Catalytic Enantioselective Macrocyclization for the Synthesis of Planar‐Chiral Cyclophanes: Recent Updates

Dong, Ziyang; Li, Jia; Zhao, Changgui

doi:10.1002/ejoc.202400841

Cited by 3 publications

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Enantioselective Construction of Planar‐Chiral Molecules by Catalytic Asymmetric Late‐Stage Functionalizations

Zhao,

Zhu,

Chen

2024

ChemCatChem

View full text Add to dashboard Cite

Planar chirality, as one of the most important manifestations of chirality, is frequently employed to constrain three‐dimensional chiral configurations. Recent advancements in the study of planar chirality by chemists have opened up innovative possibilities for designing new catalysts, developing novel drugs, and creating new optical materials. However, the flexible ansa chains present a challenge during the synthesis process of these unique planar‐chiral macrocycles, hindering chemists from achieving high enantioselectivity. In this mini review, we primarily introduce the catalytic asymmetric synthesis methods that have been reported for late‐stage functionalization of planar macrocycles to generate planar chirality. Additionally, we present several recent examples of catalytic enantioselective synthesis of mechanically planar‐chiral rotaxanes through late‐stage functionalization methods. The sources of stereoselectivity are also discussed in this mini review. We aim to inform more researchers about this field and attract chemists to engage in this important and scientifically significant area of research.

show abstract

Enantioselective Construction of Planar‐Chiral Molecules by Catalytic Asymmetric Late‐Stage Functionalizations

Zhao,

Zhu,

Chen

2024

ChemCatChem

View full text Add to dashboard Cite

show abstract

Rhodium(III)-Catalyzed Atroposelective Indolization to Access Planar-Chiral Macrocycles

Zhai,

Lv,

et al. 2024

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Macrocycles incorporating conformationally defined indoles are widely found in bioactive natural products. However, the catalytic enantioselective synthesis of planar-chiral indoles via indolization involving macrocyclization remains elusive. Herein, we present the first rhodium(III)-catalyzed atroposelective macrocyclization, which involves the C−H activation of aniline, and a subsequent oxidation [3 + 2] annulation reaction with an intramolecular alkyne. This protocol achieves the construction of indoles, macrocyclization, and planar chirality control in a single step. Importantly, this strategy produces macrocyclic atropisomers bearing full-carbon ansa chains, which represent challenging targets in organic synthesis. Thermodynamic experiments revealed that the rotational barrier of the full-carbon ansa chain-linked macrocyclic atropisomer was lower than that of the atropisomer bearing an oxaansa chain. The reaction mechanism was elucidated by computational studies, which revealed that the C−H activation and intramolecular alkyne insertion steps collectively determined the enantioselectivity.

show abstract

Conformationally Defined Planar-Chiral [n]Paracyclophanes Stabilized by Chiral Ansa Chains

Zhao,

Wang,

Wen

et al. 2025

Preprint

View full text Add to dashboard Cite

Although chiral substituents have been incorporated into ansa chains to stabilize the conformations of cyclophanes and modulate the biological activities of pharmaceuticals, the asymmetric syntheses of these atropisomers relies on substrate-induced diastereoselective macrocyclization. Consequently, enantio-, atrop-, and diastereoselective macrocyclizations are yet to be reported. Herein, we describe a N-heterocyclic carbene (NHC) and chiral phosphoric acid (CPA) dual-catalytic process for the desymmetrization of 1,3-diols, to achieve macrocyclization and stereoselective control over two chiral elements. It was deduced that the hydrogen bonding of CPA with the 1,3-diols enhanced the diastereoselectivity of the process. As a result, various planar-chiral cyclophanes bearing chiral ansa chains were synthesized. Thermodynamic experiments revealed that the presence of an all-carbon quaternary carbon center on the ansa chain significantly increased the rotational barriers of the cyclophanes. Moreover, density functional theory calculations suggested that the chiral substituent shrinks the ansa chain by compressing the bond angle, thereby rendering the conformational rotation reaction more challenging.

show abstract

Catalytic Enantioselective Macrocyclization for the Synthesis of Planar‐Chiral Cyclophanes: Recent Updates

Cited by 3 publications

References 103 publications

Enantioselective Construction of Planar‐Chiral Molecules by Catalytic Asymmetric Late‐Stage Functionalizations

Enantioselective Construction of Planar‐Chiral Molecules by Catalytic Asymmetric Late‐Stage Functionalizations

Rhodium(III)-Catalyzed Atroposelective Indolization to Access Planar-Chiral Macrocycles

Conformationally Defined Planar-Chiral [n]Paracyclophanes Stabilized by Chiral Ansa Chains

Contact Info

Product

Resources

About