Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp3)–H Bonds

The
transition-metal-catalyzed direct C–H bond fluorination
is an attractive synthetic tool toward the preparation of organofluorines.
While many methods exist for the direct sp3 C–H
functionalization, site-selective fluorination of unactivated sp3 carbons remains a challenge. Direct, highly site-selective
and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed
bidentate ligand-directed C–H bond functionalization process
on unactivated sp3 carbons is reported. With this approach,
a wide variety of β-fluorinated amino acid derivatives and aliphatic
amides, important motifs in medicinal and agricultural chemistry,
were prepared with palladium acetate as the catalyst and Selectfluor
as the fluorine source.

过渡金属催化的直接C-H键氟化反应是制备有机氟化合物的一种极具吸引力的合成工具。尽管存在多种直接对sp3碳进行官能化的方法，但对于非活化sp3碳的位点选择氟化仍然是一项挑战。本文报道了一种通过在非活化sp3碳上利用钯催化的双齿配体导向的C-H键官能化过程，实现直链脂肪族酰胺的位点选择性和对映选择性氟化。借助该方法，以乙酸钯为催化剂，Selectfluor为氟源，成功合成了多种β-氟化氨基酸衍生物和脂肪族酰胺，这些化合物在医药和农业化学中具有重要意义。