Total synthesis is considered by many as the finest combination of art and science. During the last decades, several concepts were proposed for achieving the perfect vision of total synthesis, such as atom economy, step economy, or redox economy. In this context, C−H functionalization represents the most powerful platform that has emerged in the last years, empowering rapid synthesis of complex natural products and enabling diversification of bioactive scaffolds based on natural product architectures. In this review, we present an overview of the recent strategies towards the total synthesis of heterocyclic natural products enabled by C−H functionalization. Heterocycles represent the most common motifs in drug discovery and marketed drugs. The implementation of C−H functionalization of heterocycles enables novel tactics in the construction of core architectures, but also changes the logic design of retrosynthetic strategies and permits access to natural product scaffolds with novel and enhanced biological activities.
- Award ID(s):
- 1650766
- NSF-PAR ID:
- 10323801
- Date Published:
- Journal Name:
- Organics
- Volume:
- 2
- Issue:
- 4
- ISSN:
- 2673-401X
- Page Range / eLocation ID:
- 337 to 347
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Direct amination of C(sp3)−H bonds is of broad interest in the realm of C−H functionalization because of the prevalence of nitrogen heterocycles and amines in pharmaceuticals and natural products. Reported here is a combined electrochemical/photochemical method for dehydrogenative C(sp3)−H/N−H coupling that exhibits good reactivity with both sp2and sp3N−H bonds. The results show how use of iodide as an electrochemical mediator, in combination with light‐induced cleavage of intermediate N−I bonds, enables the electrochemical process to proceed at low electrode potentials. This approach significantly improves the functional‐group compatibility of electrochemical C−H amination, for example, tolerating electron‐rich aromatic groups that undergo deleterious side reactions in the presence of high electrode potentials.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/org2040018
