Direct synthesis of pyridine and pyrimidine derivatives

I. Synthesis of Substituted Pyridine Derivatives via the Ruthenium-Catalyzed Cycloisomerization of 3-Azadienynes. The two-step conversion of various N-vinyl and N-aryl amides to the corresponding substituted pyridines and quinolines, respectively, is described. The process involves the direct conversion of amides, including sensitive N-vinyl amides, to the corresponding trimethylsilyl alkynyl imines followed by a ruthenium-catalyzed protodesilylation and cycloisomerization. A wide range of new alkynyl imines are prepared and readily converted to the corresponding azaheterocycles. II. Single-Step Synthesis of Pyrimidine Derivatives. The single-step conversion of various N-vinyl and N-aryl amides to the corresponding pyrimidine and quinazoline derivatives, respectively, is described. The process involves amide activation with 2-chloropyridine and trifluoromethanesulfonic anhydride followed by nitrile addition into the reactive intermediate and cycloisomerization. In situ nitrile generation from primary amides allows for their use as nitrile surrogates. The use of this chemistry with sensitive N-vinyl amides and epimerizable substrates in addition to a wide range of functional groups is noteworthy. III. Direct Synthesis of Pyridine Derivatives. The single-step conversion of various N-vinyl and N-aryl amides to the corresponding pyridine and quinoline derivatives, respectively, is described. The process involves amide activation with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine followed by t-nucleophile addition to the activated intermediate and annulation. Compatibility of this chemistry with sensitive N-vinyl amides, epimerizable substrates, and a variety of functional groups is noteworthy.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Hill, Matthew D. (Matthew Dennis)

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/1721.1/43776

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/43776