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Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N , N ‐Dimethylamides and Tetramethylurea in Toluene
Author(s) -
Djukanovic Dimitrije,
Heinz Benjamin,
Mandrelli Francesca,
Mostarda Serena,
Filipponi Paolo,
Martin Benjamin,
Knochel Paul
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202102805
Subject(s) - toluene , acylation , yield (engineering) , chemistry , aryl , lithium (medication) , medicinal chemistry , organic chemistry , catalysis , materials science , medicine , alkyl , metallurgy , endocrinology
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).