Tech-Enhanced Synthesis: Exploring the Synergy between Organic Chemistry and Technology

Abstract

Recent years have witnessed growing interest in integrating enabling technologies into synthetic organic chemistry to address long-standing challenges in reproducibility, sustainability, and scalability. This perspective showcases how modern tools, ranging from continuous-flow reactors and electrochemical cells to photochemical technologies, biocatalysis, mechanochemistry, and self-driving laboratories, are reshaping the way chemists design, perform, and optimize reactions. Through selected case studies, we highlight how these technologies not only solve specific reactivity and process issues but also open new avenues for reactivity discovery and chemical innovation. Rather than viewing technology as a complication, we advocate for its adoption as a natural extension of synthetic creativity, capable of enhancing safety, reducing waste, and expanding accessible chemical space. Our aim is to inspire broader implementation and interdisciplinary training to equip the next generation of chemists with the tools to rethink how synthesis is performed in the 21st century.

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Functionalization of gaseous alkanes in continuous flow.

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Rapid SuFEx ligation of small molecules, peptides, and proteins in continuous flow.

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Generation and use of trifluoromethyl-heteroatom anions in continuous flow.

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Multistep synthesis in continuous flow.

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High-Throughput Experimentation (HTE) as enabling technology in photocatalysis.

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Enabling technologies for the efficient and sustainable scale-up of photocatalysis.

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Photochemical manufacturing process in continuous flow. Reproduced from ref with permission from American Chemical Society.

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Microfluidic redox-neutral electrochemical (mRN-eChem) platform.

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Rapid alternating polarity (rAP) in electro-organic synthesis.

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Light-harvesting microelectronic devices for wireless electrosynthesis. Reproduced from ref with permission from Springer Nature.

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RoboChem: multipurpose robotic platform for the autonomous optimization and intensification of photocatalytic reactions. Reproduced from ref with permission from The American Association for the Advancement of Science.

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Network of SDLs coordinated by a cloud hub for new OSL materials. Reproduced from ref with permission from The American Association for the Advancement of Science.

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Repurposing chemical waste via computer-aided synthesis planning.

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Application of engineered biocatalytic cascades to streamline the synthesis of Islatravir (66).

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Immobilization of transaminase enzymes on resin. Reproduced from ref with permission from American Chemical Society.

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Non-natural enzymes via ncAA incorporation.

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Mechanochemistry promotes the activation of zerovalent metals (Mg, Zn, Li): applications to the direct metalation of alkyl halides and Birch-type reduction. Reproduced from ref with permission from Springer Nature.

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Mechanoredox ball milling. Reproduced from ref with permission from The American Association for the Advancement of Science.

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Upscaling of mechanochemistry in continuous flow. Reproduced from ref with permission from Wiley-VCH GmbH.