Organocatalytic enantioselective reaction of tertiary α-(7-indolyl)methanols with tryptamines

Abstract

With the aid of chiral phosphoric acid, enantioselective 1,6-addition of tryptamines to in situ formed alkynyl 7-methylene-7H-indoles from tertiary α-(7-indolyl)methanols has been established for the first time, furnishing a broad...

Organocatalytic asymmetric cascade bicyclization: access to chiral polycyclic bisindoles from 2-indolylmethanols and propargylic alcohols

“…Recently, we 4 and other groups 5 have developed α-indolyl propargylic alcohols as versatile platform molecules for the synthesis of indole derivatives. In our previous work, we achieved the catalytic asymmetric synthesis of bis(indolyl)methanes and indole-substituted allenes via 1,4- and 1,6-addition of α-indolyl propargylic alcohols, respectively.…”

Palladium-catalyzed stereoselective construction of chiral allenes bearing nonadjacent axial and two central chirality

“…A few asymmetric catalytic reactions have been developed to construct chiral allene derivatives bearing multiple adjacent stereocenters. 9 As for the more difficult stereoselective construction of allenes with multiple nonadjacent stereocenters, to the best of our knowledge, limited methodologies have been devised. In 2018, Trost and co-workers synthesized chiral exocyclic allenic compounds bearing nonadjacent axial and two central chiral centers through a palladium-catalyzed asymmetric [3 + 2] cycloaddition reaction.…”

Organocatalytic Enantioselective Nucleophilic Addition of Indole Imine 5-Methides

“…Depending on the positions of the exocyclic methide unit, IIMs have multiple topological isomers, namely, indole imine 2-, 3-, 4-, 5-, 6-, and 7-methides (Scheme ). ,− Among them, indole imine 2- and 3-methides (2- and 3-IIMs) have been most studied regarding their asymmetric transformations. ,, This is probably partly due to the short distance between the methide position and the imine motif and the typical catalytic activation site, which permits relatively easy stereocontrol. In contrast, other topological isomers, such as 4-, 6-, and 7-IIMs, have been much less explored for asymmetric synthesis since remote stereocontrol is often required in these cases in order to achieve high enantioselectivity. − While sporadic examples are known for these isomers, 5-IIM is the only isomer whose asymmetric transformations remain unknown, to the best of our knowledge.…”

“… ,− Among them, indole imine 2- and 3-methides (2- and 3-IIMs) have been most studied regarding their asymmetric transformations. ,, This is probably partly due to the short distance between the methide position and the imine motif and the typical catalytic activation site, which permits relatively easy stereocontrol. In contrast, other topological isomers, such as 4-, 6-, and 7-IIMs, have been much less explored for asymmetric synthesis since remote stereocontrol is often required in these cases in order to achieve high enantioselectivity. − While sporadic examples are known for these isomers, 5-IIM is the only isomer whose asymmetric transformations remain unknown, to the best of our knowledge. Indeed, among all these topological isomers, 5-IIM has the longest distance between the methide and imine motifs, which poses a substantial challenge to effective stereocontrol by the catalyst.…”

“…We employed racemic indol-5-ylmethanol 1a as the model precursor to 5-IIM and 2-phenyl-1 H -pyrrole ( 2a ) as the nucleophile for the initial study (Table ). Chiral phosphoric acids (CPAs) were evaluated as potential catalysts for this reaction, considering their general excellent performance in the asymmetric transformations of other IIMs and the related aza- para -quinone methides. ,− With the well-known TRIP catalyst ( A1 ), the reaction in DCM proceeded successfully at room temperature to form the desired product 3a in 58% yield, albeit with only a 76:24 enantiomeric ratio (er, entry 1). These results implied that the remote enantiocontrol was indeed challenging.…”