Pd-Catalyzed N–H or C–H Functionalization/Oxidative Cyclization for the Efficient Synthesis of N-Aryl-Substituted [3,4]-Fused Pyrrolo­coumarins

Abstract

Abstract1-Aryl-2-methyl- or 3-methylchromeno[4,3-b]pyrrol-4(1H)-ones have been synthesized in excellent yields by the Pd-catalyzed intramolecular aza-Wacker-type cyclization of 3-allyl-4-arylaminocoumarins or C–H insertion/oxidative cyclization of N-allyl-N-aryl-4-aminocoumarins, respectively, in the presence of Cu(OAc)2 in acetic acid under heating. The starting allylcoumarins have been prepared by the allylation of 4-arylaminocoumarins with allyl bromide in CH3CN in the presence of Cs2CO3 at room temperature. Preliminary biological tests indicated interesting antioxidant activity and significant levels of inhibition of soybean lipoxygenase.

An Overview of the Synthesis of 3,4-Fused Pyrrolocoumarins of Biological Interest

“…One-pot reaction of 46 with 47c afforded compound 49c in 80% yield (Scheme 16). 4-Acylamino-and 4-ketalaminocoumarin derivatives 48a-h were synthesized from the reaction of 4-chlorocoumarin (46) with acylamine chlorohydrates or ketalamines 47a-h under treatment with Et3N in refluxing ethanol. Scheme 16.…”

“…Scheme 16. Synthesis of [1] benzopyrano [4,3-b]pyrrol-4(1H)-ones 17a,b, 49a-e from 4-chlorocoumarin (46).…”

“…The N(α)-(2oxo-2H-1-benzopyran-4-yl) Weinreb α-aminoamides (52a-f) were prepared in 73-87% Scheme 16. Synthesis of [1] benzopyrano [4,3-b]pyrrol-4(1H)-ones 17a,b, 49a-e from 4-chlorocoumarin (46).…”

“…Fused coumarins possess also biological activities, and many of them, like furocoumarins [ 33 , 34 ], pyranocoumarins [ 35 ] or pyridocoumarins [ 36 ] are isolated from nature. Fused pyrrolocoumarins display interesting biological properties, such as cytotoxic [ 37 , 38 , 39 , 40 , 41 , 42 ], antibacterial [ 42 ], anti-HIV [ 37 , 42 , 43 , 44 , 45 ], multidrug resistance reversal (MDR) [ 37 , 42 , 45 ], antibiotic [ 42 ], antioxidant [ 42 , 46 , 47 ], antitumor [ 45 ], and anti-inflammatory activities [ 42 , 46 , 47 ]. Some of them act also as benzodiazepine receptor (BZR) ligands [ 48 , 49 ], angiogenesis inhibitors [ 50 ], DYRK1A inhibitors [ 45 , 51 ], Wnt signaling inhibitors [ 52 ] or fluorescent probes for live cell imaging [ 53 ].…”

Pd-catalyzed oxidative amination of 2-alkenylquinazolin-4(3H)-ones: synthesis of methylene and vinyl derivatives of pyrrolo(pyrido)[2,1-b]quinazolinones

“…1). 3 The latter can undergo various conversions depending on the substrate structure and reaction conditions, leading to oxidative amination (intramolecular aza-Wacker cyclization), 4 carboamination, 5 tandem cyclization 6 and difunctionalization reactions. 7 As far as aza-Wacker cyclization is concerned, intermediate III undergoes β-hydride elimination yielding cyclic enamine structures IV ; under Pd( ii ) catalysis, this reaction pathway predominates over the protonolysis of intermediate III to hydroamination products V (Fig.…”