Direct dehydrative N-Pyridinylation of amides, the interrupted Bischler-Napieralski reaction, and the enantioselective total synthesis and arylative dimerization of aspidosperma alkaloids
Author(s)Medley, Jonathan William
Massachusetts Institute of Technology. Department of Chemistry.
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I. Direct Dehydrative N-Pyridinylation of Amides A method for the single-step N-pyridinylation of secondary amides is described. The process involves electrophilic activation of secondary amides with trifluoromethanesulfonic anhydride in the presence of 2-fluoropyridine followed by introduction of a pyridine N-oxide derivative and warming to afford the corresponding N-pyridinyl tertiary amide derivatives. The structure of activated amide intermediates is probed through in situ monitoring, and a mechanism supported by in situ monitoring and deuterium labeling experiments is discussed. II. Synthesis of Spirocyclic Indolines by Interruption of the Bischler-Napieralski Reaction The development of a versatile method for the synthesis of spirocyclic pyrrolidinoindolines is described. Treatment of N-acyltryptamines with trifluoromethanesulfonic anhydride-2-chloropyridine reagent combination affords highly persistent spiroindoleninium ions, which are selectively trapped intra- and intermolecularly by various nucleophiles. III. A Concise and Versatile Double-Cyclization Strategy for the Highly Stereoselective Synthesis and Novel Arylative Dimerization of Aspidosperma Alkaloids A strategy for the concise, stereoselective synthesis of aspidosperma alkaloids and related structures via a common putative diiminium ion intermediate is described. The approach enables the dimerization of aspidosperma-type structures at the sterically hindered C2-position. The diiminium intermediate is prepared in situ from an enantioenriched [alpha]-quaternary 2- chlorotryptamine lactam through a stereoselective electrophilic double-cyclization cascade. The key C5-quaternary stereocenter is secured via successive diastereoselective [alpha]-alkylations of pseudoephenamine crotonamide.
Thesis (Ph. D. in Organic Chemistry)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013.Cataloged from PDF version of thesis. Vita.Includes bibliographical references.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology