Synthesis of fluorinated donepezil by palladiumcatalyzed decarboxylative allylation of a-fluoro-β-keto ester with tri-substituted heterocyclic alkene and the self-disproportionation of its enantiomers
Synthesis of fluorinated donepezil by palladiumcatalyzed decarboxylative allylation of a-fluoro-β-keto ester with tri-substituted heterocyclic alkene and the self-disproportionation of its enantiomers
复制标题
钯催化α-氟-β-酮酯与三取代杂环烯烃脱羧烯丙基化合成氟化多奈哌齐及其对映体的自歧化
DOI：
10.1039/c6ra21253k
复制
发表时间：
2016
期刊：
影响因子：
3.9
通讯作者：
Norio Shibata
中科院分区：
文献类型：
--
作者：
Mayaka Maeno;Hiroya Kondo;Etsuko Tokunaga;Norio Shibata
氟多奈哌齐是一种很有前途的治疗阿尔茨海默病的新药物，其合成是通过钯催化的具有三取代杂环烯烃体系的烯丙基酯的脱羧烯丙基化反应（DcA）作为关键步骤实现的。这一策略与标题化合物的专利方法非常不同，该方法已成功地扩展到氟化多奈哌齐的第一个催化不对称合成。氟代多奈哌齐在对映体的自异构化中表现出明显的量级。
The synthesis of fluorinated donepezil, a promising new therapeutic agent for Alzheimer's disease, was achieved by the palladium-catalyzed decarboxylative allylation (DcA) of an allylic ester having a tri-substituted heterocyclic alkene system as a key step. This strategy is very different from a patented method for the title compound which was successfully extended to the first catalytic asymmetric synthesis of fluorinated donepezil. Fluorinated donepezil showed a noticeable magnitude in the self-disproportionation of enantiomers.