Fine Chemicals and Pharmaceuticals.

Syntheses of chemicals using renewable electricity and when generating high atom economies are considered green and sustainable processes. In the present state of affairs, electrochemical manufacturing of fine chemicals and pharmaceuticals is not as common place as it could be and therefore, merits more attention. There is also a need to turn attention toward the electrochemical synthesis of valuable chemicals from recyclable greenhouse gases that can accelerate the process of circular economy. CO2 emissions are the major contributor to human-induced global warming. CO2 conversion into chemicals is a valuable application of its utilisation and will contribute to circular economy while maintaining environmental sustainability. Herein, we present an overview of electro-carboxylation, including mechanistic aspects, which forms carboxylic acids using molecular carbon dioxide. We also discuss atom economies of electrochemical fluorination, methoxylation and amide formation reactions.

Memory of chirality in a room temperature flow electrochemical reactor.

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.

Interfacial Photoelectrochemical Catalysis: Solar-Induced Green Synthesis of Organic Molecules.

Many oxidation and reduction reactions in conventional organic synthesis rely on harsh conditions, toxic or corrosive substances, and environmentally damaging chemicals. In addition, competing reactions may take place, some of which produce hazardous waste products and, therefore, reaction selectivity suffers. To overcome such synthetic drawbacks, an enormous effort is being devoted to find alternative processes that operate much more efficiently, requiring milder conditions to contribute to a greener economy and provide urgently needed new pathways with enhanced selectivity. Fortunately, there is a strategy that has attracted global interest from multiple disciplines that involves the use of sunlight to perform artificial photosynthesis, in which a photoelectrochemical cell splits water into hydrogen fuel, reduces CO2 into "solar" fuels, and more recently, convert organic chemicals into higher value products. Recently, photoanode and photocathode materials have emerged as useful tools to perform organic oxidations and reductions for the synthesis of important molecules, other than just hydrogen or oxygen. Whereas many studies have focused on the degradation of unwanted and dangerous chemicals, solar-induced organic transformations have attracted much less attention. This Minireview summarizes some of latest research efforts in using photoelectrochemical cells to facilitate organic oxidation and reduction reactions to avoid valuable substances while avoiding toxic reagents and expensive precious metal catalysts. Future developments that will enable such technologies to broaden their scope are also considered.

Digitising chemical synthesis in automated and robotic flow.

Continuous flow chemical synthesis is already known to have many attributes that give it superiority over batch processes in several respects. To expand these advantages with those from automation will only drive such enabling technologies further into the faster producing, more efficient 21st century chemical world. In this report we present several examples of algorithmic chemical search, along with flow platforms that link hardware and digital chemical operations on software. This enables organic syntheses to be automatically carried out and optimised with as little human intervention as possible. By applying such enabling technologies to the production of small organic molecules and pharmaceutical compounds in end-to-end multistep processes, a range of reaction types can be accessed and, thus, the flexibility of these single, compact flow designs may be revealed. Automated systems can allow several reactions to take place on the same setup, enabling direct comparison of reactions under different conditions. Moreover, the production of new and known target compounds can be made faster and more efficient, the recipes of which can then be stored as digital files. Some of the automating software has employed machine-powered learning to assist the chemist in developing intelligent algorithms and artificial intelligence (AI) driven synthetic route planning. This ultimately produces a continuous flow platform that can design its own viable pathway to a particular molecule and then carry it out on its own, allowing the chemists, at the same time, to apply their expertise to other pressing challenges in their fields.

Memory of Chirality in Flow Electrochemistry: Fast Optimisation with DoE and Online 2D-HPLC.

Amino acid derivatives undergo non-Kolbe electrolysis to afford enantiomerically enriched α-alkoxyamino derivatives through intermediate chiral carbenium ions. The products contain N,O-acetals which are important structural motifs found in bioactive natural products. The reaction is performed in a continuous flow electrochemical reactor coupled to a 2D-HPLC for immediate online analysis. This allowed a fast screening of temperature, electrode material, current, flow-rate and concentration in a DoE approach. The combination with online HPLC demonstrates that also stereoselective reactions can benefit from a hugely accelerated optimisation by combining flow electrochemistry with multidimensional analysis.

Memory of Chirality as a Prominent Pathway for the Synthesis of Natural Products through Chiral Intermediates.

The ability of a chiral molecule to be able to transform from one structure to another, whilst remembering its original molecular information by means of an appropriate transition state is an abstract notion that may very well play a key role in important synthetic processes, and has thus attracted a considerable amount of attention among the chemistry community. Here, we have highlighted this concept of "memory of chirality" (MOC) and extended it beyond the case of a simple molecule to larger and more complex natural products. Updated approaches that have recently been elucidated to obtain these asymmetric natural products are described, some of which may, until now, have been overcomplicated or overlooked.

Advances in electro- and sono-microreactors for chemical synthesis.

The anatomy of electrochemical flow microreactors is important to safely perform chemical reactions in order to obtain pure and high yielding substances in a controlled and precise way that excludes the use of supporting electrolytes. Flow microreactors are advantageous in handling unstable intermediates compared to batch techniques and have efficient heat/mass transfer. Electrode nature (cathode and anode) and their available exposed surface area to the reaction mixture, parameters of the spacer, flow rate and direction greatly affects the efficiency of the electrochemical reactor. Solid formation during reactions may result in a blockage and consequently decrease the overall yield, thus limiting the use of microreactors in the field of electrosynthesis. This problem could certainly be overcome by application of ultrasound to break the solids for consistent flow. In this review, we discuss in detail the aforementioned issues, the advances in microreactor technology for chemical synthesis, with possible application of sonochemistry to deal with solid formations. Various examples of flow methods for electrosynthesis through microreactors have been explained in this review, which would definitely help to meet future demands for efficient synthesis and production of various pharmaceuticals and fine chemicals.