Department of Chemistry, Birla Institute of Technology and Science, Pilani, Pilani Campus, Rajasthan 333031, India.
Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Telangana 500078, India.
J Org Chem. 2023 Feb 17;88(4):2344-2357. doi: 10.1021/acs.joc.2c02756. Epub 2023 Feb 3.
A Selectfluor-promoted oxidative coupling of quinoxalin-2(1)-ones with alcohols, amines, thiols, and selenols leading to the formation of C-O, C-N, C-S, and C-Se bonds has been developed. The protocol provided good to excellent (53-95%) yields of a wide range of quinoxalin-2(1)-ones decorated with alkoxy, alkylamino, alkylthio, and arylselenyl groups at the C3-position under metal- and photocatalyst-free conditions. The reaction is believed to proceed through a radical pathway. A broad substrate scope including bioactive molecules, mild reaction conditions, readily available coupling partners, high yields, scalability, step-economy, and metal- and photocatalyst-free conditions are the highlighting features of the method. The synthetic utility of the developed protocol was demonstrated by gram-scale synthesis, C3-alkoxylation of quinoxaline-2(1)-one with natural alcohols, and synthesis of aldose reductase (ALR2) inhibitor and histamine-4 receptor antagonist in good yields.
一种通过 Selectfluor 促进的喹喔啉-2(1H)-酮与醇、胺、硫醇和硒醇的氧化偶联反应已经被开发出来，该反应可以在无金属和光催化剂的条件下生成 C-O、C-N、C-S 和 C-Se 键。该方法具有广泛的底物范围，包括生物活性分子，反应条件温和，使用的偶联试剂易得，产率高，可规模化，经济性好，且无需使用金属和光催化剂等优点。该方法的突出特点还包括：通过自由基途径进行反应；通过克级规模合成、天然醇对喹喔啉-2(1H)-酮的 C3-烷氧基化以及以良好产率合成醛糖还原酶（ALR2）抑制剂和组氨酸-4 受体拮抗剂，展示了其合成实用性。所开发的方法提供了具有广泛的烷氧基、烷基氨基、烷基硫基和芳硒基取代的喹喔啉-2(1H)-酮，产率为 53-95%。
