Development of second generation of anionic tethered NHC ligand for achievement of reversal of enantioselectivity in catalytic asymmetric reaction

以前，我们通过使用CH2桥联的羟胺功能化的氮杂环盐实现了铜催化的不对称共轭加成(ACA)反应。现在，我们设计并合成了一种(CH2)2-桥联羟基酰胺功能化的氮盐。与铜(OTf)2与CH2桥联天青盐在ACA反应中生成的产物相比，(CH2)2桥联配体与Cu(OTf)2结合生成了构型相反的1，4-加合物。此外，通过将铜预催化剂由铜(OTf)2改为铜(Acac)2，观察到了同一配体前体在ACA反应中的双重对映选择性控制。此外，还开发了一种新的酯酰胺功能化的偶氮盐。结果表明，用酯酰胺功能化的天青盐进行ACA反应得到的共轭加合物的绝对构型与用羟胺官能化的天青盐进行的ACA反应的绝对构型不同。

Previously, we achieved the Cu-catalyzed asymmetric conjugate addition (ACA) reaction by the use of a CH2-bridged hydroxy-amide-functionalized azolium salt. Now, we designed and synthesized a (CH2)2-bridged hydroxy-amide-functionalized azolium salt. In comparison with the product which was obtained in the ACA reaction by Cu(OTf)2 combined with CH2-bridged azolium salt, the combination of Cu(OTf)2 with (CH2)2-bridged ligand led to the formation of the 1,4-adduct with opposite configuration. In addition, dual enantioselective control in the ACA reaction with the same ligand precursor was observed by changing the Cu precatalyst from Cu(OTf)2 to Cu(acac)2. Furthermore, a new ester-amide-functionalized azolium salt was also developed. It was found that the absolute configuration of the conjugate adduct in the ACA reaction using the ester-amide-functionalized azolium salt differs from that obtained in the ACA reaction using the hydroxy-amide-functionalized azolium salt.