<p>Organozinc chemistry is fundamental in the synthesis of highly functionalized molecules, e.g., pharmaceuticals. However, its adaptation to continuous flow has been hindered by an intricate challenge: Reactions involving metallic zinc rely on the presence of an activated metal surface. Conventional protocols depend on chemical zinc activation and, with a few exceptions only, showcase closed processes where redosing the metal, which is consumed in the reaction, is not possible. Here, we present a continuous process that overcomes these limitations by integrating on-demand mechanical surface activation with a continuous flow reactor. A zinc rod is abraded inside a sealed chamber, delivering zinc shavings directly into the reactor under inert conditions. This “from-rod-to-reactor” approach eliminates the need for chemical pre-activation and maintains a reactive surface throughout operation. To demonstrate the viability of this new proposed setup, the Simmons-Smith synthesis, which is used to form cyclopropanes from double bonds, using activated zinc and a dihalomethane as a carbon source, is demonstrated. Using only green solvents and cinnamyl alcohol as a model substrate, we show that the process enables cyclopropanation with high conversion and yield under stable, continuous conditions. Additionally, this study could provide a scalable framework to conduct other stochiometric organometallic reactions, which rely on non-passivated metal surfaces.</p> Graphical abstract <p></p>

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From rod to reactor – a new continuous approach to the Simmons-Smith reaction

  • Daniel Moser,
  • Joscha Boehm,
  • Peter Neugebauer,
  • Dirk Kirschneck,
  • Peter Pöchlauer,
  • Heidrun Gruber-Woelfler

摘要

Organozinc chemistry is fundamental in the synthesis of highly functionalized molecules, e.g., pharmaceuticals. However, its adaptation to continuous flow has been hindered by an intricate challenge: Reactions involving metallic zinc rely on the presence of an activated metal surface. Conventional protocols depend on chemical zinc activation and, with a few exceptions only, showcase closed processes where redosing the metal, which is consumed in the reaction, is not possible. Here, we present a continuous process that overcomes these limitations by integrating on-demand mechanical surface activation with a continuous flow reactor. A zinc rod is abraded inside a sealed chamber, delivering zinc shavings directly into the reactor under inert conditions. This “from-rod-to-reactor” approach eliminates the need for chemical pre-activation and maintains a reactive surface throughout operation. To demonstrate the viability of this new proposed setup, the Simmons-Smith synthesis, which is used to form cyclopropanes from double bonds, using activated zinc and a dihalomethane as a carbon source, is demonstrated. Using only green solvents and cinnamyl alcohol as a model substrate, we show that the process enables cyclopropanation with high conversion and yield under stable, continuous conditions. Additionally, this study could provide a scalable framework to conduct other stochiometric organometallic reactions, which rely on non-passivated metal surfaces.

Graphical abstract