Catalytic Asymmetric Synthesis of Axially Chiral 3,3'‐Bisindoles by Direct Coupling of Indole Rings

Sheng, Feng‐Tao; Yang, Shuang; Wu, Shufang; Zhang, Yu‐Chen; Shi, Feng

doi:10.1002/cjoc.202200327

Cited by 97 publications

(30 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…According to this strategy and making avail of the C3-umpolung reactivity of 2-indolylmethanols, our group devised a nucleophilic addition of 2-indolylmethanols with well-designed C2-substituted indoles under the promotion of B*−H toward the atroposelective synthesis of 3,3′-bisindoles (Scheme 3c). 33 Notably, our designed 2-substituted indoles bearing an orthoamide-substituted benzyl group are based on the consideration that the benzyl group serves as a bulky group and that the amide group acts as both an activation and postfunctionalization group (Scheme 3d).…”

Section: -Indolylmethanols As Platform Moleculesmentioning

confidence: 99%

“…We investigated the potential of atropisomeric 3,3′-bisindoles in developing new catalysts by performing postfunctionalizations of 3,3′-bisindole 11a by making use of the amino group of compound 12, which afforded a series of 3,3′-bisindole-derived organocatalyst-like compounds 13−16 (Scheme 5a). 33 More importantly, we carried out preliminary application of these organocatalysts in enantioselective reactions. As illustrated in Scheme 5b, 3,3′-bisindole-derived organocatalyst 15c could efficiently catalyze the enantioselective Morita−Baylis−Hillman reaction to give product 19 in good yield with high enantioselectivity.…”

Section: -Indolylmethanols As Platform Moleculesmentioning

confidence: 99%

“…Namely, if two indole derivatives bearing a bulky C2-substitutent display distinct C3-reactivities, they are able to undergo formal cross-coupling under the chiral organocatalytic activation and, therefore, synthesize atropisomeric 3,3′-bisindoles because of the steric congestion between the two ortho -bulky substituents. According to this strategy and making avail of the C3-umpolung reactivity of 2-indolylmethanols, our group devised a nucleophilic addition of 2-indolylmethanols with well-designed C2-substituted indoles under the promotion of B*–H toward the atroposelective synthesis of 3,3′-bisindoles (Scheme c) …”

Section: Indolylmethanols As Platform Molecules To Synthesize Axially...mentioning

confidence: 99%

“…Using this strategy, we accomplished the enantioselective addition of rationally designed 2-substituted indoles 10 with 2-indolylmethanols 1 by using sulfur-substituted CPA ( S )-C2 as a chiral organocatalyst, which resulted in the synthesis of atropisomeric 3,3′-bisindoles 11 in considerable yields with high atroposelectivities (Scheme a) . Notably, the barrier of product 11a for rotation was calculated as 119.66 kJ mol –1 , which is much lower than that of 3-naphthylindole 3a (Scheme ), therefore demonstrating that atroposelective construction of five–five-membered heterobiaryls is indeed far more challenging than that of five–six-membered heterobiaryls.…”

Section: Indolylmethanols As Platform Molecules To Synthesize Axially...mentioning

confidence: 99%

Section: Indolylmethanols As Platform Molecules To Synthesize Axially...mentioning

confidence: 99%

See 4 more Smart Citations

Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications

2022

Self Cite

View full text Add to dashboard Cite

Conspectus Catalytic atroposelective syntheses of axially chiral compounds have stimulated extensive interest in multiple communities, such as synthetic chemistry, biochemistry, and materials science, because of the intriguing characteristics of atropisomerism. In particular, atropisomeric indole derivatives, which contain a kind of five-membered heterocyclic framework, are widely distributed in a number of natural alkaloids, biologically relevant compounds, chiral ligands, and chiral organocatalysts. Hence, the catalytic atroposelective synthesis of indole derivatives bearing axial chirality is of considerable importance and has become an emerging focus of research. However, there are substantial challenges associated with the atroposelective synthesis of indole derivatives, including remote ortho-substituents around the chiral axis, a lower barrier for rotation, and a weaker configurational stability than that of atropisomeric six-membered biaryls. Therefore, the development of effective strategies toward the catalytic atroposelective synthesis of indole derivatives has become an urgent task. In order to tackle these challenges and to accomplish the task, our group devised a unique strategy of designing indole-derived platform molecules and developing organocatalytic enantioselective transformations of such platform molecules to synthesize atropisomeric indole derivatives; asymmetric organocatalysis has tremendous advantages and was the research area recognized by the Nobel Prize in Chemistry in 2021. This Account summarizes our endeavors in the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality. In brief, we devised and developed a series of indole-derived platform molecules, such as indolylmethanols, (hetero)aryl indoles, oxindole-based styrenes, N-aminoindoles, and indole-based homophthalic anhydrides, by introducing different functional groups onto the indole ring to achieve new reactivity and modulate the reactive site of the indole ring. As a result, these indole-derived platform molecules possess versatile and unique reactivity and are capable of undergoing a variety of organocatalytic enantioselective transformations for preparing structurally diversified indole derivatives with axial chirality. We used these strategies to accomplish the atroposelective synthesis of plenty of indole derivatives with axial chirality, including (hetero)aryl indoles, alkene-indoles, oxindole-based styrenes, N-pyrrolylindoles, and isochromenone-indoles. In addition, we gave a thorough and detailed understanding of the designed reaction by investigating the reaction pathway and activation mode. More importantly, we studied the biological activity of some products and performed catalyst design on the basis of atropisomeric indole moieties, which are helpful for disclosing more applications of indole derivatives bearing axial chirality. In the future, the organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality will indubitably remain a frontier topic in the...

show abstract

Section: -Indolylmethanols As Platform Moleculesmentioning

confidence: 99%

Section: -Indolylmethanols As Platform Moleculesmentioning

confidence: 99%

Section: Indolylmethanols As Platform Molecules To Synthesize Axially...mentioning

confidence: 99%

Section: Indolylmethanols As Platform Molecules To Synthesize Axially...mentioning

confidence: 99%

Section: Indolylmethanols As Platform Molecules To Synthesize Axially...mentioning

confidence: 99%

See 3 more Smart Citations

Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications

2022

Self Cite

View full text Add to dashboard Cite

show abstract

Recent Progress of Electron‐Withdrawing‐Group‐Tethered Arenes Involved Asymmetric Nucleophilic Aromatic Functionalizations

Wang

2022

Adv Synth Catal

View full text Add to dashboard Cite

Electron-withdrawing groups (EWG) have emerged as a powerful tool for the activation of various arenes to promote nucleophilic dearomative additions for the construction of complicated chiral cyclic structures under asymmetric catalytic systems. Nitro-indoles, nitro-benzofurans/benzothiophenes, and related nitro-heteroarenes are widely applied in the reaction with various nucleophiles to construct various enantioenriched polycyclic skeletons via the asymmetric dearomatization process. Meanwhile, the electron-deficient azo-group and nitroso-group are an alternative powerful tool for the activation of arenes, which enable formal nucleophilic aromatic arylations with various electrophilic aromatics to construct novel chiral biaryl atropisomers. Besides, azo-naphthanenes are served as dipolar surrogates in the reaction with nucleophilic dipolarophiles to proceed asymmetric cycloadditions to construct chiral polycyclic skeletons. The EWG-tethered arene has proven to be a versatile protocol for the construction of structurally diversified chiral backbones. This review summarizes the latest progress of the EWG-tethered arenes involved asymmetric transformations under organo-or transition metal catalysis.1.

show abstract

N‐Heterocyclic Carbene Control over Multiple Stereogenicities: Atroposelective Synthesis of Axially Chiral Phthalimides

et al. 2023

View full text Add to dashboard Cite

The design of a NHC‐catalyzed methodology for the straightforward access to hitherto unknown axially chiral N‐aryl phthalimides has provided a breakthrough in the field of multichirality control. Anticipating a formal (4+2) oxidative annulation, the use of NHC‐derived chiral dienolate as ambident partner toward N‐aryl maleimides unexpectedly yields original bis‐succinimide‐type compounds featuring a multichiral architecture with up to four stereogenic centers and two remote chiral axes. The overall pseudo‐three components reaction between an enal and two equivalents of a N‐aryl maleimide proceeds with excellent enantioselectivity and complete diastereoselectivity. This study illustrates the high synthetic potential of chiral NHC‐activated dienolates for the rapid and highly diastereo‐ and enantioselective preparation of underexplored atropisomers in the pentatomic series, featuring multiple stereogenic elements including challenging Csp2−N chiral axes. The practicality of this reaction is highlighted by a broad substrate scope and a scaled‐up synthesis. Moreover, the easy base‐induced transformation of the chiral bis‐succinimide precursors allows to prepare the initially planned N‐aryl phthalimide atropisomers with excellent retention of enantiopurity.

show abstract

Catalytic Asymmetric Synthesis of Axially Chiral 3,3'‐Bisindoles by Direct Coupling of Indole Rings

Cited by 97 publications

References 115 publications

Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications

Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications

Recent Progress of Electron‐Withdrawing‐Group‐Tethered Arenes Involved Asymmetric Nucleophilic Aromatic Functionalizations

N‐Heterocyclic Carbene Control over Multiple Stereogenicities: Atroposelective Synthesis of Axially Chiral Phthalimides

Contact Info

Product

Resources

About