One-Pot Preparation of Enantiopure Fluorinated β-Amino Acid Precursors: Enantiopure Fluorinated β-Amino Acid Precursors
One-Pot Preparation of Enantiopure Fluorinated β-Amino Acid Precursors: Enantiopure Fluorinated β-Amino Acid Precursors
复制标题
对映体纯氟化 β-氨基酸前体的一锅制备： 对映体纯氟化 β-氨基酸前体
DOI：
10.1002/ejoc.201402369
复制
发表时间：
2014
影响因子：
2.8
通讯作者：
Brenner-Moyer, Stacey E.
中科院分区：
文献类型：
--
作者：
Jones, Joshua H.;Appayee, Chandrakumar;Brenner-Moyer, Stacey E.
手性β-氟胺和β，β-二氟胺是药物化合物中常见的亚结构。工业合成通常使用对映体起始材料、手性助剂或拆分对映体或非对映异构体混合物，以对映体形式安装这些官能团。为了更好地获得这些亚结构，我们最近开发了第一个催化的对映选择性烯烃氨基卤化反应，它可以在一个烧瓶中从非手性烯醛原料中制备手性β-氟胺。本文介绍了将该方法推广到β-氨基-α，α-二氟羰基化合物的制备。具体地说，碳-氮和碳-氟键的形成反应在有机级联反应中结合起来，生成了β-氨基-α，α-二氟羰基化合物，在β-位上含有烷基取代基。因此，这种方法在机械上不同于现有的一锅催化对映体选择性制备氟化β-氨基酸前体的方法，并与之互补。
Chiral β‐fluoro amines and β,β‐difluoro amines are common substructures in medicinal compounds. Industrial syntheses typically use enantiopure starting materials, chiral auxiliaries, or the resolution of enantiomeric or diastereomeric mixtures to install these functionalities in enantiopure form. With the goal of improving access to these substructures, we recently developed the first catalytic enantioselective olefin aminohalogenation reaction, which produced chiral β‐fluoro amines in a single flask from achiral enal starting materials. This paper describes the extension of this method to the preparation of β‐amino‐α,α‐difluoro carbonyl compounds. Specifically, carbon–nitrogen and carbon–fluorine bond‐forming reactions were combined in an organocascade reaction to produce β‐amino‐α,α‐difluoro carbonyl compounds containing alkyl substituents at the β‐position. As such, this method is mechanistically distinct from, and complementary to, existing one‐pot catalytic enantioselective methods for the preparation of fluorinated β‐amino acid precursors.