Enantioselective Synthesis of Axially Chiral Diaryl Ethers via NHC Catalyzed Desymmetrization and Following Resolution

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(4)

Published: Nov. 29, 2023

Axially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access ether atropisomers. Herein, we report the N-heterocyclic carbene-catalyzed synthesis of axially via desymmetrization prochiral 2-aryloxyisophthalaldehydes with aliphatic alcohols, phenol derivatives, heteroaromatic amines. This reaction features mild conditions, good functional group tolerance, broad substrate scope excellent enantioselectivity. The utility this methodology is illustrated by late-stage functionalization, gram-scale synthesis, diverse enantioretentive transformations. Control experiments DFT calculations support association NHC-catalyzed following kinetic resolution enhance

Language: Английский

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Towards Axially Chiral Pyrazole‐Based Phosphorus Scaffolds by Dipeptide‐Phosphonium Salt Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Jan. 25, 2023

Given the comparatively lower rotational barriers, catalytic asymmetric construction of axially chiral biaryl structures, especially those containing a five-membered heterocycle, still remains challenge. Herein, we described general and modular protocol to access atropisomeric arylpyrazole scaffolds phosphorus unit by dipeptide phosphonium salt catalyzed reaction involving an oxidative central-to-axial chirality conversion. This features excellent yields enantioselectivities, broad substrate scope, low catalyst loading, delivering phosphine compounds.

Language: Английский

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N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution

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

Published: March 15, 2024

Abstract Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral is a long-standing challenge synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction cyclophanes. This transformation occurs through dynamic kinetic resolution (DKR) process convert racemic substrates into macrocycle scaffolds in good high yields with excellent enantioselectivities. The ansa chain length aromatic ring substituent size crucial achieve DKR approach. Controlled experiments DFT calculations were performed clarify process.

Language: Английский

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

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

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N-Heterocyclic Carbene-Catalyzed Highly Enantioselective Macrolactonization to Access Planar-Chiral Macrocycles

Organic Letters, Journal Year: 2024, Volume and Issue: 26(5), P. 1040 - 1045

Published: Jan. 31, 2024

An N-heterocyclic carbene (NHC)-catalyzed atroposelective macrolactonization has been disclosed. This approach affords planar-chiral macrocycles in high yields with excellent enantioselectivities over a broad substrate scope. Controlled experiments suggest that the enantioselectivity might arise from cation–n interaction between acyl azolium and electron-rich moiety substrate. mechanism is supported by density functional theory calculations, which also an important π–π stabilizing transition state.

Language: Английский

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