Design and synthesis of axially chiral aryl-pyrroloindoles via the strategy of organocatalytic asymmetric (2 + 3) cyclization

Wu, Ping; Lei, Yu; Gao, Cong‐Hui; Cheng, Qi; Deng, Shuang; Jiao, Yinchun; Tan, Wei; Shi, Feng

doi:10.1016/j.fmre.2022.01.002

Cited by 52 publications

(23 citation statements)

References 52 publications

(74 reference statements)

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“…On the basis of this strategy, we designed the organocatalytic enantioselective (2 + 3) cycloaddition of 3-arylindoles 34 with propargylic alcohols 45 as 1,3dielectrophiles under the catalysis of CPA (S)-C3 to afford arylpyrroloindoles 46 in good yields with high atroposelectivities (Scheme 14b). 42 Moreover, this protocol could be applied to propargylic alcohol 47 bearing different R 2 and R 3 substituents, which would afford aryl-pyrroloindoles 48 bearing multiple chiral elements in excellent diastereo-and atroposelectivities. Therefore, this approach not only provides aryl-pyrroloindoles as a new class of atropisomeric compounds but also offers a useful strategy for constructing 3-arylindole-related atropisomeric skeletons.…”

Section: -Arylindoles As Platform Moleculesmentioning

confidence: 99%

“…Notably, this strategy has some advantages, such as generating a new ring and a novel type of atropisomeric skeleton with multiple chiral elements. On the basis of this strategy, we designed the organocatalytic enantioselective (2 + 3) cycloaddition of 3-arylindoles 34 with propargylic alcohols 45 as 1,3-dielectrophiles under the catalysis of CPA ( S )-C3 to afford aryl-pyrroloindoles 46 in good yields with high atroposelectivities (Scheme b) . Moreover, this protocol could be applied to propargylic alcohol 47 bearing different R 2 and R 3 substituents, which would afford aryl-pyrroloindoles 48 bearing multiple chiral elements in excellent diastereo- and atroposelectivities.…”

Section: (Hetero)arylindoles As Platform Molecules To Synthesize Axia...mentioning

confidence: 99%

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

2022

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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...

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Section: -Arylindoles As Platform Moleculesmentioning

confidence: 99%

Section: (Hetero)arylindoles As Platform Molecules To Synthesize Axia...mentioning

confidence: 99%

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

2022

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“…13 Independently, Shi and coworkers realized the asymmetric synthesis of aryl-pyrroloindoles with axial and central chirality via an organocatalytic asymmetric (2 + 3) cyclization of 3-arylindoles with propargylic alcohols (Scheme 1A). 14 They also found that the auxiliary group of propargylic alcohols played a key role in controlling the enantioselectivity. Based on our previous work on the reactions of functionalized propargylic alcohols, 11 b ,12 a ,13 c – f we have successfully developed diverse organocatalytic reactions of α-(3-isoindolinonyl) propargylic alcohols, 15 a,b which in situ generated β,γ-alkynyl-α-imines under acidic conditions.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric organocatalytic (3 + 2) annulation of propargylic alcohols with indolylnaphthalenols: synergistic construction of axial and central chirality

et al. 2023

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“…1 This chiral subunit widely exists in numerous bioactive molecules, natural products, chiral catalysts or ligands, and other functional molecules. 2 Thus, synthesizing axially chiral molecules has attracted extensive attention among researchers. 3 Recent literature has mainly documented research involving the atroposelective synthesis of chiral compounds bearing the C–C or C–N chiral axis (Scheme 1a).…”

mentioning

confidence: 99%

Chiral phosphoric acid-catalyzed dual-ring formation for enantioselective construction of N–N axially chiral 3,3′-bisquinazolinones

Zhang

Liu

et al. 2022

Chem. Commun.

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Design and synthesis of axially chiral aryl-pyrroloindoles via the strategy of organocatalytic asymmetric (2 + 3) cyclization

Cited by 52 publications

References 52 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

Asymmetric organocatalytic (3 + 2) annulation of propargylic alcohols with indolylnaphthalenols: synergistic construction of axial and central chirality

Chiral phosphoric acid-catalyzed dual-ring formation for enantioselective construction of N–N axially chiral 3,3′-bisquinazolinones

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