Synthesis of indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes ; Synthesis of nitrogen heterocycles in supercritical carbon dioxide

A general amination strategy for the N-alkynylation of carbamates, sulfonamides, and chiral oxazolidinones and imidazolidinones is described. A variety of substituted ynamides are available by deprotonation of amide derivatives with KHMDS followed by reaction with CuI and an alkynyl halide. Ynamides react with conjugated enynes in intramolecular [4 + 2] cycloaddition to afford substituted indolines that undergo oxidation with o-chloranil to furnish the corresponding indoles. The cycloaddition substrates are easily assembled from derivatives of 3-butynylamine by Sonogashira coupling with alkenyl halides followed by copper-catalyzed N-alkynylation with acetylenic bromides. Diynamides participate as particularly reactive 2[pi] components in the cycloaddition, providing access to indolines with carbon substituents at the C-7 position. Enynamides serve as 4[pi] components in a complementary version of the cycloaddition strategy which provides access to indoles and indolines substituted with substituents at C-4. These enyne cycloadditions take place upon heating the substrates at 110-210⁰C in toluene or 2,2,2- trifluoroethanol and in some cases can be achieved at 0⁰C to room temperature in the presence of Lewis acids such as Me₂A1C1.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Dunetz, Joshua Ross

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/1721.1/33650

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/33650