Rh(III)-Catalyzed Asymmetric Synthesis of Axially Chiral Biindolyls by Merging C–H Activation and Nucleophilic Cyclization

Abstract

Enantiomeric access to pentatomic biaryls is challenging due to their relatively low rotational barrier. Reported herein is the mild and highly enantioselective synthesis of 2,3′-biindolyls via underexplored integration of C−H activation and alkyne cyclization using a unified chiral Rh(III) catalyst. The reaction proceeded via initial C−H activation followed by alkyne cyclization. A chiral rhodacyclic intermediate has been isolated from stoichiometric C−H activation, which offers direct mechanistic insight.

Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies

“…Introduction of ortho Me and Cl groups was also tolerated (14 and 15), thus suggesting compatibility with the steric effect of the arene.Afew meta-substituted arene substrates coupled regioselectively with 2a at the less hindered ortho site in excellent enantioselectivity (> 97 % ee). Thescope of the cyclopropenyl alcohol was next examined in the coupling with arene 1a.Introduction of various electrondonating (OMe,O Ph, OBn), electron-withdrawing (CF 3 , OCF 3 ), and halogen groups into the para position of the alcohol phenyl ring was fully tolerated, with the enantioselectivity ranging from 89 %t o9 6% ee (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Comparably excellent enantioselectivity and good efficiencyw ere also realized for those alcohols bearing ortho and meta substituents (33-40), which is indicative of tolerance of steric and electronic perturbation.…”

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.…”

Rhodium(III)‐Catalyzed Enantio‐ and Diastereoselective C−H Cyclopropylation of N‐Phenoxylsulfonamides: Combined Experimental and Computational Studies

“…A stoichiometric reaction of 1 a and ( R )‐ Rh4 led to the isolation of rhodacycle 57 as the enantiometrically and diastereomerically pure product (Scheme b), which was characterized by NMR spectroscopy and mass spectrometry. Designation of 57 as a catalyst for the coupling of 1 a and 2 a afforded ( S , S )‐ 3 in 68 % yield and 95 % ee , thus indicating that the reaction follows a C−H activation pathway and the chiral environment in 57 offers sufficient control of the enantioselectivity …”