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

Cuibo LiuZhongxin ChenHuan YanShibo XiKah Meng YamJiajian GaoYonghua DuJing LiXiaoxu ZhaoKeyu XieHai-Sen XuXing LiKai LengStephen John PennycookBin LiuChun ZhangMing Joo KohKian Ping Loh
Published in: Science advances (2019)
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.
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