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

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 (Pt-1/CeO2), in conjunction with the alcoholysis of ammonia borane, promotes exceptionally E-selective hydrogenation of alpha-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 alpha-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 N-15-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.