Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles

Abstract

The first copper-catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.

Catalytic Oxidative Coupling Cyclization for Construction of Benzofuroindolenines under Mild Reaction Conditions

“…[1] Diverse elegant methods extensively complemented the fields of traditional coupling reactions and provided widely applicable approaches for new bond formation. [2] Efficient oxidative coupling protocols for functionalized indoles have been developed by the groups of Harran, [3] Danishefsky, [4] Trost, [5] Nicolaou, [6] Overman, [7] Muniz, [8] MacMillan, [9] Xiao, [10] Lei, [11] Vincent, [12] You, [13] Stephenson, [14] and others. [15] While, the synthetic utility of catalytic oxidative coupling cyclization for construction of complex benzofuroindolenines has not been fully developed.…”

Highly Diastereo‐ and Enantioselective Synthesis of Tetrahydro‐5H‐Indolo[2,3‐b]quinolines through Copper‐Catalyzed Propargylic Dearomatization of Indoles

“…Over the past decades, great progress has been made on the Ru‐ and Cu‐catalyzed propargylic substitution reactions via the metal‐allenylidene complexes . As our ongoing efforts towards the development of catalytic asymmetric dearomatization reactions, we envisioned that a copper‐catalyzed asymmetric propargylic dearomative [4+2] cycloaddition of simple substituted indoles with a copper‐allenylidene amphiphilic intermediate would afford the tetracyclic core structure of indole alkaloids communesins A‐H and perophoramidine (Scheme ). Of particular note, Xiao and co‐workers successfully disclosed the first copper‐catalyzed asymmetric propargylic formal [4+1] cycloaddition reaction with sulfur ylides .…”

Palladium(0)‐Catalyzed Intermolecular Asymmetric Cascade Dearomatization Reaction of Indoles with Propargyl Carbonate

“…Further evaluation of the concentration( entries 7-11) of 1a revealed that c = 0.2 mol L À1 was optimal in terms of yield (entry 8). Pd 2 (4-OMe-dba) 3 was ab etter palladium source than Pd 2 dba 3 and [Pd(allyl)Cl] 2 (entries 12 and 13). [10] Furthermore, some additives were tested.…”

“…[2] Notably,t ransitionmetal-catalyzed allylic dearomatization reactions of indoles have witnessed significant progresses in the past decade. [3,4,5] Recently,w er ealized the construction of fused indolenine skeletons in ac ascadef ashion. [6] In 2014, the Rawal group and we independently reported an intermolecular cascade dearomatization reactiono fi ndole-based bisnucleophiles with propargyl carbonate, leading to aseries of spiroindolenines andspiroindolines.…”

“…To our delight, both yield and 3a/4a ratio were improvedr emarkably when 4 molecular sieves were used (82 %y ield, 95 % ee, > 19:1 3a/4a, entry 15). Finally,t he optimized reactionc onditions were establisheda st he following:P d 2 (4-OMe-dba) 3 (2.5 mol %), L1 (11mol %), 4 MS (100 mg) in DMA (1 mL) at 80 8C( entry 15). Notably, 4a could not be converted to 3a under the optimized conditions, suggesting the formation of CÀNislikely an irreversible process here.…”