Continuous Flow Synthesis of β-Aminoketones as Masked Vinyl Ketone Equivalents

Herein we report the efficient synthesis of β-aminoketones via addition of a vinyl Grignard reagent into amides followed by trapping of the vinyl ketone intermediate with the magnesium-amide by-product. The reaction was successfully translated from a batch process into continuous flow mode to increase its efficiency, safety and scalability. Different set-ups were evaluated to minimize/overcome clogging issues arising from magnesium salt precipitates.

Ultimately, the resulting β-aminoketones were obtained in high yields and productivities with residence times of less than 90 seconds at elevated temperatures of 50°C. Importantly, the β-aminoketone products are valuable building blocks that can be unmasked to reactive vinyl ketones via a Cope elimination process.