Direct Observation of Intermediates Involved in the Interruption of the Bischler–Napieralski Reaction
Author(s)White, Kolby L.; Mewald, Marius; Movassaghi, Mohammad
MetadataShow full item record
The first mechanistic investigation of electrophilic amide activation of α,α-disubstituted tertiary lactams and the direct observation of key intermediates by in situ FTIR, 1H, 13C, and 19F NMR in our interrupted Bischler–Napieralski-based synthetic strategy to the aspidosperma alkaloids, including a complex tetracyclic diiminium ion, is discussed. The reactivity of a wide range of pyridines with trifluoromethanesulfonic anhydride was systematically examined, and characteristic IR absorption bands for the corresponding N-trifluoromethanesulfonylated pyridinium trifluoromethanesulfonates were assigned. The reversible formation of diiminium ether intermediates was studied, providing insight into divergent mechanistic pathways as a function of the steric environment of the amide substrate and stoichiometry of reagents. Importantly, when considering base additives during electrophilic amide activation, more hindered α-quaternary tertiary lactams require the use of non-nucleophilic pyridine additives in order to avoid deactivation via a competing desulfonylation reaction. The isolation and full characterization of a tetracyclic iminium trifluoromethanesulfonate provided additional correlation between in situ characterization of sensitive intermediates and isolable compounds involved in this synthetic transformation.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Journal of Organic Chemistry
American Chemical Society (ACS)
White, Kolby L., Marius Mewald, and Mohammad Movassaghi. “Direct Observation of Intermediates Involved in the Interruption of the Bischler?Napieralski Reaction.” The Journal of Organic Chemistry 80.15 (2015): 7403–7411.
Author's final manuscript