Catalytic Asymmetric Arylation of 3‐Indolylmethanols: Enantioselective Synthesis of 3,3′‐Bis(indolyl)oxindoles with High Atom Economy

Abstract

The catalytic enantioselective arylation of 3‐indolylmethanols has been established in an atom‐economic fashion, which assembles isatin‐derived 3‐indolylmethanols and 3‐methylindoles into biologically important 3,3′‐bis(indolyl)oxindoles bearing a quaternary stereogenic center in high yields and good enantioselectivities (≈99 % yield and 91:9 enantiomeric ratio). This reaction also represents the catalytic enantioselective synthesis of 3,3′‐bis(indolyl)oxindoles, which is applicable to a wide range of substrates, yielding a series of chiral 3,3′‐bis‐ (indolyl)oxindoles with structural diversity. Control experiments demonstrated that the NH group in the indole moiety of 3‐indolylmethanol is important in obtaining good enantioselectivity, whereas the NH group of 3‐methylindole plays a crucial role in the reactivity via the hydrogen bonding interaction with the catalyst.

Organocatalyzed Asymmetric Friedel‐Crafts Reactions: An Update

“…Notably, there might be two probable reaction paths for the reaction. One is that the indole‐C2 position directly attacks the o ‐quinone methide intermediate via acidic conditions; another is that the indole‐C3 position attacks the o ‐quinone methide intermediate to make a dearomatized intermediate compound and then attacks to the indole‐C2 situation through acidic conditions . Although, during the reaction method, no dearomatized indole products (provided by the attack of indole‐C3 situation to o‐quinone methide intermediate) have been detected.…”

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

“…Ma and co-workers described the CPA (cat. 32 )-catalyzed enantioselective decarboxylative alkylation of β-keto acids with 3-hydroxy-3-indolyloxindoles, affording the 3-functionlized 3-indolyloxindoles bearing an all-carbon quaternary stereocenter in good yields (up to 98% yield) and with excellent enantioselectivities (up to 99% ee, Scheme 50 ) [ 67 ]. The reactions showed good tolerance to various aromatic and aliphatic β-keto acids as well as substituted 3-hydroxy-3-indolyloxindoles.…”

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.…”