Sharma Richa, Yadav Ravi Kant, Jain Mukesh, Joshi Jyoti, Chaudhary Sandeep
Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur 302017, India.
Laboratory of Bioactive Heterocycles and Catalysis, Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Raebareli (Transit Campus), Bijnor-Sisendi Road, Near CRPF Base Camp, Sarojini Nagar, Lucknow 226002, India.
J Org Chem. 2022 Mar 4;87(5):2668-2685. doi: 10.1021/acs.joc.1c02628. Epub 2022 Feb 4.
A highly efficient oxidant-switched palladium-catalyzed regioselective C-H/C-H cross-dehydrogenative coupling (CDC) for direct mono/bis-aroylation of substituted 1-phenyl-1-indazoles with various substituted aldehydes via C-H bond activation has been developed. In this study, Pd-catalyzed chelation-assisted mono- or bis-aroylation of substituted 1-phenyl1-indazoles depends on the type of oxidant being used for the CDC reaction. While mono--aroylation of substituted 1-phenyl-1-indazole was obtained using dicumylperoxide (DCP) as the oxidant, the bis--aroylation product has been afforded by the use of -butyl hydroperoxide (TBHP). Regardless of the greater activity at the C-3 position of 1-indazoles, the greater coordinating capacity of the N atom directed the aroylating group to the position, leaving behind the nondirected metalation pathway. The Pd-catalyzed operationally simplified methodology proceeded in the presence of oxidants with either DCP or TBHP in dichloroethane as the solvent at 110 °C for 16 h, which generated a miscellaneous variety of monosubstituted -benzoyl/acyl-1-aryl-1-indazoles / and bis-substituted -benzoyl-1-aryl-1-indazoles in ≤88% yields. The probable mechanistic pathway involves a free radical chelation-assisted approach that could be accomplished by the addition of an -generated oxidant-promoted benzoyl/acyl radical to the position of 1-phenyl-1-indazoles. A wide range of substrates, a high functional group tolerance, gram-scale synthesis, control/competitive experiments, and a variety of synthetic applications further exemplify the versatility of the developed methodology.
通过C-H键活化，开发了一种高效的氧化剂切换钯催化的区域选择性C-H/C-H交叉脱氢偶联（CDC）反应，用于各种取代醛与取代的1-苯基-1-吲唑直接进行单/双芳酰化反应。在本研究中，钯催化的取代1-苯基-1-吲唑的螯合辅助单芳酰化或双芳酰化反应取决于用于CDC反应的氧化剂类型。当使用过氧化二苯甲酰（DCP）作为氧化剂时，可得到取代的1-苯基-1-吲唑的单芳酰化产物，而使用叔丁基过氧化氢（TBHP）则可得到双芳酰化产物。尽管1-吲唑的C-3位活性更高，但N原子更强的配位能力将芳酰化基团导向了该位置，留下了非定向金属化途径。钯催化的操作简便的方法在110℃下于二氯乙烷中，在存在DCP或TBHP氧化剂的条件下进行16小时，生成了各种单取代的α-苯甲酰基/酰基-1-芳基-1-吲唑和双取代的α-苯甲酰基-1-芳基-1-吲唑，产率≤88%。可能的机理途径涉及自由基螯合辅助方法，该方法可通过将由氧化剂促进产生的苯甲酰基/酰基自由基加成到1-苯基-1-吲唑的α位置来实现。广泛的底物范围、高官能团耐受性、克级规模合成、对照/竞争实验以及各种合成应用进一步证明了所开发方法的通用性。
