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 S_N2-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.

Pd（ii）催化的C（sp ³）-H键对映选择性氟化的发展将提供一种制备手性有机氟的新方法。然而，由于难以通过Pd（ii）插入区分前手性C（sp ³）-H键，以及涉及Pd-F键的缓慢的还原消除，这种策略特别具有挑战性。在这里，我们报告开发的Pd（ii）催化对映选择性C（sp ³）-H氟化，使用手性瞬态导向基团策略。在这项工作中，开发了一个庞大的氨基酰胺瞬态导向基团，以控制CH插入步骤的立体化学，并选择性地促进Pd（iv）-F中间体的C（sp ³）-F还原消除途径。立体化学分析显示，尽管所需的C（sp ³）-F形成通过保留构型的内球途径进行，但不希望的C（sp ³）-O形成则通过S _N 2型机制发生。对双重机理的阐明使我们能够合理地控制从高价Pd物种还原还原消除选择性的深刻配体效应。