Synthesis of nitrogen heterocycles via the intramolecular [4+2] cycloaddition of iminoacetonitriles

Iminoacetonitriles have been shown to function as aza dienophiles in intramolecular Diels-Alder reactions, affording substituted quinolizidines and indolizidines. The cycloadducts are formed with a high preference for an exo-orientated cyano group due to the a-amino nitrile anomeric effect. The substrates for these [4+2] cycloadditions are prepared from readily available alcohols via a Mitsunobu reaction with the previously unknown N-cyanomethyltriflamide (HN(Tf)CH₂CN) followed by cesium carbonate promoted elimination of trifluoromethanesulfinate. The a-amino nitrile cycloadducts are versatile synthetic intermediates and can be elaborated via alkylation, reduction, and nucleophilic addition chemistry to provide a variety of substituted and functionalized nitrogen heterocycles. Initial investigations have been undertaken to explore the use of this methodology in the total synthesis of alkaloid natural products.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Amos, David Thomas, 1975-

Advisor dc:contributor.advisor

• Rick L. Danheiser.

• 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/1721.1/30015

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/30015