Organocatalytic atroposelective synthesis of axially chiral N,N′-pyrrolylindoles via de novo indole formation DOI Creative Commons

Cong-Shuai Wang,

Qi Xiong, Hui Xu

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(43), P. 12091 - 12097

Published: Jan. 1, 2023

The first organocatalytic atroposelective synthesis of axially chiral N,N'-pyrrolylindoles based on o-alkynylanilines was successfully established via de novo indole formation catalyzed by phosphoric acid (CPA). This new synthetic strategy introduced CPA-catalyzed asymmetric 5-endo-dig cyclization well-designed containing a pyrrolyl unit, resulting in wide range high yields with exclusive regioselectivity and excellent enantioselectivity (up to 99% yield, >20 : 1 rr, 95 5 er). Considering the potential biological significance N-N atropisomers, preliminary activity studies were performed revealed that these structurally important had low IC50 value promising impressive cytotoxicity against several kinds cancer cell lines. DFT reveal N-nucleophilic mediated CPA is rate- stereo-determining step, which ligand-substrate dispersion interactions facilitate axial chirality target products.

Language: Английский

Atropisomers beyond the C–C axial chirality: Advances in catalytic asymmetric synthesis DOI Creative Commons
Guang‐Jian Mei, Wai Lean Koay,

Chun-Yan Guan

et al.

Chem, Journal Year: 2022, Volume and Issue: 8(7), P. 1855 - 1893

Published: May 6, 2022

Language: Английский

Citations

255
Organocatalytic Atroposelective Synthesis of N−N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation DOI

Ke‐Wei Chen,

Zhi‐Han Chen,

Shuang Yang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(17)

Published: Jan. 26, 2022

Abstract The first highly atroposelective construction of N−N axially chiral indole scaffolds was established via a new strategy de novo ring formation. This makes use the organocatalytic asymmetric Paal–Knorr reaction well‐designed N ‐aminoindoles with 1,4‐diketones, thus affording ‐pyrrolylindoles in high yields and excellent atroposelectivities (up to 98 % yield, 96 ee). In addition, this is applicable for synthesis bispyrroles 97 More importantly, such heterocycles can be converted into organocatalysts applications catalysis, some molecules display potent anticancer activity. work not only provides but also offers members atropisomer family promising synthetic medicinal chemistry.

Language: Английский

Citations

138
Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles DOI

Zhi‐Han Chen,

Tian‐Zhen Li,

Ning‐Yi Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 7, 2023

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N'-bisindoles via phosphoric acid-catalyzed formal (3+2) cycloadditions indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various were synthesized in good yields and excellent enantioselectivities (up to 87 % yield 96 ee). More importantly, class exhibited some degree cytotoxicity toward cancer cells was derived into phosphine ligands high catalytic activity. provides a strategy for using asymmetric organocatalysis realize applications such scaffolds medicinal chemistry catalysis.

Language: Английский

Citations

90
Atroposelective Synthesis of 1,1′‐Bipyrroles Bearing a Chiral N−N Axis: Chiral Phosphoric Acid Catalysis with Lewis Acid Induced Enantiodivergence DOI
Yaru Gao,

Luo‐Yu Wang,

Tao Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(16)

Published: Feb. 17, 2022

Abstract We present herein a highly efficient atroposelective synthesis of axially chiral 1,1′‐bipyrroles bearing an N−N linkage from simple hydrazine and 1,4‐diones. Further product derivatizations led to bifunctional compounds with high potential in asymmetric catalysis. For this chrial phosphoric acid (CPA)‐catalyzed double Paal–Knorr reaction, intriguing Fe(OTf) 3 ‐induced enantiodivergence was also observed.

Language: Английский

Citations

81
Enantioselective Synthesis of N−N Bisindole Atropisomers DOI
Peng Zhang, Qi Xu, Xiaomei Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(44)

Published: Sept. 15, 2022

N-N Atropisomers are a common motif in natural products and represent significant dimension for exploration modern pharmaceutical medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective bisindole atropisomers is unprecedented. Herein, first via palladium-catalyzed de novo construction one indole skeleton presented. A wide variety axially chiral bisindoles were generated good yields with excellent enantioselectivities cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indole-carbazole, non-biaryl-indole possessing axis accessed using this protocol. Moreover, investigations density functional theory (DFT) calculations provided insight into reaction mechanism enantiocontrol.

Language: Английский

Citations

76
Enantioselective Synthesis of N−N Biaryl Atropisomers through Iridium(I)‐Catalyzed C−H Alkylation with Acrylates DOI Open Access

Si‐Yong Yin,

Qiansujia Zhou,

Chen‐Xu Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(37)

Published: May 4, 2023

Abstract Enantioselective synthesis of N−N biaryl atropisomers is an emerging area but remains underexplored. The development efficient in great demand. Herein, the construction through iridium‐catalyzed asymmetric C−H alkylation reported for first time. In presence readily available Ir precursor and Xyl‐BINAP, a variety axially chiral molecules based on indole‐pyrrole skeleton were obtained good yields (up to 98 %) with excellent enantioselectivity 99 % ee). addition, bispyrrole could also be synthesized enantioselectivity. This method features perfect atom economy, wide substrate scope, multifunctionalized products allowing diverse transformations.

Language: Английский

Citations

57
Enantioselective Synthesis of N‐N Atropisomers by Palladium‐Catalyzed C−H Functionalization of Pyrroles DOI
Yao Wang, Chuan‐Jun Lu,

Li‐Wen Zhan

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: March 21, 2023

The catalytic asymmetric construction of N-N atropisomeric biaryls remains a formidable challenge. Studies them lag far behind studies the more classical carbon-carbon biaryl atropisomers, hampering meaningful development. Herein, first palladium-catalyzed enantioselective C-H activation pyrroles for synthesis atropisomers is presented. Structurally diverse indole-pyrrole possessing chiral axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, kinetic resolution trisubstituted heterobiaryls sterically demanding substituents was also achieved. Importantly, this versatile functionalization strategy enables iterative exquisite selectivity, expediting formation valuable, complex, atropisomers.

Language: Английский

Citations

54
Cobalt-catalyzed atroposelective C−H activation/annulation to access N−N axially chiral frameworks DOI Creative Commons
Tong Li, Linlin Shi,

Xinhai Wang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 29, 2023

The N-N atropisomer, as an important and intriguing chiral system, was widely present in natural products, pharmaceutical lead compounds, advanced material skeletons. anisotropic structural characteristics caused by its special axial rotation have always been one of the challenges that chemists strive to overcome. Herein, we report efficient method for enantioselective synthesis axially frameworks via a cobalt-catalyzed atroposelective C-H activation/annulation process. reaction proceeds under mild conditions using Co(OAc)2·4H2O catalyst with salicyl-oxazoline (Salox) ligand O2 oxidant, affording variety products high yields enantioselectivities. This protocol provides approach facile construction atropisomers further expands range derivatives. Additionally, electrocatalysis, desired were also successfully achieved good excellent efficiencies

Language: Английский

Citations

52
Catalytic Asymmetric Synthesis of Axially Chiral Diaryl Ethers through Enantioselective Desymmetrization DOI

Hanyang Bao,

Yunrong Chen, Xiaoyu Yang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(14)

Published: Feb. 10, 2023

Axially chiral diaryl ethers are a type of unique atropisomers bearing two potential axes, which have applications in variety research fields. However, the catalytic enantioselective synthesis these ether is largely underexplored when compared to asymmetric biaryl or other types atropisomers. Herein, we report highly efficient through an organocatalyzed desymmetrization protocol. The phosphoric acid-catalyzed electrophilic aromatic aminations symmetrical 1,3-benzenediamine substrates afforded series excellent yields and enantioselectivities. facile construction heterocycles by utilizations 1,2-benzenediamine moiety products provided access structurally diverse novel azaarene-containing

Language: Английский

Citations

50
Enantioselective Strategies for The Synthesis of N−N Atropisomers DOI Creative Commons
Giovanni Centonze, Chiara Portolani, Paolo Righi

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(31)

Published: April 25, 2023

Axially chiral compounds have been always considered a laboratory curiosity with rare prospects of being applied in asymmetric synthesis. Things changed very quickly the last twenty years when it was understood important role and enormous impact that these medicinal, biological material chemistry. The synthesis atropisomers became rapidly expanding field recent reports on development N-N strongly prove how this research is hot topic open to new challenges frontiers This review focuses advances enantioselective highlighting strategies breakthroughs obtain novel stimulating atropisomeric framework.

Language: Английский

Citations

49