Thiourea-Catalyzed Enantioselective Malonate Addition onto 3-Sulfonyl-3′-indolyl-2-oxindoles: Formal Total Syntheses of (−)-Chimonanthine, (−)-Folicanthine, and (+)-Calycanthine

Abstract

A general approach to bispyrroloindolines via a key thiourea-catalyzed addition of malonates to 3-sulfonyl-3′-indolyl-2-oxindoles is reported. The enantioselelective process is found to be highly effective (up to 94% ee), where a C–C bond formation leads to the synthesis of a number of 2-oxindoles with an all-carbon quaternary stereocenter.

Asymmetric Organocatalytic Conjugate Addition of Electron‐Rich Phenols and 1,3‐Dicarbonyls to Arylsulfonyl Indoles in an Oil‐Water Biphasic System

“…The unprotected isatin 1b also showed good tolerance to this reaction and gave the products 6b in good yield and excellent enantioselectivity (Table , entry 2). In Bisai′s studies, the unprotected sulfonylindole 1b delivered the corresponding product 6b in 52 % yield and 40 % ee after 52 h reaction time in organic solvent systems . However, in our optimal water‐oil conditions, the product 6b was obtained in 45 % yield and >99 % ee after 18 h. This result provided strong support that water was an essential component for accelerating the reaction rate and improving the enantioselectivity.…”

“…1,3‐dicarbonyl compounds, such as diketones and keto esters, are commonly used as ideal nucleophiles in the asymmetric Michael addition and domino reactions . Very recently, Bisai and co‐workers reported an enantioselective thiourea‐catalyzed addition of malonates to sulfonylindoles 1 in organic solvent systems and apply the method for enantioselective synthesis of dimeric cyclotryptamine alkaloids . However, only limited substrate scope was examined and unprotected sulfonylindole 1c gave low reactivity and enantioselectivity.…”

Recent Advances in Natural Products Synthesis Using Bifunctional Organocatalysts Bearing a Hydrogen‐Bonding Donor Moiety

“…In 2018, formal total syntheses of dimeric HPIs based on enantioselective addition reaction were reported by Bisai and co‐workers (Scheme ) . They developed an enantioselective addition reaction of dibenzyl malonate 59 to 3‐sulfonyl oxindole 60 in the presence of quinidine‐derived thiourea bifunctional organocatalyst 58 (10 mol%), and obtained the malonate adduct 61 in 85% yield with 94% ee.…”

Enantioselective synthesis of mixed 3,3′-bisindoles via a phosphine-catalyzed umpolung γ-addition of 3′-indolyl-3-oxindoles to allenoates

“…From a synthetic viewpoint, preparation of optically enriched mixed 3,3 0 -bisindole structures is a long-standing and challenging task, especially in view of the presence of an all-carbon quaternary stereogenic center at the indole C 3 -position [15][16][17][18][19][20]. In recent years, various synthetic strategies have been developed for their asymmetric synthesis, including: 1,4-conjugate additions or epoxide-opening via Friedel-Crafts reactions of indoles [21][22][23][24], Rh-or Ru-mediated multicomponent tandem reactions [25][26][27], as well as nucleophilic substitutions of various 3-indolylmethanols and their structural analogues [28][29][30][31][32][33][34][35][36]. Undoubtedly, given the extreme synthetic value of the mixed 3,3 0 -bisindole motifs, there still exists an urgent need to devise efficient approaches for their enantioselective synthesis, especially those methods amenable for the preparation of a broad spectrum of natural products.…”

“…The 3 0 -indolyl-3-oxindoles appear to be ideal prochiral pronucleophiles, the hydrogen atom at the oxindole 3-position is sufficiently acidic for basic abstraction, thus allowing for subsequent reactions to take place. The reactivity inversion of substrates is appealing: 3 0 -indolyl-3oxindoles serve as a nucleophilic partner, as opposed to many existing methods [28][29][30][31][32][33][34][35][36] employing leaving group-bearing 3,3 0bisindoles as an electrophile. Moreover, in addition to allenoates, other electrophilic partners could also be utilized, therefore greatly broadening the reaction scope, making a diverse range of target molecules synthetically accessible.…”