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Abstract 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.
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Urea Ligand‐Promoted Chainwalking Heteroannulation for the Synthesis of 6‐ and 7‐membered Azaheterocycles
Abstract Typical approaches to heterocycle construction require significant changes in synthetic strategy even for a change as minor as increasing the ring size. The ability to access multiple heterocyclic scaffolds through a common synthetic approach, simply through trivial modification of one reaction component, would enable facile access to diverse libraries of structural analogues of core scaffolds. Here, we show that urea‐derived ligands effectively promote Pd‐mediated chainwalking processes to enable remote heteroannulation for the rapid construction of six‐ and seven‐membered azaheterocycles under essentially identical reaction conditions. This method demonstrates good functional group tolerance and effectively engages sterically hindered substrates. In addition, this reaction is applicable to target‐oriented synthesis, demonstrated through the formal synthesis of antimalarial alkaloid galipinine.
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- PAR ID:
- 10549139
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 30
- Issue:
- 66
- ISSN:
- 0947-6539
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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