Work

Synthesis of Highly Substituted Indolines and Indoles via Intramolecular [4 + 2] Cycloaddition of Ynamides and Conjugated Enynes

Year: 2005

Type: article

Abstract: 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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja051180l

Authors: Joshua R. Dunetz, Rick L. Danheiser

Institution: Massachusetts Institute of Technology

Language: English

Topic: Synthesis of Indole Derivatives

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Award: Pericyclic Reactions for Organic Synthesis