Open AccessDiversification of Nucleophile-Intercepted Beckmann Fragmentation Products and Related Density Functional Theory Studies
Author(s) -
Leah L. Lowder,
Fubo Zhao,
Mathes M. Vaughan,
K. N. Houk,
Fang Liu,
Jimmy Wu
Publication year - 2020
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.0c01486
Subject(s) - nucleophile , indoline , chemistry , fragmentation (computing) , stereospecificity , beckmann rearrangement , reagent , amine gas treating , combinatorial chemistry , stereochemistry , organic chemistry , biology , ecology , oxime , catalysis
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.