Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N-Dimethylamides and Tetramethylurea in Toluene
| Autor: | Francesca Mandrelli, Paolo Filipponi, Benjamin Martin, Serena Mostarda, Benjamin Heinz, Paul Knochel, Dimitrije Djukanovic |
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| Rok vydání: | 2021 |
| Předmět: |
Methylurea Compounds
Continuous flow Aryl Communication Organic Chemistry Tetramethylurea chemistry.chemical_element General Chemistry Toluene amide Catalysis Communications Acylation chemistry.chemical_compound chemistry lithium Yield (chemistry) Amide acylation Organic chemistry continuous flow toluene Lithium |
| Zdroj: | Chemistry (Weinheim an Der Bergstrasse, Germany) |
| ISSN: | 1521-3765 |
| Popis: | 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). N,N ‐Dimethylamides for continuous flow acylations: A new acylation of (hetero)aryllithiums with polyfunctional and enolizable N,N‐dimethylamides in toluene in continuous flow was reported. The required lithium species was prepared at 25 °C from (hetero)aryl bromides and sec‐BuLi in toluene. Additionally, a new telescoped procedure, using tetramethylurea as C1‐building block, was described providing highly functionalized unsymmetrical ketones. |
| Databáze: | OpenAIRE |
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