含氟芳香酮参与的催化不对称曼尼希反应：高效合成手性β-氟胺
Catalytic Asymmetric Mannich Reactions with Fluorinated Aromatic Ketones: Efficient Access to Chiral β-Fluoroamines.
作者信息
Trost Barry M, Saget Tanguy, Lerchen Andreas, Hung Chao-I Joey
机构信息
Department of Chemistry, Stanford University, Stanford, CA 94305-5080 (USA).
出版信息
Angew Chem Int Ed Engl. 2016 Jan 11;55(2):781-4. doi: 10.1002/anie.201509719. Epub 2015 Nov 26.
Abstract
Reported herein is a Zn/Prophenol-catalyzed Mannich reaction using fluorinated aromatic ketones as nucleophilic partners for the direct enantio- and diastereoselective construction of β-fluoroamine motifs featuring a fluorinated tetrasubstituted carbon. The reaction can be run on a gram scale with a low catalyst loading without impacting its efficiency. Moreover, a related aldol reaction was also developed. Together, these reactions provide a new approach for the preparation of pharmaceutically relevant products possessing tetrasubstituted C-F centers.
摘要
本文报道了一种锌/苯丙醇催化的曼尼希反应，该反应使用氟化芳香酮作为亲核试剂，直接对映选择性和非对映选择性构建具有氟化四取代碳的β-氟胺基序。该反应可以在克级规模上进行，催化剂负载量低，且不影响其效率。此外，还开发了一种相关的羟醛反应。总之，这些反应为制备具有四取代C-F中心的药学相关产品提供了一种新方法。
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