Wang Le, She Yuan, Xiao Jie, Li Zi-Hao, Zhang Shen-Yuan, Lian Peng-Fei, Ding Tong-Mei, Zhang Shu-Yu
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, PR China.
Nat Commun. 2025 Jan 20;16(1):870. doi: 10.1038/s41467-025-56230-0.
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.
烯丙基醚和醇是天然产物和药物中常见的重要结构基序。内烯烃的直接烯丙基C-H氧化是最直接的方法之一，绕过了传统Tsuji-Trost反应中所需的烯丙基离去基团。在此，我们开发了一种高效实用的方法，通过选择性烯丙基C-H氧化，从容易获得的内烯烃和醇或酚合成(E)-烯丙基醚。关键进展包括使用铜/偶氮二甲酸酯催化剂体系促进远程烯丙基C-H活化，以及通过使用双(磺酰胺)配体的动态配体交换策略实现优异的化学选择性。该方法具有广泛的底物范围和官能团耐受性，成功应用于各种具有挑战性的中等大小环醚(7-10元)和大环内酯(14-20元)的合成，具有高区域选择性和立体选择性。
