Atroposelective Synthesis of N–N Axially Chiral Indoles and Pyrroles via NHC-Catalyzed Diastereoselective (3 + 3) Annulation Strategy DOI

Sowmya Shree Ranganathappa,

Bhabani Sankar Dehury,

Gautam Kumar Singh

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 6965 - 6972

Published: April 18, 2024

The synthesis of N–N axially chiral molecules in the enantiopure form has emerged as an interesting research topic primarily due to significance and intricacy synthesizing these molecules, especially bearing heterocyclic motifs. Herein, we disclose a method for introduction axial chirality along with point center via N-heterocyclic carbene (NHC)-catalyzed atroposelective dihydropyridinone-containing indoles pyrroles. reaction follows (3 + 3) annulation approach by interception indole/pyrrole-derived enamines α,β-unsaturated aldehydes under oxidative NHC catalysis proceeding acylazoliums. indoles/pyrroles were formed mild conditions broad scope high selectivity. In addition, preliminary DFT studies rotational barrier products performed.

Language: Английский

Recent Progress toward the Construction of Axially Chiral Molecules Catalyzed by an N-heterocyclic Carbene DOI

Jiaming Wang,

Changgui Zhao, Jian Wang

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(20), P. 12520 - 12531

Published: Sept. 28, 2021

Axial chirality widely exists in natural products, pharmaceutical compounds, and other functional molecules; these axially chiral compounds also find wide utility as catalysts or ligands organic synthetic chemistry. Nevertheless, whereas significant progress has been made toward the synthesis of enantioenriched molecules over past two decades, strategies involving organocatalysis have only started to emerge recently. N-heterocyclic carbene (NHC) organocatalysts recognized be powerful tools for rapid construction complex molecular architectures. However, previous works mainly focused on assembly point recently it realized that asymmetric axial could achieved by using NHCs organocatalysts. This Perspective highlights developments advances scaffolds catalyzed NHCs. The aim this is provide an overview area serve a stepping stone future investigations.

Language: Английский

Citations

127
Transition Metal-Catalyzed Biaryl Atropisomer Synthesis via a Torsional Strain Promoted Ring-Opening Reaction DOI
Xue Zhang, Kun Zhao, Zhenhua Gu

et al.

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(12), P. 1620 - 1633

Published: June 1, 2022

ConspectusArising from the restricted rotation of a single bond caused by steric or electronic effects, atropisomerism is one few fundamental categories for molecules to manifest their three-dimensional characters into which axially chiral biaryl compounds fall. Despite widespread occurrence skeletons in natural products, bioactive molecules, and ligands/organocatalysts, catalytic asymmetric methods synthesis these structures still lag behind demand. Major challenges preparation biaryls include accessing highly sterically hindered variants while controlling stereoselectivity. A couple useful strategies have emerged direct last two decades.Recently, we engaged atropisomers via transition metal catalysis, including ring-openings dibenzo cyclic compounds. During studies, serendipitously discovered that substituents adjacent axis cause be distorted minimize repulsion. The display higher reactivity ring-opening reactions than non-distorted molecules. In other words, torsional strain can promote reaction. On basis this concept, successfully realized reaction diaryliodoniums, silanes, 9H-fluoren-9-ols, delivered several differently substituted ortho tetra-substituted high enantioselectivity. not only activates substrates toward under mild conditions but also changes chemoselectivity bond-breaking events. palladium-catalyzed carboxylation S-aryl dibenzothiophenium, inversed selectivity exocyclic C–S cleavage reaction.In Account, summarize our studies on copper-, rhodium-, as collection straightforward with enantiopurity above-mentioned strain-promoted coupling strategy. part, energies are discussed aid density functional theory (DFT) calculations.

Language: Английский

Citations

125
Progress in organocatalytic asymmetric (4+3) cycloadditions for the enantioselective construction of seven-membered rings DOI
Wei Tan, Jiayi Zhang,

Cong‐Hui Gao

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(4), P. 966 - 992

Published: Feb. 15, 2023

Language: Английский

Citations

81
Recent Progress in Cyclic Aryliodonium Chemistry: Syntheses and Applications DOI Creative Commons
Xiaopeng Peng, Abdur Rahim, Weijie Peng

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(4), P. 1364 - 1416

Published: Jan. 17, 2023

Hypervalent aryliodoumiums are intensively investigated as arylating agents. They excellent surrogates to aryl halides, and moreover they exhibit better reactivity, which allows the corresponding arylation reactions be performed under mild conditions. In past decades, acyclic aryliodoniums widely explored However, unmet need for is improvement of their notoriously low reaction economy because coproduced iodides during often wasted. Cyclic have intrinsic advantage in terms economy, started receive considerable attention due valuable synthetic applications initiate cascade reactions, can enable construction complex structures, including polycycles with potential pharmaceutical functional properties. Here, we summarizing recent advances made research field cyclic aryliodoniums, nascent design aryliodonium species applications. First, general preparation typical diphenyl iodoniums described, followed by heterocyclic monoaryl iodoniums. Then, initiated arylations coupled subsequent domino summarized construct polycycles. Meanwhile, building biaryls axial atropisomers discussed a systematic manner. Finally, very advance employed halogen-bonding organocatalysts described.

Language: Английский

Citations

71
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
Enantioselective Access to Triaryl-2-pyrones with Monoaxial or Contiguous C–C Diaxes via Oxidative NHC Catalysis DOI

Si-Chen Zhang,

Shengping Liu, Xia Wang

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(4), P. 2565 - 2575

Published: Feb. 6, 2023

We present herein an unprecedented stereoselective synthesis of triaryl-2-pyrones with monoaxial or contiguous diaxes from readily available starting materials. This N-heterocyclic carbene catalysis method adopts atroposelective annulation 2-aryketones ynals under oxidative conditions. The includes the construction one two axes in a single operation, achieves step economy, and affords axially chiral moderate to good yields, high excellent enantioselectivities. DFT calculations relative energies stereoisomers rotational barriers were performed.

Language: Английский

Citations

43
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
Amide C–N bonds activation by A new variant of bifunctional N-heterocyclic carbene DOI Creative Commons

Yuxing Cai,

Yuxin Zhao,

Kai Tang

et al.

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

Published: Jan. 12, 2024

Abstract We report an organocatalyst that combines a triazolium N-heterocyclic carbene (NHC) with squaramide as hydrogen-bonding donor (HBD), which can effectively catalyze the atroposelective ring-opening of biaryl lactams via unique amide C–N bond cleavage mode. The free species attacks carbonyl, forming axially chiral acyl-azolium intermediate. Various amines be accessed by this methodology up to 99% ee and yield. By using mercaptan catalyst turnover agent, resulting thioester synthon transformed into several interesting atropisomers. Both control experiments theoretical calculations reveal crucial role hybrid NHC-HBD skeleton, activates H-bonding brings it spatially close centre. This discovery illustrates potential chimera demonstrates complementary strategy for activation manipulation.

Language: Английский

Citations

17
Synthesis of Axially Chiral Aldehydes by N‐Heterocyclic‐Carbene‐Catalyzed Desymmetrization Followed by Kinetic Resolution DOI

Yingtao Wu,

Mingrui Li, Jiaqiong Sun

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(14)

Published: Jan. 31, 2022

Axially chiral aldehydes have received increasing attention in enantioselective catalysis. However, only very few catalytic methods been developed to construct structurally diverse axially aldehydes. We herein describe an NHC-catalyzed atroposelective esterification of biaryl dialdehydes as a general and practical strategy for the construction Mechanistic studies indicate that coupling proceeds through novel combination desymmetrization kinetic resolution. This protocol features excellent enantioselectivity, mild conditions, good functional-group tolerance, applicability late-stage functionalization provides modular platform synthesis their derivatives.

Language: Английский

Citations

69