Allylic C-H oxygenation of unactivated internal olefins by the Cu/azodiformate catalyst system.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39833256.
- Also identified by DOI 10.1038/s41467-025-56230-0 and PMC identifier 11756401.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Allylic ethers and alcohols are essential structural motifs commonly present in natural products and pharmaceuticals. Direct allylic C-H oxygenation of internal alkenes is one of the most direct methods, bypassing the necessity for an allylic leaving group that is needed in the traditional Tsuji-Trost reaction. Herein, we develop an efficient and practical method for synthesizing (E)-allyl ethers from readily available internal alkenes and alcohols or phenols via selective allylic C-H oxidation. Key advances include the use of a Cu/Azodiformate catalyst system to facilitate remote allylic C-H activation and the achievement of excellent chemoselectivity through a dynamic ligand exchange strategy using a bis(sulfonamide) ligand. This method features a broad substrate scope and functional group tolerance, successfully applied to the synthesis of various challenging medium-sized cyclic ethers (7-10 members) and large-ring lactones (14-20 members), with high regioselectivity and stereoselectivity.