Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
J Am Chem Soc. 2022 Mar 23;144(11):4727-4733. doi: 10.1021/jacs.1c13586. Epub 2022 Mar 14.
Pd(II)-catalyzed site-selective β- and γ-C(sp)-H arylation of primary aldehydes is developed by rational design of L,X-type transient directing groups (TDG). External 2-pyridone ligands are identified to be crucial for the observed reactivity. By minimizing the loading of acid additives, the ligand effect is enhanced to achieve high reactivities of the challenging primary aldehyde substrates. Site selectivity can be switched from the proximate to the relatively remote position by changing the bite angle of TDG to match the desired palladacycle size. Experimental and computational investigations support this rationale for designing TDG to potentially achieve remote site-selective C(sp)-H functionalizations.
钯（II）催化的伯醛基β-和γ-C（sp）-H 芳基化反应是通过合理设计 L，X 型瞬态导向基团（TDG）来实现的。外部 2-吡啶酮配体被确定为观察到的反应性的关键。通过最小化酸添加剂的负载量，增强了配体效应，从而实现了具有挑战性的伯醛底物的高反应活性。通过改变 TDG 的咬合角度以匹配所需的钯环大小，可以将位点选择性从邻近位置切换到相对较远的位置。实验和计算研究支持了这种设计 TDG 的原理，以潜在地实现远程位点选择性 C（sp）-H 官能化。
