Synthesis of Bis(β‐Oximinoalkyl)malonates and Their Catalytic Reductive Cyclization to Piperidines

Synthesis of Bis(β‐Oximinoalkyl)malonates and Their Catalytic Reductive Cyclization to Piperidines Full article

Journal

Advanced Synthesis & Catalysis
ISSN: 1615-4169 , E-ISSN: 1615-4150

Output data

Year: 2022, Volume: 364, Number: 15, Pages: 2557-2564 Pages count : 8 DOI: 10.1002/adsc.202200424

Authors

Pospelov Evgeny V. ^1,2 , Boyko Yaroslav D. ³ , Ioffe Sema L. ¹ , Sukhorukov Alexey Yu. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, 119991, Leninsky prospect, 47, Moscow, Russia
2	Department of Chemistry, M. V. Lomonosov Moscow State University, 119991, Leninskie gory, 1, str. 3, Moscow, Russia
3	UIUC: Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois, 61801 United States

Hitherto unknown bis(β-oximinoalkyl)malonates were demonstrated to be convenient platforms for the synthesis of saturated N-heterocycles. Upon heterogeneous catalytic hydrogenation, these dioximes undergo reductive cyclization to give substituted piperidine-4,4’-dicarboxylates, which are valuable building blocks in medicinal chemistry. By using dioximes bearing an additional ester group in the side chain, tandem piperidine/pyrrolidinone ring closure leading to indolizidinone framework was showcased in this work. A modular synthesis of initial bis(β-oximinoalkyl)malonates (both symmetrically and unsymmetrically substituted) was accomplished via a sequential Michael addition of two nitrosoalkene molecules to malonic ester. The mechanism of the reductive cyclization of dioximes to piperidines was investigated by isotope scrambling experiments and isolation of intermediates.

Pospelov E.V. , Boyko Y.D. , Ioffe S.L. , Sukhorukov A.Y.
Synthesis of Bis(β‐Oximinoalkyl)malonates and Their Catalytic Reductive Cyclization to Piperidines
Advanced Synthesis & Catalysis. 2022. V.364. N15. P.2557-2564. DOI: 10.1002/adsc.202200424 WOS Scopus OpenAlex

Web of science:	WOS:000823282000001
Scopus:	2-s2.0-85133796364
OpenAlex:	W4283461386

DB	Citing
OpenAlex	10
Scopus	9
Web of science	9