手性化合物在自然界中无处不在, 其不对称合成一直是合成化学研究的热点. 近年来, 钯催化C(sp³)—H键不对称官能团化取得了非常重要的进展, 为手性分子的构筑提供了一种高效且简洁的方法. 通过手性配体的有效调控, 立体选择性地活化C(sp³)—H键, 形成手性环钯中间体, 继而被转化成各种官能团的方法受到了广大化学家的青睐. 总结了通过上述策略实现的C(sp³)—H键的不对称官能团化反应, 按照反应碳氢键的类别, 分为甲基碳氢键、张力环亚甲基碳氢键、杂原子α-位亚甲基碳氢键、苄位亚甲基碳氢键和非活化亚甲基碳氢键. 最后, 对该领域的局限性和未来发展进行了展望和总结.

Chiral molecules are ubiquitous in nature and play an important role in natural products, pharmaceuticals, agriculture, advanced materials, as well as living organisms. Therefore, the development of efficient strategies to enable the facile construction of enantiopure chiral compounds in an atom- and step-economical manner is of great importance. The enantioselective functionalization of C—H bonds without multi-steps transformation is arguably one of the most powerful and straightforward strategies to fulfill this goal. This emerging research field has been rapidly developed with the innovation of various chiral catalysts and/or ligands in recent years. In particular, significant advances have been achieved in palladium-catalyzed enantioselective functionalization of C(sp³)—H bonds, streamlining the efficient and concise construction of chiral molecules from readily available hydrocarbon feedstocks. The stereoselective functionalization of C(sp³)—H bonds with the assistance of chiral ligand to form a chiral palladacycle intermediate, which could be transformed into various chemical bonds to form functionalized chiral compounds, has attracted tremendous attention. Thus, this perspective summarizes the advances on palladium(II)-catalyzed enantioselective functionalization of C(sp³)—H bonds via asymmetric C—H palladation. According to the type of C—H bonds, this perspective is classified into several sections, including methyl C(sp³)—H bonds, methylene C(sp³)—H bonds in constrained cycloalkanes, functionalization of methylene C(sp³)—H bonds adjacent to α-heteroatom, benzylic methylene C(sp³)—H bonds, and unbiased methylene C(sp³)—H bonds. The emphasis of this perspective focuses on the discussion of the philosophy of developing novel chiral ligands and the mode of stereocontrol. The remaining limitations and challenges regarding to chemo- and enantioselective control in this field is also discussed. Further development of new chiral ligands and catalytic systems is expected to address these issues and expands the scope of this powerful synthetic strategy. We anticipate that this perspective might inspire more efforts to this emerging research field and the strategy might find wide applications in the synthesis of complicated chiral molecules, such as natural products and drugs.