Expedient synthesis of E-hydrazone esters and 1H-indazole scaffolds through heterogeneous single-atom platinum catalysis

• Main Authors: Liu, Cuibo, Chen, Zhongxin, Yan, Huan, Xi, Shibo, Yam, Kah Meng, Gao, Jiajian, Du, Yonghua, Li, Jing, Zhao, Xiaoxu, Xie, Keyu, Xu, Haisen, Li, Xing, Leng, Kai, Pennycook, Stephen J., Liu, Bin, Zhang, Chun, Koh, Ming Joo, Loh, Kian Ping
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2020
• Subjects: Engineering::Chemical engineering; E-hydrazone Esters; 1H-indazole
• Online Access: https://hdl.handle.net/10356/144004
• Institution: Nanyang Technological University

Unprotected E-hydrazone esters are prized building blocks for the preparation of 1H-indazoles and countless other N-containing biologically active molecules. Despite previous advances, efficient and stereoselective synthesis of these compounds remains nontrivial. Here, we show that Pt single atoms anchored on defect-rich CeO2 nanorods (Pt1/CeO2), in conjunction with the alcoholysis of ammonia borane, promotes exceptionally E-selective hydrogenation of α-diazoesters to afford a wide assortment of N-H hydrazone esters with an overall turnover frequency of up to 566 hours-1 upon reaction completion. The α-diazoester substrates could be generated in situ from readily available carboxylic esters in one-pot hydrogenation reaction. Utility is demonstrated through concise, scalable synthesis of 1H-indazole-derived pharmaceuticals and their 15N-labeled analogs. The present protocol highlights a key mechanistic nuance wherein simultaneous coordination of a Pt site with the diazo N═N and ester carbonyl motifs plays a central role in controlling stereoselectivity, which is supported by density functional theory calculations.