Harnessing [1,4], [1,5], and [1,6] Anionic Fries-type Rearrangements by Reaction-Time Control in Flow

A series of anionic Fries-type rearrangements of carbamoyl-substituted aryllithium intermediates were controlled by using flow microreactor systems. For the [1,4] and [1,5] rearrangements, the aryllithium intermediate formed before carbamoyl migration and the lithium alkoxide formed after carbamoyl migration can be selectively subjected to subsequent reactions with electrophiles by precisely controlling the residence time and temperature (-25 to -50 degrees C). In contrast, the [1,6] rearrangement is rather slow even at -25 degrees C. The absence of crossover products indicates the intramolecular nature of the carbamoyl group migration.