Enantioselective Synthesis of Benzimidazole Atropisomers Featuring a N‐N Axis† DOI

Fang‐Bei Ge,

Qikun Yin,

Chuan‐Jun Lu

et al.

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 42(7), P. 711 - 718

Published: Dec. 8, 2023

Comprehensive Summary Atroposelective synthesis of N‐N atropisomers is an emerging area but remains underexplored; in particular, the benzimidazole still unprecedented. Herein, first enantioselective via palladium‐catalyzed de novo construction skeleton presented. With readily available palladium catalyst and biphosphine ligand, a broad range nonbiaryl indole‐benzimidazole were conveniently accessed high yields with excellent enantioselectivities. Significantly, these showed great antitumor activity selectivity to breast cancer MCF‐7 cells. The simple catalytic system, substrate scope, enantioselectivity, good bioactivity make this approach highly attractive.

Language: Английский

Catalytic Asymmetric Synthesis of Atropisomers Featuring an Aza Axis DOI
Jia Feng, Chuan‐Jun Lu, Renrong Liu

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(18), P. 2537 - 2554

Published: Sept. 11, 2023

ConspectusAtropisomers bearing a rotation-restricted axis are common structural units in natural products, chiral ligands, and drugs; thus, the prevalence of asymmetric synthesis has increased recent decades. Research into atropisomers featuring an N-containing (N-X atropisomers) remains its infancy compared with well-developed C-C atropisomer analogue. Notably, N-X could offer divergent scaffolds, which extremely important bioactive molecules. The is recognized as both appealing challenging. Recently, we devoted our efforts to catalytic atropisomers, benzimidazole-aryl N-C indole-aryl hydrogen-bond-assisted pyrrole-pyrrole N-N pyrrole-indole indole-indole atropisomers. To obtain Buchwald-Hartwig reaction amidines or enamines was employed. Using Pd(OAc)2/(S)-BINAP Pd(OAc)2/(S)-Xyl-BINAP catalyst system, were readily obtained. address issue reduced stability diarylamine axis, six-membered intramolecular N-H-O hydrogen bond introduced scaffold. A tandem N-arylation/oxidation process used for phosphoric acid (CPA)-catalyzed N-aryl quinone For copper-mediated Friedel-Crafts alkylation/arylation developed. desymmetrization completed successfully via Cu(OTf)2/chiral bisoxazoline (CuOTf)·Tol/bis(phosphine) dioxide thereby achieving first N/N bipyrrole Asymmetric amination utilized provide bisindole excellent stereogenic control. This scaffold using de novo indole construction strategy. heterobiaryl substantially facilitated palladium-catalyzed transient directing group (TDG)-mediated C-H functionalization. Atropisomeric alkenylation, allylation, alkynylation accomplished Pd(OAc)2/l-tert-leucine system. Herein, summarize work on palladium-, copper-, CPA-catalyzed syntheses Furthermore, application molecule analogues axially ligands demonstrated. Subsequently, briefly discussed terms single crystals obtained rotational barriers. Finally, outlook provided.

Language: Английский

Citations

59
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

58
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

53
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
Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles DOI Creative Commons
Shaojie Wang, Xia Wang,

Xiaolan Xin

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 15, 2024

Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and ligands. One efficient method the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis atropisomers with simultaneous creation contiguous axial central chirality by oxidative NHC ( N -heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able synthesize structurally diverse pyrroles indoles vicinal or bearing 2,3-dihydropyrimidin-4-one moiety moderate good yields excellent enantioselectivities. Further synthetic transformations obtained derivative products demonstrated. reaction mechanism origin enantioselectivity understood through DFT calculations.

Language: Английский

Citations

31
Catalytic atroposelective synthesis of indolyl quinazolinones bearing N–N/C–C diaxes DOI

Ning‐Yi Wang,

Shuo Gao,

Zhiwei Shu

et al.

Science China Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

Citations

5
N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of N–N Axially Chiral 3-Amino Quinazolinones DOI
Kuruva Balanna,

Soumen Barik,

Shilpa Barik

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(13), P. 8752 - 8759

Published: June 16, 2023

Although the atroposelective synthesis of biaryls and related compounds bearing axially chiral C–C bonds is well-known, C–N bond-containing relatively less explored, construction N–N has received only scant attention. Demonstrated herein N-heterocyclic carbene (NHC)-catalyzed selective amidation reaction, leading to 3-amino quinazolinones. The NHC-catalyzed reaction quinazolinones containing a free N–H moiety with α,β-unsaturated aldehydes under oxidative conditions furnished atropisomeric quinazolinone derivatives mild broad scope. Preliminary studies on experimental density functional theory-based rotational barrier determination are also presented.

Language: Английский

Citations

33
Recent advances in the construction of axially chiral arylpyrroles DOI

Yang‐Bo Chen,

Ye-Nan Yang,

Xuan-Zhu Huo

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(9), P. 2480 - 2491

Published: Aug. 9, 2023

Language: Английский

Citations

33
Design and Catalytic Asymmetric Synthesis of Furan‐Indole Compounds Bearing both Axial and Central Chirality DOI
Jing‐Yi Wang,

Cong‐Hui Gao,

Cheng Ma

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(8)

Published: Dec. 29, 2023

Abstract In the chemistry community, catalytic asymmetric synthesis of furan‐based compounds bearing both axial and central chirality has proven to be a significant but challenging issue owing importance difficulty in constructing such frameworks. this work, we have realized first five‐five‐membered via organocatalytic (2+4) annulation achiral furan‐indoles with 2,3‐indolyldimethanols uncommon regioselectivity. By strategy, furan‐indole were synthesized high yields excellent regio‐, diastereo‐, enantioselectivities. Moreover, theoretical calculations conducted provide an in‐depth understanding reaction pathway, activation mode, origin selectivity.

Language: Английский

Citations

33
Synthesis of Axially Chiral Biaryls through Cobalt(II)‐Catalyzed Atroposelective C−H Arylation DOI

Yong‐Jie Wu,

Zhen‐Kai Wang,

Zhen‐Sheng Jia

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 16, 2023

Highly efficient synthesis of axially chiral biaryl amines through cobalt-catalyzed atroposelective C-H arylation using easily accessible cobalt(II) salt and salicyloxazoline ligand has been reported. This methodology provides a straightforward sustainable access to broad range enantioenriched biaryl-2-amines in good yields (up 99 %) with excellent enantioselectivities % ee). The synthetic utility the unprecedented method is highlighted by its scalability diverse transformations.

Language: Английский

Citations

31