Organocatalytic asymmetric arylation of indoles enabled by azo groups

Abstract

Arylation is a fundamental reaction that can be mostly fulfilled by electrophilic aromatic substitution and transition-metal-catalysed aryl functionalization. Although the azo group has been used as a directing group for many transformations via transition-metal-catalysed aryl carbon-hydrogen (C-H) bond activation, there remain significant unmet challenges in organocatalytic arylation. Here, we show that the azo group can effectively act as both a directing and activating group for organocatalytic asymmetric arylation of indoles via formal nucleophilic aromatic substitution of azobenzene derivatives. Thus, a wide range of axially chiral arylindoles have been achieved in good yields with excellent enantioselectivities by utilizing chiral phosphoric acid as catalyst. Furthermore, highly enantioenriched pyrroloindoles bearing two contiguous quaternary chiral centres have also been obtained via a cascade enantioselective formal nucleophilic aromatic substitution-cyclization process. This strategy should be useful in other related research fields and will open new avenues for organocatalytic asymmetric aryl functionalization.

Organocatalytic Asymmetric Annulation of ortho‐Alkynylanilines: Synthesis of Axially Chiral Naphthyl‐C2‐indoles

“…More importantly, as shown in Scheme b, if a chiral environment can induce axis rotation of the newly generated C2‐substituted indoles, the enantioselective construction of axially chiral aryl‐C2‐indole skeletons through the annulation of ortho ‐alkynylanilines could be realized. This strategy is different from the current reports by the research groups of Shi, Gu, Tan, and Li, in which readily available or in situ generated indole skeletons are starting materials for the synthesis of axial chirality between the aromatic rings and C3‐substituted indoles (Scheme c). The above‐mentioned reaction design for introducing a new route to axially chiral aryl‐C2‐indole skeletons potentially has broad applications, but several challenges need to be addressed.…”

Sequential MCR via Staudinger/aza-Wittig versus Cycloaddition Reaction to Access Diversely Functionalized 1-amino-1H-imidazole-2(3H)-thiones

“…ppm; 13 C-NMR (100 MHz, DMSO-d6) δ 8.9, 27.6, 27.8, 35.9, 80.8, 116.2, 128.2, 153.8, 160.2, 162.9 ppm; IR (Nujol, ν, cm −1 ): 3188, 3115, 1741, 1645, 1607; MS m/z (ESI): 301.15 (M + H) + ; calcd. for C12H20N4O3S (300.38): C, 47.98; H, 6.71; N, 18.65; found: C, 48.11; H, 6.63; N, 18.57.The partition of some signals here, as well as in the following cases, is due to the N1-amide rotameric effect[26].…”

Organocatalytic Enantioselective α‐Amination by Conjugate Addition of 5H‐Thiazol‐4‐ones to Arylazocarboxylates: Access to Chiral N,S‐acetals

“…Using arylazocarboxylates as electrophiles, Tan et al. elegantly achieved the asymmetric arylation of indoles, 2‐naphthols and 2‐naphthylamine (Scheme A) . Furthermore, they also found arylazocarboxylates could act as C−C−N synthons to form axially chiral aniline‐indoles .…”