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

Cuibo Liu, Zhongxin Chen, Huan Yan, Shibo Xi, Kah Meng Yam, Jiajian Gao, Yonghua Du, Jing Li, Xiaoxu Zhao, Keyu Xie, Haisen Xu, Xing Li, Kai Leng, Stephen J. Pennycook, Bin Liu, Chun Zhang, Ming Joo Koh, Kian Ping Loh

Research output: Journal article publicationJournal articleAcademic researchpeer-review

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbereaay1537
JournalScience advances
Volume5
Issue number12
DOIs
Publication statusPublished - 6 Dec 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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