化学
还原消去
对映选择合成
SN2反应
酰胺
配体(生物化学)
立体化学
组合化学
选择性
钯
催化作用
药物化学
有机化学
受体
生物化学
作者
Hojoon Park,Pritha Verma,Kai Hong,Jin‐Quan Yu
出处
期刊:Nature Chemistry
[Springer Nature]
日期:2018-06-11
卷期号:10 (7): 755-762
被引量:204
标识
DOI:10.1038/s41557-018-0048-1
摘要
The development of a Pd(ii)-catalysed enantioselective fluorination of C(sp3)−H bonds would offer a new approach to making chiral organofluorines. However, such a strategy is particularly challenging because of the difficulty in differentiating prochiral C(sp3)−H bonds through Pd(ii)-insertion, as well as the sluggish reductive elimination involving Pd−F bonds. Here, we report the development of a Pd(ii)-catalysed enantioselective C(sp3)−H fluorination using a chiral transient directing group strategy. In this work, a bulky, amino amide transient directing group was developed to control the stereochemistry of the C−H insertion step and selectively promote the C(sp3)−F reductive elimination pathway from the Pd(iv)–F intermediate. Stereochemical analysis revealed that while the desired C(sp3)−F formation proceeds via an inner-sphere pathway with retention of configuration, the undesired C(sp3)−O formation occurs through an SN2-type mechanism. Elucidation of the dual mechanism allows us to rationalize the profound ligand effect on controlling reductive elimination selectivity from high-valent Pd species. Metal-catalysed enantioselective fluorination of C(sp3)–H bonds is an attractive method for preparing chiral organofluorines, but the challenge of achieving both enantioselectivity and reductive elimination selectivity remains unsolved. Now, it has been demonstrated that a chiral amino amide transient directing group can serve as a ligand for a palladium catalyst that promotes both enantioselective C(sp3)–H insertion and C(sp3)–F-selective reductive elimination.
科研通智能强力驱动
Strongly Powered by AbleSci AI