Asymmetric Synthesis of Nonbiaryl Atropisomers

Saputra, Mirza A.; Cardenas, Mariel M.; Gustafson, Jeffrey L.

doi:10.1002/9783527825172.ch5

“…While traditional resolution methods can furnish enantiopure samples from racemic mixtures, they can often be time-consuming, resource-intensive, and not practical in the context of structure optimization. These challenges have been given a recent spotlight as more class-3 atropisomers make it to the clinic, often requiring heroic efforts to meet the challenges of material throughput. , While atroposelective methods have been studied for decades, they have largely focused on biaryls, leaving relatively few methodologies ,− that are applicable to the other pharmaceutically relevant scaffolds. This has led our group to embark on a series of projects that focus on the development of atropisomer-selective methodologies toward pharmaceutically relevant scaffolds.…”

Section: Atropisomer Selective Synthesis Of Pharmaceutically Relevant...mentioning

confidence: 99%

Atropisomerism in the Pharmaceutically Relevant Realm

Basilaia

¹

,

Chen

²

,

Secka

³

et al. 2022

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Metrics & MoreArticle Recommendations * sı Supporting Information CONSPECTUS: Atropisomerism is a conformational chirality that occurs when there is hindered rotation about a σ-bond. While atropisomerism is exemplified by biaryls, it is observed in many other pharmaceutically relevant scaffolds including heterobiaryls, benzamides, diarylamines, and anilides. As bond rotation leads to racemization, atropisomers span the gamut of stereochemical stability. LaPlante has classified atropisomers based on their halflife of racemization at 37 °C: class 1 (t 1/2 < 60 s), class 2 (60 s < t 1/2 < 4.5 years), and class 3 (t 1/2 > 4.5 years). In general, class-3 atropisomers are considered to be suitable for drug development.

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Enantioselective Synthesis of Heteroatom‐Linked Non‐Biaryl Atropisomers

Naghim,

Rodriguez,

Chuzel

et al. 2024

Angewandte Chemie

0

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Atropisomers hold significant fascination, not only for their prevalence in natural compounds but also for their biological importance and wide‐ranging applications as chiral materials, ligands, and organocatalysts. While biaryl and heterobiaryl atropisomers are commonly studied, the enantioselective synthesis of less abundant heteroatom‐linked non‐biaryl atropisomers presents a formidable challenge in modern organic synthesis. Unlike classical atropisomers, these molecules allow rotation around two bonds, resulting in low barriers to enantiomerization through concerted bond rotations. In recent years the discovery of new configurationally stable rare non‐biaryl scaffolds such as aryl amines, aryl ethers and aryl sulfones as well as innovative methodologies to control their configuration have been disclosed in the literature and constitute the topic of this minireview.

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Enantioselective Synthesis of Heteroatom‐Linked Non‐Biaryl Atropisomers

Naghim,

Rodriguez,

Chuzel

et al. 2024

Angew Chem Int Ed

5

0

View full text Add to dashboard Cite

Atropisomers hold significant fascination, not only for their prevalence in natural compounds but also for their biological importance and wide‐ranging applications as chiral materials, ligands, and organocatalysts. While biaryl and heterobiaryl atropisomers are commonly studied, the enantioselective synthesis of less abundant heteroatom‐linked non‐biaryl atropisomers presents a formidable challenge in modern organic synthesis. Unlike classical atropisomers, these molecules allow rotation around two bonds, resulting in low barriers to enantiomerization through concerted bond rotations. In recent years the discovery of new configurationally stable rare non‐biaryl scaffolds such as aryl amines, aryl ethers and aryl sulfones as well as innovative methodologies to control their configuration have been disclosed in the literature and constitute the topic of this minireview.

show abstract

Asymmetric Synthesis of Nonbiaryl Atropisomers

Cited by 3 publications

References 96 publications

Atropisomerism in the Pharmaceutically Relevant Realm

Atropisomerism in the Pharmaceutically Relevant Realm

Enantioselective Synthesis of Heteroatom‐Linked Non‐Biaryl Atropisomers

Enantioselective Synthesis of Heteroatom‐Linked Non‐Biaryl Atropisomers

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