Atroposelective Synthesis of Axially Chiral Styrenes Connecting an Axially Chiral Naphthyl-indole Moiety Using Chiral Phosphoric Acid Catalysis

Woldegiorgis, Alemayehu Gashaw; Gu, Haorui; Lin, Xufeng

doi:10.1021/acs.orglett.3c00425

Cited by 12 publications

(4 citation statements)

References 35 publications

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“…Very recently, Lin reported the chiral phosphoric acid catalyzed enantioselective Friedel-Crafts alkenylation of 3-naphthyl-indoles 81 with o-alkynylnaphthol 80, realizing the atroposelective synthesis of axially chiral styrenes bonded to an axially chiral element (Scheme 23C). [96] Under the mild condition, a range of such axially chiral styrenes were obtained in good yields with up to 99.9% ee, > 20 : 1 dr and > 99 : 1 E/ Z. The reaction could be easy scalable with almost same yields and stereoselectivities as small scale.…”

Section: Formation Of Arylalkene Atropisomersmentioning

confidence: 90%

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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Section: Formation Of Arylalkene Atropisomersmentioning

confidence: 90%

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

Ye,

Yu,

Deng

et al. 2024

Adv Synth Catal

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“…In 2023, Lin and co-workers 85 reported the first asymmetric reactions between C2-unsubstituted racemic naphthylindoles 74 and orthoalkynyl naphthols 69 catalyzed by SPINOL-CPA (CPA 20). This novel strategy enabled the atroposelective synthesis of a complex organic framework via dynamic kinetic resolution that linked axially chiral styrenes with axially chiral naphthyl-indoles 78 (Scheme 22).…”

Section: Vinylidene Quinone Methide (Vqm) As Electrophilementioning

confidence: 99%

Stereoselective Synthesis of Axially Chiral Allenes and Styrenes via Chiral Phosphoric Acid Catalysis: An Overview

Woldegiorgis,

Mustafai,

Muhammad

et al. 2024

ACS Omega

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Chiral allenes and styrenes are essential components in fields like medicinal chemistry, materials science, and organic synthesis. They serve a crucial role as chiral ligands and catalysts in asymmetric synthesis. Over the past decade, there has been a significant advancement in the development of practical methods utilizing organocatalytic strategies for the synthesis of chiral allenes and styrenes. It is noteworthy that despite extensive studies on the formation of allenes and styrenes, existing reviews on their construction confined to a specific organocatalysis, called chiral phosphoric acid catalysis, are less documented. This review aims to explore different conceptual approaches based on the electrophilic species involved in the reaction to produce stereoselective chiral allenes and styrenes, providing insights into recent advancements in the field. Emphasis is placed on works published since 2017, with detailed discussions on reaction mechanisms and examples from recent literature.

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“…Axially chiral indole-based scaffolds, a class of unique axially chiral skeletons, − are widely found in natural products, − pharmaceutically relevant molecules, − and chiral catalysts. − Therefore, catalytic asymmetric construction of axially chiral indole-based scaffolds has become an emerging field. , As shown in Scheme a, various elegant strategies have been developed for the enantioselective construction of axially chiral (hetero)arylindoles, such as five-six-membered axially chiral arylindoles ,− and five-five-membered axially chiral (hetero)arylindoles. ,,− However, in sharp contrast, axially chiral alkenylindoles, more challenging axially chiral...…”

Section: Introductionmentioning

confidence: 99%

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

Yang,

Huang,

Wang

et al. 2024

Precision Chemistry

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The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via chiral phosphoric acid-catalyzed addition reactions of C3-unsubstituted 2-alkenylindoles with o-hydroxybenzyl alcohols under different reaction conditions. Using this strategy, two series of 2-alkenylindoles bearing both axial and central chirality were synthesized in a diastereodivergent fashion with moderate to high yields and good stereoselectivities (up to 99% yield, 95:5 er, >95:5 dr). Moreover, theoretical calculations were performed on the key transition states leading to different stereoisomers, which provided an in-depth understanding of the origin of the observed stereoselectivity and diastereodivergence of the products under different reaction conditions. More importantly, these 2-alkenylindoles were utilized in asymmetric catalysis as chiral organocatalysts and in medicinal chemistry for evaluation of their cytotoxicity, which demonstrated their potential applications. This study has not only established the catalytic atroposelective synthesis of axially chiral 2-alkenylindoles, but also provided an efficient strategy for catalytic asymmetric diastereodivergent construction of indole-based scaffolds bearing both axial and central chirality.

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Atroposelective Synthesis of Axially Chiral Styrenes Connecting an Axially Chiral Naphthyl-indole Moiety Using Chiral Phosphoric Acid Catalysis

Cited by 12 publications

References 35 publications

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

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

Stereoselective Synthesis of Axially Chiral Allenes and Styrenes via Chiral Phosphoric Acid Catalysis: An Overview

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

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