CH Bond Functionalization: Emerging Synthetic Tools for Natural Products and Pharmaceuticals

Abstract

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

Site-selective C–H arylation of primary aliphatic amines enabled by a catalytic transient directing group

“…Furthermore, the primary amines with a cyclic alkyl group reacted smoothly in this catalytic system (2j and 2k). Although many successful examples for functionalizing unactivated secondary sp 3 C−H bonds have been reported with the installation of a mono-or bidentate directing group on the substrates [5][6][7][8][9][10][11][12][13][14][15] , direct functionalization of these bonds remains a great challenge with carbonyl compounds using a transient directing group 37 and free aliphatic amines 23,30,31 , presumably due to the inherent steric hindrance. In this catalytic system, substrate 1l with cyclic methylene C−H bonds provided the γ-arylated product 2l in 23% yield, while arylation of noncyclic secondary C−H bonds was not realized.…”

Visible-Light Photocatalytic Double C–H Functionalization of Indoles: A Synergistic Experimental and Computational Study

“…[1][2][3][4] The prevalence of heterocycles in medicinal and biologically relevant molecules underscores the need for novel chemical methods to achieve complex and efficient transformations. [5][6][7][8][9][10][11] Latestage functionalization is becoming a leading strategy for efficient introduction of specific functional groups, 5 or to generate chemical libraries, for complex bioactive molecules. 5,7,10,12,13 Visible-light photocatalysis (VLPC) has recently emerged as a powerful manifold for late-stage C-H functionalization.…”

Palladium(0)-Catalyzed Benzylic C(<i>sp</i>³)–H Functionalization for the Concise Synthesis of Heterocycles and Its Applications

“…The application of C(sp 3 )-H functionalization to the total synthesis of complex natural products therefore remains a big challenge in synthetic chemistry, whereas C(sp 2 )-H functionalization is employed routinely. [30][31][32] We recently became interested in the development of Pd(0)-catalyzed C(sp 3 )-H functionalization reactions for the synthesis of complex molecules, and developed several new methods that addressed some of the problems described above. In this review, we provide a summary of our recent research on the Pd(0)-catalyzed benzylic C(sp 3 )-H functionalization reaction and its application.…”