Direct dehydrative N-Pyridinylation of amides, the interrupted Bischler-Napieralski reaction, and the enantioselective total synthesis and arylative dimerization of aspidosperma alkaloids

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2013

Author dc:creator

• Medley, Jonathan William

Advisor dc:contributor.advisor

• Mohammad Movassaghi.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/82319

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/82319