Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA.
Pfizer Oncology Medicinal Chemistry, 10770 Science Center Drive, San Diego, CA 92121, USA.
Angew Chem Int Ed Engl. 2022 Mar 21;61(13):e202114346. doi: 10.1002/anie.202114346. Epub 2022 Feb 2.
In this study, we systematically evaluate different ambiphilic organohalides for their ability to participate in anti-selective carbo- or heteroannulation with non-conjugated alkenyl amides under Pd /Pd catalysis. Detailed optimization of the reaction conditions has led to protocols for synthesizing tetrahydropyridines, tetralins, pyrrolidines, and other carbo/heterocyclic cores via [n+2] (n=3-5) (hetero)annulation. Expansion of scope to otherwise unreactive ambiphilic haloketones through Pd /amine co-catalysis is also demonstrated. Compared to other annulation processes, this method proceeds via a distinct Pd /Pd mechanism involving Wacker-type directed nucleopalladation. This difference results in unique reactivity and selectivity patterns, as revealed through assessment of reaction scope and competition experiments.
在这项研究中，我们系统地评估了不同的两性有机卤化物在 Pd/Pd 催化下与非共轭烯基酰胺进行反选择性碳环或杂环化反应的能力。通过对反应条件的详细优化，我们制定了通过[n+2]（n=3-5）（杂）环化合成四氢吡啶、四氢萘、吡咯烷和其他碳/杂环核的方案。通过 Pd/胺共催化作用，将范围扩展到其他无反应性的两性卤代酮也得到了证明。与其他环化过程相比，这种方法通过一种独特的 Pd/Pd 机制进行，涉及到 Wacker 型导向的亲核钯化。通过评估反应范围和竞争实验，这种差异导致了独特的反应性和选择性模式。
