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One‐Pot Cascade Hydration–Asymmetric Transfer Hydrogenation as a Practical Strategy to Construct Chiral β‐Adrenergic Receptor Blockers
Author(s) -
Ye Qunqun,
Cheng Tanyu,
Zhao Yuxi,
Zhao Junwei,
Jin Ronghua,
Liu Guohua
Publication year - 2015
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201500409
Subject(s) - enantioselective synthesis , aryl , chemistry , transfer hydrogenation , cascade , combinatorial chemistry , catalysis , transformation (genetics) , organic chemistry , biochemistry , alkyl , chromatography , ruthenium , gene
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.