在甲苯中用多功能 N,N-二甲基酰胺和四甲基脲连续酰化（杂）芳基锂。
Continuous Flow Acylation of (Hetero)aryllithiums with Polyfunctional N,N-Dimethylamides and Tetramethylurea in Toluene.
机构信息
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, Haus F, 81377, Munich, Germany.
Novartis Pharma AG, Chemical Development Fabrikstraße, 4002, Basel, Switzerland.
出版信息
Chemistry. 2021 Oct 7;27(56):13977-13981. doi: 10.1002/chem.202102805. Epub 2021 Sep 9.
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).
在 25°C 下，各种芳基或杂芳基溴化物在四氢呋喃（1.0 当量）存在下与仲丁基锂（1.1 当量）在甲苯中的连续流动反应在 40 秒内提供了相应的芳基锂，这些芳基锂在-20°C 下与各种功能化的 N,N-二甲基酰胺（包括易于烯醇化的酰胺）在 27 秒内酰化，以 48-90%的产率（36 个实例）生成高度官能化的酮。该方法非常适合制备α-手性酮，如萘普生和布洛芬衍生的酮，ee 值为 99%。两种不同的有机锂金属一锅分步双加成到 1,1,3,3-四甲基脲（TMU）中，以 69-79%的产率（9 个实例）提供了不对称酮。
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