Basic Anion-Exchange Resin-Catalyzed Aldol Condensation of Aromatic Ketones with Aldehydes in Continuous Flow
Basic Anion-Exchange Resin-Catalyzed Aldol Condensation of Aromatic Ketones with Aldehydes in Continuous Flow
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DOI：
10.1021/acs.oprd.9b00048
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
Kobayashi, Shu
中科院分区：
文献类型：
--
作者：
Laroche, Benjamin;Saito, Yuki;Kobayashi, Shu
采用市售强碱性阴离子交换树脂（A26）作为催化剂，在连续流动条件下研究了芳香酮与醛缩反应的一般方法。该过程除了显示出广泛的底物范围外，还使用具有良好收率的准化学计量比的起始试剂在温和条件下促进碳-碳键的形成，从而形成有限数量的废物，并允许该过程应用于顺序流系统。首个完全多相催化的两步流合成多奈哌齐的概念验证得到了发展，多奈哌齐是一种重磅商业抗阿尔茨海默病药物。
A general method for the aldol condensation of aromatic ketones with aldehydes was developed under continuous-flow conditions using a commercially available, strongly basic anion-exchange resin (A26) as catalyst. This procedure, in addition to exhibiting a wide substrate scope, promoted carbon-carbon bond formation under mild conditions using a quasi-stoichiometric ratio of starting reagents with good to excellent yields, thereby forming a limited amount of waste and allowing the process to be applied to sequential-flow systems. A proof of concept was developed in the first fully heterogeneously catalyzed two-step flow synthesis of donepezil, which is a blockbuster commercial anti-Alzheimer's drug.