Preliminary Study on Novel Expedient Synthesis of 5-Azaisocoumarins by Transition Metal-Catalyzed Cycloisomerization

Abstract

A preliminary study to develop a novel synthetic method for 3-aryl-5-azaisocoumarins was performed herein. The cycloisomerization of N -pyranonyl propargylamines in the AgOTf-catalyzed system efficiently afforded the desired 3-aryl-5-azaisocoumarins in a highly regioselective manner. This unprecedented method is expected as an expedient alternative synthetic route to 5-azaisocoumarins because the regioselectivity problem is circumvented, and it is easier to introduce substituents on the pyridine ring compared to previously reported intramolecular lactonization approaches.

Silver-catalyzed synthesis of nitrogen heterocycles: recent advancements

“…The plausible reaction route begins with the in situ generation of the imine 124 via silver-mediated conden- Synthesis of 5-azaisocoumarins 127 via a novel regioselective silver-catalyzed cycloisomerization reaction was put forward by Han and colleagues. 86 In comparison with previous conventional lactonization procedures that yielded a mixture of regioisomers, this was an outstanding alternative step-econ-omical strategy for the regioselective synthesis of 3-aryl-5-azaisocoumarins 127 in moderate yields. This protocol also offered easy derivatization of pyridine ring.…”

Synthesis of Proposed Structure of Aaptoline B via Transition Metal-Catalyzed Cycloisomerization and Evaluation of Its Neuroprotective Properties in C. Elegans

“…The NMR spectra were consistent with the previously reported data. Melting point: 74~76 °C; 1 H-NMR (500 MHz, CDCl3) δ 8.59 (s, 2H), 4.46 (q, 2H, J = 7.1 Hz), 2.63 (s, 3H), 1.43 (t, 3H, J = 7.1 Hz); 13 Recently, we have intensively worked on the synthesis and biological applications of pyridine-fused privileged scaffolds, such as quinoline and pyridocoumarin, using Ag(I)catalyzed cycloisomerization [8][9][10]. Taking advantage of its high yield and regioselectivity, Ag(I)-catalyzed cycloisomerization has also been used for the synthesis of natural products, including goniothalines [8] and polynemoraline C [10].…”