Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage

Roos, Casey B.; Chiang, Chang-Hwa; Murray, Lauren A. M.; Yang, Di; Schulert, Luke; Narayan, Alison R. H.

doi:10.1021/acs.chemrev.3c00327

Cited by 27 publications

(9 citation statements)

References 343 publications

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“…These properties are consistent with the known hemiboronic phenanthroids . Moreover, density functional theory (DFT) calculations on the dynamic properties of 1a revealed that the rotational barrier was only 4.34 kcal/mol, indicating fast interconversion between ( R )- 1a and ( S )- 1a at ambient temperature, which lays the foundation for the desired dynamic kinetic asymmetric transformations …”

Section: Resultsmentioning

confidence: 99%

Developing Biarylhemiboronic Esters for Biaryl Atropisomer Synthesis via Dynamic Kinetic Atroposelective Suzuki–Miyaura Cross-Coupling

Yang,

Wu,

Xing

et al. 2024

J. Am. Chem. Soc.

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We herein introduce biarylhemiboronic esters as a new type of bridged biaryl reagent for asymmetric synthesis of axially chiral biaryl structures, and the palladium-catalyzed asymmetric Suzuki−Miyaura cross-coupling of biarylhemiboronic esters is developed. This dynamic kinetic atroposelective coupling reaction exhibits high enantioselectivity, good functional group tolerance, and a broad substrate scope. The synthetic application of the current method was demonstrated by transformations of the product and a programmed synthesis of chiral polyarene. Preliminary mechanistic studies suggested that the reaction proceeded via an enantio-determining dynamic kinetic atroposelective transmetalation step.

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Section: Resultsmentioning

confidence: 99%

Developing Biarylhemiboronic Esters for Biaryl Atropisomer Synthesis via Dynamic Kinetic Atroposelective Suzuki–Miyaura Cross-Coupling

Yang,

Wu,

Xing

et al. 2024

J. Am. Chem. Soc.

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“…Atropisomers are commonly observed in natural products, pharmaceutical agents, agricultural chemicals, and functional materials [13–17] . The recent exploration of catalytic atroposelective synthesis has opened up exciting opportunities for preparing axially chiral compounds with high levels of stereocontrol [18–24] …”

Section: Introductionmentioning

confidence: 99%

Catalytic Synthesis of Atropoisomers via Non‐Canonical Friedel‐Crafts Reactions

Ye,

Yu,

Deng

et al. 2024

Adv Synth Catal

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The Friedel‐Crafts reaction stands as a powerful synthetic tool for C‐H functionalization of aromatic feedstocks, which is conventionally realized through electrophilic alkylation and acylation. The burgeoning interests in axially chiral compounds across diverse fields have spurred extensive exploration of this classic transformation for catalytic atroposelective synthesis. Consequently, the past decade has witnessed the rapid expansion of various non‐canonical Friedel‐Crafts reactions, including electrophilic arylation, alkenylation, halogenation, sulfenylation, and amination of aryl C‐H bonds, thereby delving into new chemical spaces. A range of catalytic atroposelective synthetic methods have been devised for these significant arene C‐H functionalization. This review provides a comprehensive overview of the cutting‐edge catalytic synthesis of atropoisomers through non‐canonical Friedel‐Crafts reactions, categorized into three parts based on the type of bond formation on the aromatics: C(sp2)‐C(sp3) bond formations, C(sp2)‐C(sp2) bond formations and C(sp2)‐heteroatom bond formations. The richness of electrophiles and the modulation of atroposelectivity by diverse chiral organocatalysts, particularly chiral Brønsted acids, are elucidated. We anticipate that the repertoire of asymmetric Friedel‐Crafts reaction will continue to flourish and to be demonstrated in not only scientific researches but also industrial organic synthesis.

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“…Organic axially chiral compounds, with hindered rotation along a single bond, have received increasing attention in the past decades owing to their outstanding properties as natural products, bioactive molecules, and chiral ligands . In contrast to the most abundant category of C–C axially chiral biaryls that have been predominantly studied, C–N axially chiral biaryls remain underexplored. Nevertheless, this chiral motif is widely present and may outperform the C–C counterpart as functional molecules in natural product chemistry, drug design, and asymmetric catalysis (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Intermolecular Buchwald–Hartwig Reactions for Enantioselective Synthesis of Diverse Atropisomers: Rerouting the C–N Forming Mechanism to Substrate Oxygen-Assisted Reductive Elimination

Wang,

Jiang,

et al. 2024

J. Am. Chem. Soc.

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Axially chiral biaryls featuring a C−N axis are important functional molecules in diverse fields. The asymmetric Buchwald−Hartwig reaction represents a powerful strategy for these targets. Previous studies, however, have been predominantly restricted to intramolecular atroposelective coupling, likely due to the steric and entropic effects in the reductive elimination of Pd(II) species with sterically congested aryl and nitrogen groups. We now report two intermolecular Buchwald−Hartwig coupling systems of bulky NH lactams and halohydrocarbons enabled by rerouting the mechanism of C−N reductive elimination to one that accommodates sterically challenging substrates. Both atroposelective coupling systems exhibited functional group tolerance, excellent enantioselectivity, and high Z selectivity (if applicable), affording C− N atropisomeric biaryl and olefins through de novo construction of a C−N chiral axis. Experimental and computational studies were performed to elucidate the mechanism, and the switch of the reaction pathways is traced to the steric effect (ortho substituent) of the aryl halide substrate. A bulky 2,6-disubstituted aryl halide reorients the proximal lactamide ligand to its unusual O-ligation mode. With the amide oxygen participation, this intermediate undergoes C−N reductive elimination with an accessible barrier through a five-membered ring transition state, a pathway as well as a chiral induction mode that has been much underexplored in asymmetric catalysis.

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Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage

Cited by 27 publications

References 343 publications

Developing Biarylhemiboronic Esters for Biaryl Atropisomer Synthesis via Dynamic Kinetic Atroposelective Suzuki–Miyaura Cross-Coupling

Developing Biarylhemiboronic Esters for Biaryl Atropisomer Synthesis via Dynamic Kinetic Atroposelective Suzuki–Miyaura Cross-Coupling

Catalytic Synthesis of Atropoisomers via Non‐Canonical Friedel‐Crafts Reactions

Intermolecular Buchwald–Hartwig Reactions for Enantioselective Synthesis of Diverse Atropisomers: Rerouting the C–N Forming Mechanism to Substrate Oxygen-Assisted Reductive Elimination

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