基于脯氨酸的新型手性叔胺N-氧化物合成

Synthesis of Proline-based Novel Chiral Tertiary Amine-derived N-Oxides

叔胺衍生的N-氧化物配体的结构多样性合成仍然是不对称催化领域最重要的课题之一。以光学纯的脯氨酰胺或羟脯氨酰胺1与各种取代的吡啶-2-甲醛2发生缩合环化反应,生成中间体3,然后中间体3中的氮原子在氧化剂m-CPBA(间氯过氧苯甲酸)的作用下发生氧化反应,合成了24个新型手性叔胺氮氧化合物4aa~4bk,总产率43%~58%,dr值为10/1~>20/1,其结构经^(1)H NMR,^(13)C NMR和HR-MS(ESI-TOF)表征,化合物4ai的绝对构型(3S,4R,7aS)通过单晶X-射线衍射进行了进一步确定。该类化合物以L-脯氨酸衍生物作为手性源制备了手性N-氧化物,今后可以为金属不对称催化提供新配体筛选。

The structural diversity synthesis of tertiary amines-derived N-oxide ligands remains one of the most important topics in the field of asymmetric catalysis.In this paper,using optically pure prolamides or hydroxyprolamides 1 as the chiral source,the intermediates 3 were synthesized by condensation cyclization with various substituted pyridine-2-formaldehydes 2,and then the nitrogen atom in the intermediates 3 was oxidized under the action of chloro perbenzoic acid,an oxidant,to provide 24 chiral proline-based tertiary amine-derived N-oxides 4aa~4bk in 43%~58%overall yield and dr 10/1~>20/1.The structures of products 4 were characterized by^(1)H NMR,^(13)C NMR and HR-MS(ESI-TOF).The absolute configuration(3S,4R,7aS)of compound 4ai was further determined by the single crystal X-ray diffraction.These compounds,based on L-proline derivatives serving as chiral sources,can provide new ligand screening for Lewis acid asymmetric catalysis in the future.