Cobalt(III)-Catalyzed Regioselective C6 Olefination of 2-Pyridones Using Alkynes: Olefination/Directing Group Migration and Olefination

Abstract

Co(III)-catalyzed highly regio-and stereoselective direct C6 olefination of 2-pyridones with alkynes has been developed with the assistance of chelation. Upon variation of the reaction conditions, 2-pyridones react well with diaryl alkynes via a C6 olefination/directing group migration pathway to give the tetrasubstituted 6-vinyl-2-pyridones, but the C6−H olefination with terminal alkynes works effectively to afford only the C6-olefinated 2-pyridones. A judicious choice of a solvent and an additive is crucial for catalysis. The protocols feature 100% atom economy, excellent site selectivity, high stereoselectivity, an ample substrate scope, and good compatibility of functional groups. Synthetic applications are demonstrated, and experimental studies and density functional theory calculations are conducted to gain mechanistic insight into the two transformations.

Recent Advances in the High‐Valent Cobalt‐Catalyzed C−H Functionalization of N‐Heterocycles

“…Ravikumar and coworkers were able to detect five‐membered and seven‐membered cobaltacycle intermediate in ESI‐HRMS [69] . Xu and Lei group further extended their methodology for late‐stage modification using estrone derived alkyne to design corresponding product in excellent yield [70] …”

“…[69] Xu and Lei group further extended their methodology for late-stage modification using estrone derived alkyne to design corresponding product in excellent yield. [70] In continuation of our research interest in remote functionalization of heterocycles, we developed a protocol for the direct C8-olefination of isoquinolone (105) using terminal alkynes (53). In this strategy, instead of installing a directing group at adjacent position.…”

CpXCo(III)‐catalyzed selective C–H alkenylation of indoles with ethynylethylene carbonates

“…[ 16 ] In 2021, Lei's group reported the Co(III)‐catalyzed direct alkenylation of 2‐pyridones with alkynes at the C‐6 position with high regioselectivity. [ 17 ] The vast majority of terminal alkynes reported to date have been used for 2,1‐insertion. However, 1,2‐insertion is still very rare and largely unexplored.…”

Chemo-, Regio-, and Stereoselective Assembly of Polysubstituted Furan-2(5H)-ones Enabled by Rh(III)-Catalyzed Domino C–H Alkenylation/Directing Group Migration/Lactonization: A Combined Experimental and Computational Study

“…However, it still suffers from unsatisfactory atom-economy as water, alcohol, amide, or carboxylic acid are produced as byproducts, even though recently several breakthroughs involving the intramolecular migration of the broken fragment from the cleavage of N–O, N–N, or O–O bonds have been made through the relatively complicated modification of the coordination environment and saturation of the TM center . Evidently, it is quite fascinating but also challenging to achieve the DG-mediated redox-neutral C–H activation and subsequent migration cascade to meet the concept of “green and sustainable” C–H functionalization (Scheme b), ,− ,− especially via the formal cleavage of more stable chemical bonds such as C–C/N/O bonds and in situ formation of multiple new bonds. Indeed, such a strategy could simultaneously increase the diversity of the products in a step-/atom-economic fashion.…”