Luo Zheng, Zhang Xiaoyu, Li Zaiyang, Luo Meiming, Zeng Xiaoming
Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University Chengdu 610064 China
Chem Sci. 2024 Jun 12;15(29):11428-11434. doi: 10.1039/d4sc02967d. eCollection 2024 Jul 24.
The mild catalytic generation of ketyl radicals for organic transformations remains an unsolved issue, although it facilitates the discovery of metal-catalyzed reactions with the features of high functional group tolerance. Here, we report the generation of the ketyl radicals and coupling with alkynes that was enabled by cost-effective chromium catalysis, allowing for the formation of valuable -exocyclic allyl alcohols with high stereo- and chemoselectivity. A broad range of synthetically useful functional groups that are sensitive to strong reductants are compatible with the catalytic system, providing access to diverse substituted -exocyclic allyl alcohols under mild conditions. Appended hydroxyl groups in products are facilely late-stage functionalized in accessing numerous derivatives, as well as the enantio-enrichment of exocyclic allyl alcohol using chiral ligands. Mechanistic studies suggest that bipyridine-ligated Cr(ii) complex serves as a reactive catalyst enabling the generation of the ketyl radical for coupling, giving vinyl radical, followed by the combination of Cr and transmetalation with CpZrCl moiety in affording oxazirconiumacycle. This reaction provides a new opportunity for the mild formation of transient ketyl radicals from widely accessible aliphatic aldehydes for coupling with Earth-abundant metal catalysis.
尽管温和催化生成酮基自由基有助于发现具有高官能团耐受性的金属催化反应，但用于有机转化的这一过程仍是一个未解决的问题。在此，我们报道了通过经济高效的铬催化实现酮基自由基的生成及其与炔烃的偶联反应，从而能够以高立体选择性和化学选择性形成有价值的环外烯丙醇。一系列对强还原剂敏感的合成上有用的官能团与该催化体系兼容，使得在温和条件下能够获得多种取代的环外烯丙醇。产物中附加的羟基在后期易于官能化以获得众多衍生物，同时也能使用手性配体对外环烯丙醇进行对映体富集。机理研究表明，联吡啶配位的Cr(ii)配合物作为活性催化剂，能够生成用于偶联的酮基自由基，进而产生乙烯基自由基，随后Cr与CpZrCl部分进行金属转移反应生成恶唑锆环。该反应为从广泛可得的脂肪醛温和生成瞬态酮基自由基以与储量丰富的金属催化进行偶联提供了新机会。
