Catalytic enantioselective synthesis of atropisomeric biaryls by a cation-directed O-alkylation
Catalytic enantioselective synthesis of atropisomeric biaryls by a cation-directed O-alkylation
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DOI：
10.1038/nchem.2710
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发表时间：
2017-06-01
期刊：
影响因子：
21.8
通讯作者：
Smith, Martin D.
中科院分区：
文献类型：
--
作者：
Jolliffe, John D.;Armstrong, Roly J.;Smith, Martin D.
以1,1′-双-2-萘酚（BINOL）为代表的轴向手性双芳基化合物是催化剂、天然产物和药物的关键成分。这些材料通常是通过金属介导的交叉偶联、芳环的从头构建、点向轴手性转移或现有联芳基的缩选择性转化以富集对映体形式合成的。在这里，我们报道了一种高度对映选择性的有机催化方法，通过阳离子导向的o -烷基化合成了atroisomer biaryl。手性奎尼丁衍生的铵盐在烷基化剂的存在下，在碱性条件下处理外消旋1-芳基-2-四酮，可导致选择性o -烷基化，e.r高达98:2。用DDQ氧化可以得到c -2对称和非对称的BINOL衍生物，而不会影响e.r。我们提出手性铵反离子可以区分快速平衡的atrosom异构烯醇化物，从而导致高度的atroselective o -烷基化。这种动态动力学分解过程为合成对映体富集的atrosom异构材料提供了一种通用的方法。
Axially chiral biaryls, as exemplified by 1,1'-bi-2-naphthol (BINOL), are key components of catalysts, natural products and medicines. These materials are synthesized conventionally in enantioenriched form through metal-mediated cross coupling, de novo construction of an aromatic ring, point-to-axial chirality transfer or an atropselective transformation of an existing biaryl. Here, we report a highly enantioselective organocatalytic method for the synthesis of atropisomeric biaryls by a cation-directed O-alkylation. Treatment of racemic 1-aryl-2-tetralones with a chiral quinidine-derived ammonium salt under basic conditions in the presence of an alkylating agent leads to atropselective O-alkylation with e.r. up to 98:2. Oxidation with DDQ gives access to C-2-symmetric and non-symmetric BINOL derivatives without compromising e.r. We propose that the chiral ammonium counterion differentiates between rapidly equilibrating atropisomeric enolates, leading to highly atropselective O-alkylation. This dynamic kinetic resolution process offers a general approach to the synthesis of enantioenriched atropisomeric materials.