Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, United States.
J Am Chem Soc. 2020 Jun 10;142(23):10516-10525. doi: 10.1021/jacs.0c03589. Epub 2020 May 29.
The formation of alkyl-palladium complexes via the nucleopalladation of alkenes is the entry point for a wide range of diverse reactions. One possibility is that the intermediate alkyl-Pd complexes can undergo a "chain-walking" event, to allow for remote functionalization through various termination processes. However, there are few methods to selectively interrupt the chain-walking process at a prescribed location. Herein, we demonstrate that a variety of homoallylic protected amines undergo an interrupted enantioselective relay Heck reaction to give enantioenriched allylic amine products. The selectivity of this process can be diverted to exclusively yield the ene-amide products by virtue of changing the nature of the amine protecting group. To rationalize this observation, we combine experiment and computation to investigate the mechanism of the chain-walking process and termination events. Isotopic labeling experiments and the computed reaction pathways suggest that the system is likely under thermodynamic control, with the selectivity being driven by the relative stability of intermediates encountered during chain-walking. These results illustrate that the chain-walking of alkyl-palladium complexes can be controlled through the alteration of thermodynamic processes and provides a roadmap for exploiting these processes in future reaction development.
通过烯烃的亲核钯化形成烷基钯配合物是广泛的各种反应的切入点。一种可能性是，中间的烷基-Pd 配合物可以经历“链行走”事件，以允许通过各种终止过程进行远程官能化。然而，很少有方法可以在规定的位置选择性地中断链行走过程。在此，我们证明各种偕胺保护的胺经历了中断的对映选择性接力 Heck 反应，以得到对映富集的烯丙基胺产物。通过改变胺保护基的性质，可以将该过程的选择性转向仅生成烯酰胺产物。为了合理化这一观察结果，我们结合实验和计算来研究链行走过程和终止事件的机理。同位素标记实验和计算的反应途径表明，该体系可能处于热力学控制之下，选择性由链行走过程中遇到的中间体的相对稳定性驱动。这些结果表明，烷基钯配合物的链行走可以通过改变热力学过程来控制，并为在未来的反应开发中利用这些过程提供了路线图。
