Palladium‐Catalyzed Tandem Carbonylative Aza‐Wacker‐Type Cyclization of Nucleophile Tethered Alkene to Access Fused N‐Heterocycles

Abstract

Main observation and conclusion Although tandem reactions offer rapid access to structurally complex molecules in one‐pot reaction, the selectivity issue needs to be addressed particularly when incompatible step reactions are involved. Herein, we report the selective synthesis of fused N‐heterocycles from nucleophile‐tethered alkenylamide and carbon monoxide via palladium (Pd)‐catalyzed tandem carbonylative aza‐Wacker‐type cyclization. The electron‐deficient nature of amide N—H and the intramolecular coordination of Pd with alkene accelerate the aminopalladation and effectively prevent the side oxidative carbonylation of diamine moiety to form urea. It is also found that the reported acyl Pd chloride intermediate may not be involved in this tandem cyclization. This work not only provides an efficient synthetic route to fused 1,4‐diazepanones and 1,4‐diazepanes but also inspires further development of tandem reactions for the diverse synthesis of heterocycles.

Divergent Syntheses of Pyridoacridine Alkaloids viaPalladium‐Catalyzed Reductive Cyclization with Nitro‐Biarenes

“…The different reactive activity for the two substrates was rationalized by density functional theory (DFT) calculations, [ 12 ] and the distribution of Mulliken atomic charge [ 13 ] on carbon 8 of 5l (−0.657) showed higher electronic density than that on the corresponding carbon of 3h (−0.488) (Figure 2), which is favored for electrophilic cyclization process to form hydroxyl intermediate ( D in Scheme 2). By analogy with the previously reported mechanism [ 10b,11a ] and our expermental observation, a tentative mechanism was proposed with compound 5l : First, in the presenc of Mo(CO) 6 and phenanthroline, Pd(OAc) 2 converts to palladium CO complex A . Afterward, complex A reacts with the nitro‐ biarene 5l through single‐electron transfer and affords radical anion B .…”

“…[ 9 ] Carbon monoxide is the most frequently employed reductant due to good selectivity and atomic economy. [ 10 ] Recently, CO‐surrogates were developed to overcome the limitation of hazardous pressurized gas manipulation, [ 11 ] but most cases focus on the construction of 5‐membered ring containing heterocycles. As part of our efforts to develop N ‐heterocycle synthesis, we have demonstrated that palladium‐catalyzed reductive cyclization with Mo(CO) 6 can be successfully applied in nitroalkene system to afford indole alkaloids.…”

Palladium Iodide‐Catalyzed Selective Carbonylative Double Cyclization of 4‐(2‐Aminophenyl)‐3‐yn‐1‐ols to Dihydrofuroquinolinone Derivatives

“…[ 3 ] When the same palladium catalyst is capable to promote heterocyclization coupled with carbonylation, [ 4 ] formation of two new rings with incorporation of CO as a carbonyl function in a single synthetic operation may take place, with direct formation of carbonylated fused heterocycles. [ 1p‐q,5‐6 ]…”

Palladium‐Catalyzed anti‐Markovnikov Halosulfonamidation of Unactivated Alkene†

“…The palladium‐catalyzed aminative difunctionalization of alkenes to incorporate an amine group as well as another functional group has been employed as a robust methodology to construct highly functionalized alkylamines of high value in medicinal and material chemistry with benign efficiency in synthetic routine. [ 1‐7 ] When halogen is introduced in a position vicinal to a sulfonamide group, this halosulfonamidation not only results in improvements in biological applications of sulfonamide scafford, [ 8‐10 ] but also provides the platform for further transformations into various amine derivatives, e.g ., aziridines and diamines. [ 11‐18 ]…”