One-Pot Cascade Hydration-Asymmetric Transfer Hydrogenation as a Practical Strategy to Construct Chiral beta-Adrenergic Receptor Blockers
One-Pot Cascade Hydration-Asymmetric Transfer Hydrogenation as a Practical Strategy to Construct Chiral beta-Adrenergic Receptor Blockers
复制标题
一锅级联水合-不对称转移氢化作为构建手性β-肾上腺素能受体阻滞剂的实用策略
DOI：
10.1002/cctc.201500409
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发表时间：
2015
期刊：
影响因子：
4.5
通讯作者：
Liu Guohua
中科院分区：
文献类型：
--
作者：
Ye Qunqun;Cheng Tanyu;Zhao Yuxi;Zhao Junwei;Jin Ronghua;Liu Guohua
The facile construction of biologically active β‐adrenergic receptor agonists/blockers and analogues is a great fundamental and practical challenge in medical chemistry. Herein, we report a hydration–asymmetric transfer hydrogenation cascade to realize the one‐pot enantioselective transformation of aromatic haloalkynes into chiral aromatic halohydrins, which can be converted readily into chiral β‐adrenergicreceptor blockers. Such a one‐pot cascade process involves the Au‐catalyzed hydration of aryl‐substituted haloalkynes to aryl‐substituted α‐halomethyl ketones and the Ru‐catalyzed asymmetric transfer hydrogenation of aryl‐substituted α‐halomethyl ketones to aryl‐substituted 2‐haloethanols. The significant benefits of this procedure are that it provides chiral aromatic halohydrins in high yields, with excellent enantioselectivities, and a wide variety of functional groups are tolerated under mild conditions. The study described herein offers a useful approach to construct chiral β‐adrenergic blockers, which is an attractive practical organic transformation that is performed in a one‐pot manner.
