Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling

We
report the development of a new class of guanidine-containing
peptides as multifunctional ligands for transition-metal catalysis
and its application in the remote desymmetrization of diarylmethanes
via copper-catalyzed Ullman cross-coupling. Through design of these
peptides, high levels of enantioinduction and good isolated yields
were achieved in the long-range asymmetric cross-coupling (up to 93:7
er and 76% yield) between aryl bromides and malonates. Our mechanistic
studies suggest that distal stereocontrol is achieved through a Cs-bridged
interaction between the Lewis-basic C-terminal carboxylate
of the peptides with the distal arene of the substrate.

本研究报道了一类新型含胍基肽的开发工作，该类肽可作为过渡金属催化的多功能配体，并将其应用于铜催化乌尔曼交叉偶联（Ullman cross-coupling）反应实现二芳基甲烷的远程去对称化。通过对这类肽的合理设计，我们在芳基溴化物与丙二酸酯的远程不对称交叉偶联反应中，实现了高水平的对映诱导效果与良好的分离产率：对映体比率（er）最高可达93:7，分离产率达76%。我们的机理研究表明，该反应的远端立体调控是通过肽的路易斯碱性C端羧酸盐与底物远端芳烃之间形成的铯桥联相互作用实现的。