Design and Catalytic Asymmetric Construction of Axially Chiral 3,3′‐Bisindole Skeletons

Abstract

The first catalytic asymmetric construction of 3,3′‐bisindole skeletons bearing both axial and central chirality has been established by organocatalytic asymmetric addition reactions of 2‐substituted 3,3′‐bisindoles with 3‐indolylmethanols (up to 98 % yield, all >95:5 d.r., >99 % ee). This reaction also represents the first highly enantioselective construction of axially chiral 3,3′‐bisindole skeletons, and utilizes the strategy of introducing a bulky group to the ortho‐position of prochiral 3,3′‐bisindoles. This reaction not only provides a good example for simultaneously controlling axial and central chirality in one operation, but also serves as a new strategy for catalytic enantioselective construction of axially chiral 3,3′‐bisindole backbones from prochiral substrates.

Conversion of two stereocenters to one or two chiral axes: atroposelective synthesis of 2,3-diarylbenzoindoles

“…Later, Kamikawa, Takahashi and Ogasawara reported an enantioselective desymmetrising ring-closing metathesis strategy to prepare axially chiral indole N -aryl compounds 19. Very recently, Shi and Tan independently reported a well-designed chiral phosphoric acid-catalyzed asymmetric synthesis of indol C(3)-aryl axial chirality;20 Gu reported Pd-catalyzed dynamic kinetic intramolecular C–H cyclization to construct indol C(3)-aryl atropisomers 21. However, no studies have been reported on the synthesis of indol C(2)-aryl axial chirality.…”

Brønsted Acid‐Catalysed Dehydrative Substitution Reactions of Alcohols

“…Furthermore, the use of a sterically demanding tertiary alcohol within 47 is essential for the regioselectivity of addition, with the analogous secondary benzylic alcohol undergoing selective reaction at the carbinol centre to form a racemic product. This work has subsequently been extended to the synthesis of highly substituted 3,3′‐bisindole products such as 51 from 3‐hydroxy‐3‐indolyloxindoles 50 (Scheme 25 b), [58] with excellent control of both axial and point chirality for a range of examples.…”

New Perspectives in the Indole Ring Functionalization using 2‐Indolylmethanols

“…Following a similar procedure, more complex and structurally rigid derivatives embedding four indole structures can be obtained by a three‐component reaction involving 2‐indolylmethanol 84 , indole and bisindoles 85 (Scheme ) . The 3,3′‐bisindolyl derivative primarily formed reacts with the alkylideneindolenine intermediate generated upon dehydration of 85 ( cf .…”