α-Oxocarboxylic Acids as Three-Carbon Insertion Units for Palladium-Catalyzed Decarboxylative Cascade Synthesis of Diverse Fused Heteropolycycles

Abstract

A novel palladium-catalyzed decarboxylative cascade cyclization for the assembly of diverse fused heteropolycycles by employing α-oxocarboxylic acids as three-carbon insertion units is reported. This protocol enables the synthesis of isoquinolinedione-and indolo[2,1-a]isoquinolinone-fused benzocycloheptanones in moderate to good yields by the use of different aryl iodides, including alkene-tethered 2-iodobenzamides and 2-(2-iodophenyl)-1H-indoles. Notably, the approach achieves simultaneous construction of both six-and seven-membered rings via sequential intramolecular carbopalladation, C−H activation, and decarboxylation.

Pd-Catalyzed C–H Functionalization of Indole-Containing Alkene-Tethered Aryl Halides with Alkynes To Construct Indole Alkaloid Scaffolds

“…On the basis of the above results and previous reports, , a possible mechanistic pathway for this transformation was outlined in Scheme . Initially, the catalytic cycle starts with the oxidative addition of Pd(0) to the C–I bond to form aryl–Pd­(II) intermediate A , which preferentially undergoes an intramolecular Heck cyclization and generates a primary alkylpalladium species B .…”

“…16f,j However, to the best of our knowledge, a transition-metal-catalyzed cascade C−H functionalization of indole-containing alkene-tethered aryl halides with alkynes has not been developed. Inspired by the above reports and our interest in palladium catalyzed cascade chemistry, 17 we assume that the internal alkyne can be incorporated as an effective C2 synthon into a five-membered palladacycle intermediate, which may be easily formed from an indole-containing alkene-tethered aryl halide through a sequential intramolecular carbopalladation and C−H activation process, resulting in a series of fused polycyclic skeletons 18 We began our study by investigating the reaction with 1…”

“…Herein, we describe our recent discovery on the Pd-catalyzed C–H functionalization of indole-containing alkene-tethered aryl halides with alkynes for the rapid assembly of various indole alkaloid scaffolds. It is noteworthy that Liang et al have recently reported a Pd-catalyzed decarboxylative cascade cyclization of alkene-tethered 2-(2-iodophenyl)-1 H -indoles with 2-oxocarboxylic acids leading to several indole alkaloid derivatives …”

Research advances in palladium-catalysed intermolecular C–H annulation of aryl halides with various aromatic ring precursors

“…Subsequently, our group and others designed various halogenated carboxylic acids as C1, C2 or C3 insertion units to construct different size-ring fused cyclic compounds via this strategy. [53][54][55][56][57][58][59][60][61][62] In these reactions, it was observed that the inser- tion of carboxylic acids usually showed good regioselectivity. Thus, the methods used o-halobenzoic acids, arynes and aryl halides as aromatic ring precursors, which could be complementary.…”

Synthesis of Spiroindenyl-2-Oxindoles through Palladium-Catalyzed Spirocyclization of 2-Bromoarylamides and Vinyl Bromides

“…The alkylpalladium II species can cleave C-H bonds of an aryl group tethered to the alkene moiety to generate C,C-palladacycles. The palladacycles may undergo intramolecular cyclization [24][25][26][27][28][29][30][31][32][33][34][35] or be captured with external reagents [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. These types of reactions not only represent a novel strategy to activate C-H bonds that are not in proximity to directing groups, but also provide easy access to complex polycyclic compounds.…”