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Diversification of Nucleophile-Intercepted Beckmann Fragmentation Products and Related Density Functional Theory Studies.

ABSTRACT: The nucleophile-intercepted Beckmann fragmentation (NuBFr) has the potential to be broadly applicable to the synthesis of indoline alkaloid-based natural products. However, the reaction has not been widely adopted, in part, because of limitations associated with the availability of appropriate promoter-Nu reagents. We have devised a stereospecific Ag(I)-promoted reaction for functionalizing NuBFr products to give novel compositions of matter that may be useful in synthesis and medicinal chemistry. With unhindered amine nucleophiles, structurally unique [2.2.2]-bicycloamidines are generated. We also disclose for the first time detailed density functional theory studies, which shed light on the mechanism of the NuBFr and Ag-promoted substitution reaction that supports an unusual aziridinium ion as a key intermediate.

SUBMITTER: Lowder LL

PROVIDER: S-EPMC7485623 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Diversification of Nucleophile-Intercepted Beckmann Fragmentation Products and Related Density Functional Theory Studies.

Lowder Leah L LL Zhao Fengyue F Vaughan Mathes M MM Houk K N KN Liu Fang F Wu Jimmy J

The Journal of organic chemistry 20200826 17

The nucleophile-intercepted Beckmann fragmentation (NuBFr) has the potential to be broadly applicable to the synthesis of indoline alkaloid-based natural products. However, the reaction has not been widely adopted, in part, because of limitations associated with the availability of appropriate promoter-<b>Nu</b> reagents. We have devised a stereospecific Ag(I)-promoted reaction for functionalizing NuBFr products to give novel compositions of matter that may be useful in synthesis and medicinal c ...[more]

PMID: 32786611

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