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

以前，我们实现了铜催化的不对称共轭加成（ACA）反应，通过使用的CH 2-桥接的羟基-酰胺-官能化的唑盐。我们设计并合成了一种（CH 2）2-桥连的羟基酰胺基功能化的唑盐。与Cu（OTf）_2与CH_2-桥连的偶氮唑盐的ACA反应相比，Cu（OTf）_2与（CH_2）_2-桥连的偶氮唑盐的ACA反应生成了构型相反的1，4-加合物。此外，通过将Cu预催化剂从Cu（OTf）2改变为Cu（acac）2，观察到在ACA反应中具有相同配体前体的双重对映选择性控制。此外，还开发了一种新的酯-酰胺官能化的唑盐。发现在使用酯-酰胺-官能化的唑鎓盐的ACA反应中缀合加合物的绝对构型不同于在使用羟基-酰胺-官能化的唑鎓盐的ACA反应中获得的缀合加合物的绝对构型。

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.