Synthesis of highly substituted indolines and indoles via intramolecular [4 + 2] cycloaddition of ynamides and conjugated enynes.
Ynamides react with conjugated enynes in intramolecular [4 + 2] cycloadditions 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 2pi components in the cycloaddition, providing access to indolines with carbon substituents at the C-7 position. Enynamides serve as 4pi components in a complementary version of the cycloaddition strategy which provides access to indoles and indolines substituted with carbon substituents at C-4. These enyne cycloadditions take place upon heating the substrates at 110-210 degrees C in toluene or 2,2,2-trifluoroethanol and in some cases can be achieved at 0 degrees C to room temperature in the presence of Lewis acids such as Me2AlCl.
Dunetz
Joshua R
JR
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Danheiser
Rick L
RL
D000480:Alkynes / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis*
D000480:Alkynes; D000577:Amides; D007211:Indoles