Asymmetric Reductive Mannich Reaction to Ketimines Catalyzed by a Cu(I) Complex
Asymmetric Reductive Mannich Reaction to Ketimines Catalyzed by a Cu(I) Complex
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DOI：
10.1021/ja8069727
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发表时间：
2008-12-03
影响因子：
15
通讯作者：
Shibasaki, Masakatsu
中科院分区：
文献类型：
--
作者：
Du, Yao;Xu, Li-Wen;Shibasaki, Masakatsu
以CuOAc-PPh_3或ClOAc-MePPh_2为催化剂（5mol%），频哪醇硼烷为还原剂，研究了酮亚胺与α，β-不饱和酯的高非对映选择性还原Mannich偶联反应。将该平台方法扩展到使用CuOAc-DIFLUORPHOS作为催化剂（10摩尔%）的酮亚胺的第一催化不对称还原Mannich反应。将还原剂从频哪醇硼烷转换为（EtO）（3）SiH是诱导高对映选择性（82- 93%ee）的关键。还保持了高的非对映选择性（3：1类似于30：1）。因此，含有连续的四-和三取代的碳的产物被催化合成具有高立体选择性。通过在酸性条件下的简单处理，产物转化为α，β，β-三取代（β（2，3，3））氨基酸衍生物，而没有任何外消旋和差向异构化。该方法是β（2，3，3）-氨基酸衍生物的催化不对称合成的第一个入口，β（2，3，3）-氨基酸衍生物构成重要的生物重要分子的手性构件。
A highly diastereoselective reductive Mannich coupling of ketimines and alpha,beta-unsatLirated esters was developed using CuOAc-PPh3 or CLOAc-MePPh2 complex as a catalyst (5 mol %) and pinacolborane as a reducing reagent, The reaction was easily conducted at room temperature, and the substrate generality was broad. This platform methodology was extended to the first catalytic asymmetric reductive Mannich reaction of ketimines using CuOAc-DIFLUORPHOS as the catalyst (10 mol %). Switching the reducing reagent from pinacolborane to (EtO)(3)SiH was key to inducing the high enantioselectivity (82-93% ee). High diastereoselectivity was also maintained (3:1 similar to 30:1). Thus, products containing contiguous tetra- and trisubstituted carbons were catalytically synthesized with high stereoselectivities. Products were converted to alpha,beta,beta-trisubstituted (beta(2,3,3)) amino acid derivatives without any racemization and epimerization through simple treatment under acidic conditions. This method is the first entry of the catalytic asymmetric synthesis of beta(2,3,3)-amino acid derivatives, which constitute important chiral building blocks of biologically significant molecules.