Continuous-Flow Synthesis of Primary Vinylarenes via Inline Grignard Reagent Formation and Peterson Olefination.

Abstract

Primary vinylarenes are important monomers for the production of materials, which in our case are ion exchange membranes for electrolyzers. Given the high cost of certain vinylarenes but the relative affordability of their aldehyde precursors, we explored their synthesis using flow chemistry to enable facile and safe scale-up. While a soluble, methanolic Wittig reaction found limited success, an alternative approach involving Peterson olefination was high-yielding. This required (trimethylsilyl)methyl Grignard reagent, which was generated in flow using a magnesium-filled column. Thus, 2-vinylthiophene was obtained in 93% yield at 37 g scale, and the route was applicable to other nonpolar arenes. For polar arenes, precipitation at the oxymagnesium chloride stage and inefficient elimination were observed, but these challenges could be mitigated by employing (phenyldimethylsilyl)methyl Grignard reagent instead and stronger acid at a higher temperature for the elimination.