Molecular Dynamics Investigations of Dienolate [4 + 2] Reactions

Chen, Peng-Jui; Cusumano, Alexander Q.; Flesch, Kaylin N.; Strong, Christian Santiago; Goddard, William A.; Stoltz, Brian M.

doi:10.1021/jacs.4c02681

J. Am. Chem. Soc.

2024

DOI: 10.1021/jacs.4c02681

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Molecular Dynamics Investigations of Dienolate [4 + 2] Reactions

Peng-Jui Chen,

Alexander Q. Cusumano,

Kaylin N. Flesch

et al.

Abstract: We report quantum mechanics calculations and quasiclassical trajectory simulations of [4 + 2] reactions using three common dienolate substrates: siloxy dienes, Li dienolates, and conjugated Pd enolates. Asynchronous transition structures and unequal bond formation were invariably found, with average time gaps of developing bonds ranging from 26.5 to >251.0 fs. The results display a spectrum of dynamically concerted and stepwise [4 + 2] reactions, offering insights into the origin of the stereochemical outcomes… Show more

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Bi(OTf)₃-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines

Punjajom,

Chonradeenitchakul,

Tummatorn

et al. 2024

Org. Lett.

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An unprecedented Bi(OTf) 3 -catalyzed reaction between 2-arylisatogens and vinylarenes to yield 2,4-diarylquinolines is reported. The transformation occurred via a Bi III -coordination to the embedded anionic nitrone oxygen, which induced a regiospecific stepwise formal [4 + 2]-cycloaddition with vinylarenes to yield a strained tricyclic intermediate, which subsequently extruded gaseous carbon monoxide. N-Deoxygenative aromatization ensued to produce 2,4-diarylquinolines. The protocol was applicable to a variety of substrates to produce the quinolines in up to an 89% yield.

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Bi(OTf)₃-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines

Punjajom,

Chonradeenitchakul,

Tummatorn

et al. 2024

Org. Lett.

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Mechanistic Investigation of the Pseudo-Halogen Effect in Enantioselective Aminocatalyzed [6 + 4] and [10 + 6] Cycloadditions: Enabling Unique Favorskii-Like Rearrangements

Barløse,

Bitsch,

Faghtmann

et al. 2024

J. Am. Chem. Soc.

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A mechanistic investigation into the novel combination of the pseudo-halogen effect with enantioselective aminocatalysis unravels the mechanistic intricacies of [6 + 4] and [10 + 6] higher-order cycloadditions and the succeeding new Favorskii-like rearrangements. By introducing the OTf-group into the tropone framework, it can serve both as an activator for the cycloaddition and as a proficient leaving group within the corresponding cycloadduct, thus enabling unprecedented ring-contracting Favorskii-like rearrangements. Integrating the -OTf group creates an electron-deficient 6π-component leveraging the pseudo-halogen effect by enhancing the polarization and introducing new strategic interaction points. This modification complements electron-rich 4π-and 10π-components from amino-activated 2,4-dienals or indene-carbaldehydes. A comprehensive DFT investigation supported by experimental results demonstrates that the [6 + 4] system proceeds through a rate-limiting stepwise exo-cycloaddition leading to a cycloadduct initially in a boat-conformation, subsequently transitioning to the more stable chair-conformation. The change in conformation ensures an S N 1-like expulsion of the -OTf group, generating a stable carbocation bridgehead primed for a novel Favorskii-like seven-to-six ring-contracting rearrangement, resulting in the experimentally observed product. As proof-of-concept for the cycloaddition/Favorskii-like rearrangement, it is demonstrated that this approach can be extended to an unprecedented [10 + 6] cycloaddition. In contrast to the [6 + 4] system, the [10 + 6] system distinguishes itself with a concerted S N 1-like/Favorskii-like six-to-five ring-contracting rearrangement, representing the rate-limiting step. This novel concept results in the experimental isolation of structurally complex products in high peri-, diastereo-, and enantioselectivity with moderate yield. These findings demonstrate the pseudo-halogen effect's multifaceted role in promoting and enabling novel reactivity.

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Molecular Dynamics Investigations of Dienolate [4 + 2] Reactions

Cited by 2 publications

References 47 publications

Bi(OTf)₃-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines

Bi(OTf)₃-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines

Mechanistic Investigation of the Pseudo-Halogen Effect in Enantioselective Aminocatalyzed [6 + 4] and [10 + 6] Cycloadditions: Enabling Unique Favorskii-Like Rearrangements

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Molecular Dynamics Investigations of Dienolate [4 + 2] Reactions

Cited by 2 publications

References 47 publications

Bi(OTf)3-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines

Bi(OTf)3-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines

Mechanistic Investigation of the Pseudo-Halogen Effect in Enantioselective Aminocatalyzed [6 + 4] and [10 + 6] Cycloadditions: Enabling Unique Favorskii-Like Rearrangements

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Product

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Bi(OTf)₃-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines

Bi(OTf)₃-Catalyzed Cascade Cycloaddition–Decarbonylation–N-Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines