Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N-Dimethylamides and Tetramethylurea in Toluene
Martin, Benjamin, Filipponi, Paolo, Mostarda, Serena, Mandrelli, Francesca, Knochel, Paul, Heinz, Benjamin and Djukanovic, Dimitrije (2021) Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N-Dimethylamides and Tetramethylurea in Toluene. Chemistry—A European Journal, 27. pp. 1-6. ISSN 15213765
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).
Item Type: | Article |
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Keywords: | acylation amide continuous flow lithium Toluene |
Date Deposited: | 29 Sep 2021 00:45 |
Last Modified: | 29 Sep 2021 00:45 |
URI: | https://oak.novartis.com/id/eprint/45148 |