Synthesis of N‐Heterocycles by Dehydrogenative Annulation of N‐Allyl Amides with 1,3‐Dicarbonyl Compounds

Abstract

Dehydrogenative annulation under oxidizing reagent-free conditions is an ideal strategy to construct cyclic structures. Reported herein is an unprecedented synthesis of pyrrolidine and tetrahydropyridine derivatives through electrochemical dehydrogenative annulation of N-allyl amides with 1,3-dicarbonyl compounds. The electrolytic method employs an organic redox catalyst, which obviates the need for oxidizing reagents and transition-metal catalysts. In these reactions, the N-allyl amides serve as a four-atom donor to react with dimethyl malonate to give pyrrolidines by a (4+1) annulation, or with β-ketoesters to afford tetrahydropyridine derivatives by a (4+2) annulation.

Catalyst‐Free Decarboxylation of Carboxylic Acids and Deoxygenation of Alcohols by Electro‐Induced Radical Formation

“…Meanwhile, electrochemistry has experienced a renaissance in recent years. Major advances on cross coupling, annulation, dehydrogenation, and other diverse reactions have been accomplished by different groups . However, conjugate addition from RAEs and oxalates were rare under catalyst‐free and mild electrochemical conditions.…”

“…4) Undero pen air conditions, the yield is slightly diminished (entry 12), indicating that this reaction is insensitivet om oisture and there is no requirement for the strict exclusiono fo xygen. 5) An electric current is essential for this transformation,a nd visible light [12] is not critical in the reaction(entries [13][14][15].…”

“…[3f-h, 12] Therefore, the development of catalyst-free and robustsynthetic methods to generate radicals for synthetic application is still in high demand.Meanwhile, electrochemistry has experienced ar enaissance in recent years. Major advances on cross coupling, [13] annulation, [14] dehydrogenation, [15] and other diverse reactions [16] have been accomplished by different groups. [17] However,c onjugate addition from RAEs and oxalates were rare under catalyst-free and mild electrochemical conditions.…”

“…In the dark 85 15 [c] Under 450 nm irradiation,n oc urrent 53 Excellent compatibility for ab road scope of secondary and tertiarya lkyl RAEs bearing different functional groups was demonstrated (14)(15)(16)(17)(18)(19)(20)(21)(22)u nder standard conditions (Scheme 1C).…”

A Green Approach: Vicinal Oxidative Electrochemical Alkene Difunctionalization

“…In 2018, Xu and co‐workers proposed a first synthesis of pyrrolidines and tetrahydropyridines derivatives by N‐allyl amides annulation with 1,3‐dicarbonyl compounds in yields of up to 89 % (Scheme ). The N‐allyl amides react with the malonate through annulation (4+1) providing pyrrolidines, or β‐ketoesters to give tetrahydropyridine derivatives via annulation (4+2).…”