Halder Pallabi, Iqubal Ashif, Mondal Krishanu, Mukhopadhyay Narottam, Das Parthasarathi
Department of Chemistry and Chemical Biology, Indian Institute of Technology (Indian School of Mines), Dhanbad 826004, India.
J Org Chem. 2023 Nov 3;88(21):15218-15236. doi: 10.1021/acs.joc.3c01725. Epub 2023 Oct 24.
A phosphine-free, efficient protocol for aminocarbonylation and carbonylative Suzuki-Miyaura coupling has been developed using a novel palladium complex, [Pd(DMAP)(OAc)]. The complex was successfully synthesized using a stoichiometric reaction between Pd(OAc) and DMAP in acetone at room temperature and characterized using single-crystal X-ray analysis. Only 5 mol % catalyst loading was sufficient for effective carbonylative transformations. "Chloroform-COware" chemistry was utilized for safe and facile insertion of the carbonyl unit using chloroform as an inexpensive CO source in a two-chamber setup. Various value-added pharmaceutically relevant compounds such as CX-516, CX-546, and farampator were synthesized using the technique. Furthermore, the commercially designed COware was engineered to COware-RB setup for sequential one-pot synthesis of indenoisoquinolines (topoisomerase I inhibitors).
使用新型钯配合物[Pd(DMAP)(OAc)]，开发了一种无膦、高效的氨甲酰化和羰基化铃木-宫浦偶联反应方案。该配合物通过在室温下丙酮中Pd(OAc)₂与DMAP的化学计量反应成功合成，并通过单晶X射线分析进行了表征。仅5 mol%的催化剂负载量就足以实现有效的羰基化转化。利用“氯仿-COware”化学方法，在两室装置中使用氯仿作为廉价的CO源，安全便捷地插入羰基单元。使用该技术合成了各种有附加值的药物相关化合物，如CX-516、CX-546和法安帕托。此外，将商业设计的COware改造为COware-RB装置，用于茚并异喹啉（拓扑异构酶I抑制剂）的连续一锅法合成。
