Regioselective synthesis of 3-benzazepinones: Development and understanding of seven-membered ring formation via intramolecular hydroamidation of phenylacetylenes

ORGN 446

David Mitchell, dmit@lilly.com and Ying Yu, yu_ying@lilly.com. Chemical Product Research and Development, Eli Lilly and Company, Indianapolis, IN 46285
Synthesis of 3-benzazepinones by palladium-catalyzed intramolecular addition of amides to alkynes is achieved. The desired seven-membered ring formation was accomplished from 2-alkynyl phenylacetamide in the presence of 5% Pd(OAc)2(PPh3)2 and bases such as KOH or NaOEt. It was found that regioselective 4-alkyl-3-benzazepinone synthesis could be obtained in good yields from 2-alkylethynyl phenylacetamide. A five-membered ring 3-indenecarboxamide was identified as the major by-product, the formation of which was promoted by strong basic and thermal conditions. On the other hand, in the case of 2-arylethynyl and 2-alkenylethynyl phenylacetamide, 3-isoquinolinone derivatives were observed as six-membered ring formation product. The synthesis, methodology along with a mechanistic rationale will be presented.
 

Modern Acetylene Chemistry
8:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006