Selective C(sp³)–H Cleavage of Enamides for Synthesis of 2-Pyridones via Ligand-Enabled Ni–Al Bimetallic Catalysis

Abstract

Previously reported direct C–H functionalization reactions of enamides mainly occurred at vinylic C­(sp2)–H bonds because of their relatively high reactivity, while less reactive β′-C­(sp3)–H activation has been rarely explored. Herein we report a selective C­(sp3)–H cleavage of N-formyl enamides without backbone modification, providing a series of 2-pyridones in 58–99% yields. A bifunctional phosphine oxide (PO) ligand-bridging Ni–Al bimetallic catalyst played key role in the reaction.

Bimetallic anchoring catalysis for C-H and C-C activation

“…Despite an efficient method, the requirement of an ester directing group greatly restricts the scope of substrates and the complexity of products. With the use of taddol-derived phosphine oxide (PO 6 ) ligand-ligated Ni−Al bimetallic catalyst, Ye's group [45] recently achieved selective β′-C(sp 3…”

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…It is also applied as a powerful catalyst in polymerization [249,250], C-C coupling [251], oxygen [252] or hydrogen evolution [253], or even cycloaddition reactions [254]. Its accessibility and high catalytic activity have been well-explored also in C-H activation processes [255][256][257][258][259]. Some of the discoveries led to the formation of important biologically active substances that play a crucial role in pharmaceutical studies, as exemplified by a work published by Ackermann and co-workers in 2019 [260].…”

Base‐Promoted Synthesis of 3‐Alkenyl‐2‐pyridones from N‐Propargyl‐β‐enaminones and Aryl Aldehydes

“…Traditionally, the synthetic method of these motifs is mainly through the condensation of amines/amides with carbonyl compounds. [ 6 ] The transition metal‐catalyzed [4+2] cyclization reactions of amides with terminal alkynes [ 7 ] and [2+2+2] cyclization reactions of isocyanates with alkynes [ 8 ] were another powerful approach to make pyridones. However, the abovementioned methods still have some limitations, such as poor substrate scope, requirement of noble metal as catalysts, and involvement of toxic and hazardous chemicals.…”