Scientists from the Zelinsky Institute have developed an approach to the synthesis of important heterocyclic compounds

Functionalized derivatives of malonic ester are widely used in the synthesis of complex carbocyclic compounds. Their advantages are the ease of preparation, as well as the preorganization of reactive fragments for cyclization due to the steric effect of two ester groups. Syntheses of cyclopentenes, dihydroindenes, cyclic enones, and other carbocycles have been successfully realized using disubstituted malonic esters. Unfortunately, methods for using malonates to assemble heterocycles are much less known.

Scientists from the Laboratory of Organic and Metal-Organic Nitrogen-Oxygen Systems of the Zelinsky Institute synthesized bis-oximinoalkyl derivatives of malonic esters for the first time. The proposed method for their preparation is based on the double Michael addition of nitrosoalkenes to malonates. The obtained compounds were introduced into the reaction of reductive cyclization on available heterogeneous catalysts. As a result, piperidine-4-carboxylates and indolizidinones were obtained — heterocyclic compounds that are actively used in medicinal chemistry and are difficult to access by other synthetic methods.

Source:

Evgeny V. Pospelov, Yaroslav D. Boyko, Sema L. Ioffe, Alexey Yu. Sukhorukov Synthesis of Bis(β-oximinoalkyl)malonates and Their Catalytic Reductive Cyclization to Piperidines. Adv. Synth. Catal., 2022, 364, 2557-2564. DOI: 10.1002/adsc.202200424.