Catalytic Enantioselective Synthesis of C–N Atropisomeric Heterobiaryls DOI
Peter C. Knipe, Jamie S. Sweet

Synthesis, Journal Year: 2022, Volume and Issue: 54(09), P. 2119 - 2132

Published: Feb. 23, 2022

Abstract Molecules containing an atropisomeric C–N biaryl axis are gaining increasing attention in catalytic and medicinal chemistry. Despite this rising interest, relatively few approaches towards their enantioselective synthesis have been reported. Here we review these approaches, with a focus on the mechanism of asymmetric induction. Some common themes emerge: Brønsted acid catalysed cyclo-condensation palladium-catalysed ring-closure most successful approaches. Meanwhile, more direct but challenging axial bond formation strategy remains its infancy, just two reports to-date. We hope will inform inspire other researchers to develop new creative important chemical motif. 1 Introduction 2 Cyclo-Condensation 3 Proximal Bond Formation 4 Desymmetrisation Intact Axes 5 ortho-C–H Functionalisation 6 Cycloaddition 7 Axial 8 Atropisomeric N–N Axes: An Emerging Class Heterobiaryls 9 Conclusion Outlook

Language: Английский

Atropisomers beyond the C–C axial chirality: Advances in catalytic asymmetric synthesis DOI Creative Commons
Guang‐Jian Mei, Wai Lean Koay,

Chun-Yan Guan

et al.

Chem, Journal Year: 2022, Volume and Issue: 8(7), P. 1855 - 1893

Published: May 6, 2022

Language: Английский

Citations

255
Asymmetric Synthesis of Axially Chiral C−N Atropisomers DOI Creative Commons
Patricia Rodríguez‐Salamanca, Rosario Fernández, Valentı́n Hornillos

et al.

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(28)

Published: Feb. 22, 2022

Molecules with restricted rotation around a single bond or atropisomers are found in wide number of natural products and bioactive molecules as well chiral ligands for asymmetric catalysis smart materials. Although most these compounds biaryls heterobiaryls displaying C-C stereogenic axis, there is growing interest less common more challenging axially C-N atropisomers. This review offers an overview the various methodologies available their synthesis. A brief introduction initially given to contextualize skeletons, including historical background examples containing axes. The preparation different families based then presented from anilides five- six-membered ring heterocycles. Special emphasis has been modern catalytic strategies over past decade synthesis scaffolds. Applications methods biologically active will be highlighted along text.

Language: Английский

Citations

149
Rational design and atroposelective synthesis of N–N axially chiral compounds DOI Creative Commons
Guang‐Jian Mei, Jonathan J. Wong, Wenrui Zheng

et al.

Chem, Journal Year: 2021, Volume and Issue: 7(10), P. 2743 - 2757

Published: Aug. 18, 2021

Language: Английский

Citations

122
Catalytic Asymmetric Synthesis of Axially Chiral 3,3'‐Bisindoles by Direct Coupling of Indole Rings DOI

Feng‐Tao Sheng,

Shuang Yang, Shufang Wu

et al.

Chinese Journal of Chemistry, Journal Year: 2022, Volume and Issue: 40(18), P. 2151 - 2160

Published: May 31, 2022

Comprehensive Summary A new strategy for the enantioselective synthesis of axially chiral 3,3'‐bisindoles was devised by direct coupling two indole rings. This makes use C3‐umpolung reactivity 2‐indolylmethanols, which enables catalytic asymmetric addition reaction 2‐indolylmethanols with rationally designed 2‐substituted indoles, thus constructing 3,3'‐bisindole scaffolds in overall excellent yields (up to 98%) high enantioselectivities 96 : 4 er). approach not only has overcome challenges five‐five‐membered heterobiaryls, but also represents a application catalysis. More importantly, this class can undergo variety post‐functionalizations give 3,3'‐bisindole‐based organocatalysts, have found their preliminary applications

Language: Английский

Citations

111
Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles DOI

Zhi‐Han Chen,

Tian‐Zhen Li,

Ning‐Yi Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 7, 2023

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N'-bisindoles via phosphoric acid-catalyzed formal (3+2) cycloadditions indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various were synthesized in good yields and excellent enantioselectivities (up to 87 % yield 96 ee). More importantly, class exhibited some degree cytotoxicity toward cancer cells was derived into phosphine ligands high catalytic activity. provides a strategy for using asymmetric organocatalysis realize applications such scaffolds medicinal chemistry catalysis.

Language: Английский

Citations

90
Synthesis of Axially ChiralN‐Arylindoles via Atroposelective Cyclization of Ynamides Catalyzed by Chiral Brønsted Acids DOI
Ze‐Shu Wang,

Lu‐Jing Zhu,

Cui‐Ting Li

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(20)

Published: March 5, 2022

In recent years, asymmetric catalysis of ynamides has attracted much attention, but these reactions mostly constructed central chirality, except for a few examples on the synthesis axially chiral compounds which exclusively relied noble-metal catalysis. Herein, facile access to N-heterocycles enabled by Brønsted acid-catalyzed 5-endo-dig cyclization is disclosed, represents first metal-free protocol construction from ynamides. This method allows practical and atom-economical valuable N-arylindoles in excellent yields with generally enantioselectivities. Moreover, organocatalysts ligands based such N-arylindole skeletons are demonstrated be applicable

Language: Английский

Citations

83
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

77
Enantioselective Synthesis of N−N Bisindole Atropisomers DOI
Peng Zhang, Qi Xu, Xiaomei Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(44)

Published: Sept. 15, 2022

N-N Atropisomers are a common motif in natural products and represent significant dimension for exploration modern pharmaceutical medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective bisindole atropisomers is unprecedented. Herein, first via palladium-catalyzed de novo construction one indole skeleton presented. A wide variety axially chiral bisindoles were generated good yields with excellent enantioselectivities cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indole-carbazole, non-biaryl-indole possessing axis accessed using this protocol. Moreover, investigations density functional theory (DFT) calculations provided insight into reaction mechanism enantiocontrol.

Language: Английский

Citations

76
Design and catalytic atroposelective synthesis of axially chiral isochromenone-indoles DOI
Qing‐Qing Hang, Shufang Wu, Shuang Yang

et al.

Science China Chemistry, Journal Year: 2022, Volume and Issue: 65(10), P. 1929 - 1937

Published: Sept. 13, 2022

Language: Английский

Citations

76
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

17