Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents
Iron-Catalyzed Enantioselective Cross-Coupling Reactions of α-Chloroesters with Aryl Grignard Reagents
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DOI：
10.1021/jacs.5b02277
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发表时间：
2015-06-10
影响因子：
15
通讯作者：
Nakamura, Masaharu
中科院分区：
文献类型：
--
作者：
Jin, Masayoshi;Adak, Laksmikanta;Nakamura, Masaharu
报道了第一个铁催化的有机金属化合物与有机亲电试剂之间的对映选择性交叉偶联反应。在催化量的铁盐和手性双膦配体存在下，合成通用的外消旋α-氯代和α-溴代烷酸酯与芳基格氏试剂偶联，以高产率得到可接受的和合成有用的对映选择性的产物（91：9）：生成的α-芳基链烷酸酯容易转化为具有高光学富集的相应α-芳基链烷酸（er高达>99：1）。自由基探针实验的结果是一致的甲烷化，涉及形成的烷基自由基中间体，其经历随后的对映收敛芳基化在分子间的方式。开发的非对称耦合不仅提供了简便。和实际获得各种手性α-芳基链烷酸衍生物，其具有重要的药学重要性，而且也是在铁催化的有机金属转化中控制对映选择性的基础。
The first iron-catalyzed enantioselective cross-coupling reaction between an organometallic compound and an organic electrophile is reported. Synthetically versatile racemic alpha-chloro- and alpha-bromoalkanoates were coupled with aryl Grignard reagents in the presence of catalytic amounts of an iron salt and a chiral bisphosphine ligand, giving the products in high yields with acceptable and synthetically Useful enantioselectivities (er up to 91:9): The produced alpha-arylalkanoates were readily converted to the corresponding alpha-arylalkanoic acids with high optical enrichment (er up to >99:1) via simple deprotections/recrystallizations. The results of radical probe experiments are consistent with a methanism that involves the formation of an alkyl radical intermediate, which undergoes subsequent enantioconvergent arylation in an intermolecular manner. The developed asymmetric coupling offers not only facile. and practical access to various chiral alpha-arylalkanoic acid derivatives, which are of significant pharmaceutical importance, but also a basis Of controlling enantioselectivity in an iron-catalyzed organometallic transformation.