Palladium-Catalyzed C(sp3)–H Bond Functionalization of Aliphatic Amines
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
© 2018 Elsevier Inc. Methods that enable the practical and selective functionalization of traditionally unreactive aliphatic C–H bonds have synthetic applications in fields ranging from drug discovery to advanced materials. One of the major challenges is the development of strategically important reactions on aliphatic molecules containing synthetically useful functional groups. Aliphatic amines are central to the function of many biologically active molecules, as evidenced by their prevalence in a large number of pharmaceutical agents. Over the past decade, chemists have found ways to tailor the electronic and steric properties of directing functionalities and ligands to enable palladium-catalyzed C–H activation of aliphatic amine derivatives. Many of these methods have been successfully applied to the synthesis of pharmaceuticals and complex natural products. This review provides an overview of these methods and describes recent contributions, as well as the remaining challenges, in this emerging field. The preparation and functionalization of complex aliphatic amines remains an important challenge to synthetic and medicinal chemists given that their structural and functional properties are fundamental to biological activity. With the development of C–H functionalization, Pd-catalyzed methods for aliphatic amines have emerged as a powerful approach for the synthesis of variants of these molecules. Central to many of the designs is the facilitating role of tailored amine groups, which steer the C–H bond activation during cyclometallation. This review discusses three major strategies of using directing functionalities that enable the selective C–H functionalization of aliphatic amines, including the amine-derived directing-group strategy, the transient-directing-group strategy, and the native-amine-directed strategy. We believe that these methods will inspire new applications of aliphatic amine C–H functionalization in the synthesis of nitrogen-containing pharmaceuticals and natural products. Aliphatic amines are central to the function of many biologically active molecules. Over the past decade, Pd-catalyzed C–H functionalization has gradually maturated into a powerful tool for the synthesis and functionalization of these nitrogen-containing molecules. Three major strategies of using directing functionalities that enable the selective C–H functionalization of aliphatic amines—including the amine-derived directing-group strategy, the transient-directing-group strategy, and the native-amine-directed strategy—are discussed in this review.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
2451-9294