Organocatalyzed Decarboxylative Trichloromethylation of Morita-Baylis-Hillman Adducts in Batch and Continuous Flow

Two protocols for the organocatalyzed decarboxylative trichloromethylation of Morita-Baylis-Hillman (MBH) substrates have been developed. Applying sodium trichloroacetate, as the trichloromethyl anion precursor, in combination with an organocatalyst and acetylated MBH-alcohols, the desired trichloromethylated products were obtained in good yields at room temperature in batch. The method was next extrapolated into a two-step continuous flow protocol, starting directly from the MBH alcohols, in combination with tributylamine acting both as base and catalyst. The flow process proved superior to the batch approach, reducing the reaction time from 16 hours to only 20 minutes, with increased yields for all investigated entries. Two examples were also taken to scale-up in flow producing more than 10 grams of both trichloromethylated targets. Finally, substitution of the organocatalyst to (DHQ)₂ PHAL or (DHQD)₂ PHAL induced chiral transfer to the generated stereocenter in the reaction attaining selectivities with nearly 90 % ee.