Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N‐Dimethylamides and Tetramethylurea in Toluene

The continuous flow reaction of various aryl or heteroaryl bromides in toluene in the presence of THF (1.0 equiv) with sec‐BuLi (1.1 equiv) provided at 25 °C within 40 sec the corresponding aryllithiums which were acylated with various functionalized N,N‐dimethylamides including easily enolizable amides at −20 °C within 27 sec, producing highly functionalized ketones in 48–90 % yield (36 examples). This method was well suited for the preparation of α‐chiral ketones such as naproxene and ibuprofen derived ketones with 99 % ee. A one‐pot stepwise bis‐addition of two different lithium organometallics to 1,1,3,3‐tetramethyurea (TMU) provided unsymmetrical ketones in 69–79 % yield (9 examples).