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

Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field DOI
Hong‐Hao Zhang,

Tian‐Zhen Li,

Si‐Jia Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(3)

Published: Nov. 2, 2023

With the rapid development of asymmetric catalysis, demand for enantioselective synthesis complex and diverse molecules with different chiral elements is increasing. Owing to unique features atropisomerism, catalytic atropisomers has attracted a considerable interest from chemical science community. In particular, introducing additional elements, such as carbon centered chirality, heteroatomic planar helical into provides an opportunity incorporate new properties axially compounds, thus expanding potential applications atropisomers. Thus, it important perform transformations synthesize bearing multiple elements. spite challenges in transformations, recent years, chemists have devised powerful strategies under organocatalysis or metal synthesizing wide range enantioenriched Therefore, become emerging field. This review summarizes progress this field indicates challenges, thereby promoting horizon.

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

56
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

55
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
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

29
Organocatalytic Enantioselective Synthesis of Seven‐Membered Ring with Inherent Chirality DOI
Jia‐Hao Li, Xiaokai Li, Jia Feng

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(8)

Published: Jan. 8, 2024

Abstract Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical and has tremendous applications in recognition enantioselective synthesis. Catalytic divergent syntheses inherently have attracted increasing interest from chemists. Herein, we report the synthesis tribenzocycloheptene derivatives via phosphoric acid (CPA)‐catalyzed condensation ketones hydroxylamines. This chemistry paves way accessing less stable 7‐membered rings with inherent chirality. A series oxime ethers was synthesized good yields (up 97 %) excellent enantioselectivities 99 % ee).

Language: Английский

Citations

25
Catalytic asymmetric (3 + 3) cycloaddition between different 2-indolylmethanols DOI
Tianzhen Li, Sijia Liu, Shufang Wu

et al.

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 2629 - 2636

Published: June 26, 2024

Language: Английский

Citations

24
Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality DOI Creative Commons
Shuang Yang,

Jia-Bo Huang,

Dahua Wang

et al.

Precision Chemistry, Journal Year: 2024, Volume and Issue: 2(5), P. 208 - 220

Published: April 23, 2024

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via phosphoric acid-catalyzed addition reactions C3-unsubstituted with

Language: Английский

Citations

16
Advances in organocatalytic asymmetric [3 + 3] cycloadditions: synthesis of chiral six-membered (hetero)cyclic compounds DOI

Ziqi Zhu,

Tian‐Zhen Li,

Sijia Liu

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(19), P. 5573 - 5604

Published: Jan. 1, 2024

This review has summarized the development of organocatalytic asymmetric [3 + 3] cycloadditions and given insights into remaining challenges to promote future this field.

Language: Английский

Citations

16