Expedient synthesis of <i>E</i>-hydrazone esters and 1<i>H</i>-indazole scaffolds through heterogeneous single-atom platinum catalysis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31840074.
- Also identified by DOI 10.1126/sciadv.aay1537 and PMC identifier 6897547.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Unprotected <i>E</i>-hydrazone esters are prized building blocks for the preparation of 1<i>H</i>-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 CeO<sub>2</sub> nanorods (Pt<sub>1</sub>/CeO<sub>2</sub>), in conjunction with the alcoholysis of ammonia borane, promotes exceptionally <i>E</i>-selective hydrogenation of α-diazoesters to afford a wide assortment of <i>N</i>-H hydrazone esters with an overall turnover frequency of up to 566 hours<sup>-1</sup> 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 1<i>H</i>-indazole-derived pharmaceuticals and their <sup>15</sup>N-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.