美国斯克利普斯研究所余金权团队报道了阳离子钯配合物对酮和酯的β-C-H键功能化。相关研究成果发表在2025年1月8日出版的国际学术期刊《自然》。

C-H活化是有机分子功能化的最直接方式。该领域的许多进展仍然需要特定的引导，来实现必要的活动和选择性。开发由天然官能团引导的C-H活化反应，对于它们在合成中的广泛应用至关重要。在过去的十年里，开发了几代双功能配体，使游离羧酸、游离脂肪胺、天然酰胺和醇的C（sp³）-H活化反应成为可能。然而，酮和羧酸酯的有效催化剂仍有待实现。

该文中，研究人员报告了不同的甲基β-CH官能化，包括分子间芳基化、羟基化和酮和羧酸酯，与单保护氨基中性酰胺（MPANA）配体的分子内C（sp³）-H/C（sp²）-H偶联。通过MPANA配体和HBF₄的组合原位产生阳离子Pd（II）配合物，对于实现反应性至关重要。

这些反应与环酮和内酰胺的相容性，提供了一种获得螺环和稠环系统的方法。机理实验和密度泛函理论研究，表明了阳离子Pd配合物与MPANA配体，在增强催化剂-底物亲和力和促进CH裂解步骤中的作用。

附：英文原文

Title: β-C-H bond functionalization of ketones and esters by cationic Pd complexes

Author: Li, Yi-Hao, Chekshin, Nikita, Lu, Yilin, Yu, Jin-Quan

Issue&Volume: 2025-01-08

Abstract: C–H activation is the most direct way of functionalizing organic molecules. Many advances in this field still require specific directing groups to achieve the necessary activity and selectivity. Developing C–H activation reactions directed by native functional groups is essential for their broad application in synthesis1. Over the past decade, several generations of bifunctional ligands developed have enabled C(sp3)–H activation reactions of free carboxylic acids2, free aliphatic amines3, native amides4,5 and alcohols6. However, an effective catalyst for ketones and carboxylic esters remains to be realized. Here we report diverse methyl β-CH functionalizations, including intermolecular arylation, hydroxylation and intramolecular C(sp3)–H/C(sp2)–H coupling of ketones and carboxylic esters with a monoprotected amino neutral amide (MPANA) ligand. The in situ generation of cationic Pd(II) complexes by the combination MPANA ligand and HBF4 is crucial for achieving the reactivity. The compatibility of these reactions with cyclic ketones and lactams provides a method to access spirocyclic and fused ring systems. Mechanistic experiments and density functional theory studies support the role of cationic Pd complexes with MPANA ligands in enhancing catalyst–substrate affinity and facilitating the CH cleavage step.

DOI: 10.1038/s41586-024-08281-4

Source: https://www.nature.com/articles/s41586-024-08281-4