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Updated: Oct 24, 2025
A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N-Dimethylamides and Tetramethylurea in
Dimitrije Djukanovic1, Benjamin Heinz1, Francesca Mandrelli2
1Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, Haus F, 81377, Munich, Germany.
Abstract:
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).
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