Axially Chiral Aryl‐Alkene‐Indole Framework: A Nascent Member of the Atropisomeric Family and Its Catalytic Asymmetric Construction

Abstract

of main observation and conclusion A new class of axially chiral aryl-alkene-indole frameworks have been designed, and the first catalytic asymmetric construction of such scaffolds has been established by the strategy of organocatalytic (Z/E)-selective and enantioselective (4+3) cyclization of 3-alkynyl-2-indolylmethanols with 2-naphthols or phenols (all >95 : 5 E/Z, up to 98% yield, 97% ee). This reaction also represents the first catalytic asymmetric construction of axially chiral alkene-heteroaryl scaffolds, which will add a new member to the atropisomeric family. This approach has not only confronted the great challenges in constructing axially chiral alkene-heteroaryl scaffolds but also provided a powerful strategy for the enantioselective construction of axially chiral aryl-alkene-indole frameworks.

Regio‐ and Enantioselective (3+3) Cycloaddition of Nitrones with 2‐Indolylmethanols Enabled by Cooperative Organocatalysis

“…First, we investigated the substrate scope of nitrones 2 ( Table 2). As shown in entries 1-12, avariety of nitrones 2a-2l bearing different Rs ubstituents,s uch as para-, meta-, or ortho-substituted phenyl groups ( Table 2, entries 1-11) and a2-naphthyl group (Table 2, entry 12), smoothly participated in the reaction to give products 3aa-3al in overall high yields with excellent enantioselectivities.More importantly,nitrones 2m-2n bearing heteroaromatic (2-furyl) and aliphatic (ethyl) Rg roups successfully underwent enantioselective (3+ +3) cycloaddition with 2-indolylmethanol 1a in moderate to good yields with high enantioselectivities ( Table 2, entries [13][14]. In addition, the R 1 group of the nitrones could be changed from am ethyl to ap henyl group (Table 2, entry 15), and although this substrate 2o exhibited much lower reactivity,it ultimately participated in the reaction to afford product 3ao with good enantioselectivity.I ts hould be noted that in all cases,regioisomers 3' ' were not observed.…”

“…In this context, we wondered whether 2-indolylmethanols could serve as suitable three-atom reaction partners to undergo organocatalytic asymmetric (3+ +3) cycloaddition with nitrones.T his consideration is based on our understanding of the chemistry of 2-indolylmethanols (Scheme 2). [11][12][13] In recent years,2 -indolylmethanols have proven to be versatile reactants in organocatalytic asymmetric reactions due to their unique property of C3 electrophilicity, [11] and they have been widely used in catalytic asymmetric C3-electrophilic substitutions [14] and cycloadditions [15] (Scheme 2a). However,i ns harp contrast, the C3 nucleophilicity of 2indolylmethanols has scarcely been reported, and the catalytic asymmetric C3-nucleophilic reactions of 2-indolylmethanols are rather underdeveloped (Scheme 2b).…”

Chiral Phosphoric Acid: A Powerful Organocatalyst for the Asymmetric Synthesis of Heterocycles with Chiral Atropisomerism

“…Shi, Jiao and co‐workers recently documented a new class of atropisomeric aryl‐alkene‐indole skeletons featuring a seven‐membered ring and established an enantioselective and ( Z / E )‐selective [4+3] cyclization reaction between 3‐alkynyl‐2‐indolylmethanols 134 and 2‐naphthols 37 or phenols 39 to construct such scaffolds [40] . The screening of catalysts revealed H 8 ‐BINOL‐derived CPA21 was optimal, which promoted the designed reactions with high reactivity and enantioselectivity (all >95 : 5 E / Z , 41–98 % yields, 89–97 % ee ).…”

Mg‐catalyzed one‐pot preparation of benzimidazoles and spirooxindoles by an immobilized chlorophyll b on magnetic nanoparticles

“…Their pharmaceutical and biological relevance have persuaded researchers to develop new efficient, selective, environmentally friendly, and economical methodologies to synthesize these compounds. [ 4,5 ] Indole frameworks are present in a broad range of natural and synthetic drugs, and indole‐fused heterocycles have attracted the attention of pharmacologists and chemists due to their wide range of bioactivities, such as topoisomerase I inhibitors TAS‐103 and NSC 314622. [ 6,7 ] Spirooxindole compounds are one of the types of N ‐containing heterocyclic compounds, and MCRs containing nitrogen atoms found in most natural alkaloids and their various biological and pharmacological activities such as antimicrobial, [ 8 ] antiviral, anticancer, [ 9 ] antioxidant, anti‐HIV, and neuroprotective agents [ 10 ] are known.…”