Stereodivergent synthesis of enantioenriched azepino[3,4,5-cd]-indoles via cooperative Cu/Ir-catalyzed asymmetric allylic alkylation and intramolecular Friedel–Crafts reaction

Abstract

The development of enantioselective annulation reaction using readily available substrates for the construction of structurally and stereochemically diverse heterocycles is a compelling topic in diversity-oriented synthesis. Herein, we report an...

Recent Advances in the Catalytic Asymmetric Friedel–Crafts Reactions of Indoles

“…In another recent study, Wang et al disclosed an elegant synthetic strategy for the highly enantioselective synthesis of azepino­[3,4,5- cd ]­indole derivatives 161 , which are important structural frameworks frequently found in pharmaceuticals and bioactive compounds . The synthetic method was based on the cooperative Cu/Ir catalysis-catalyzed asymmetric 1,3-dipolar (3 + 4) cycloaddition between azomethine ylides and ambiphilic π-allyl iridium species, which were generated in situ from aldimine esters 160 and 4-indolyl allylic carbonates 159 , respectively.…”

“…In another recent study, Wang et al disclosed an elegant synthetic strategy for the highly enantioselective synthesis of azepino[3,4,5- cd ]indole derivatives 161 , which are important structural frameworks frequently found in pharmaceuticals and bioactive compounds. 70 The synthetic method was based on the cooperative Cu/Ir catalysis-catalyzed asymmetric 1,3-dipolar (3 + 4) cycloaddition between azomethine ylides and ambiphilic π-allyl iridium species, which were generated in situ from aldimine esters 160 and 4-indolyl allylic carbonates 159 , respectively. For improved stereochemical outcomes, the deployment of chiral Phosferrox ligand L47 and chiral phosphoramidite ligand L48 in generating a combined Cu(I)/( S , S p )- L47 /Ir(I)/( S a , S , S )- L48 dual catalyst system was proven to be an optimum catalytic system to realize the desired transformation.…”

Microwave-assisted rapid synthesis of chiral oxazolines

“…[25][26][27] Ferrocene PHOX is used in stereodivergent synthesis of enantioenriched azepino [3,4,5-cd]-indoles. 28 NarOX is a new ligand for C 2 -symmetric bis-nickel catalysts for enantioselective [4 + 1]-cycloaddition. 29 Besides the chiral oxazoline ligands mentioned in Fig.…”

Rhodium-Catalyzed Asymmetric (3 + 2 + 2) Annulation via N–H/C–H Dual Activation and Internal Alkyne Insertion toward N-Fused 5/7 Bicycles

“…However, the direct synthesis of bioactive 1-azabicyclo[5.3.0]­decane scaffolds from simple starting materials remains a great challenge due to the unfavorable entropy effects and transannular interactions to generate the medium-sized 7-membered ring. , Furthermore, the enantioselective construction of the inherent stereogenic center in the skeletons witnessed another nodus, particularly when introducing a hindered bridgehead quaternary stereocenter into the motif. The synthetic barrier to access such chiral skeletons will be remarkably magnified owing to their congested nature. − , Notably, chiral 1-azabicyclo[5.3.0]­decane scaffolds bearing a bridgehead quaternary stereocenter even demonstrate more important bioactivity. , As exemplified in Scheme (top), stemonamide, cephalotaxine, and tetrapetalones A–D have displayed demonstrable antitussive and insecticide activities, antileukemic activity, and inhibition of soybean lipoxygenase, respectively. The traditional routes to access such enantioenriched compounds need multiple steps with chiral starting materials.…”