Pd-Catalyzed Synthesis of Indeno[1,2-c]chromenes from 2-Alkynylhalobenzenes

Key words

indeno[1,2-c]chromenes - 2-alkynylbromobenzenes - 2-(2-phenylethynyl)phenols - palladium catalysis

Significance

Reported is the synthesis of ­indeno[1,2-c]chromenes 3 and 4 via a palladium-catalyzed reaction of 2-alkynylbromobenzenes 1 with either 2-(2-arylethynyl)phenols 2 or with water. A range of ligands was used during the optimization study to reveal that the reaction proceeds only with Cy₃P as ligand (eq. 1). Sodium methoxide in toluene or 1,4-dioxane was better than other combinations. The substrate scope of this transformation was modestly demonstrated. The reaction also proceeded to give 3 in 78% yield by treatment of 1-chloro-2-(2-phenylethynyl)benzene with 2 (R³ = H, R⁴ = Ph). Surprisingly, re-optimization was required in the reaction of 1 with water (eq. 2). Both alkyl- and aryl-substituted alkynes were tolerated under the optimized conditions. However, the reaction parameters had to be re-screened to give a satisfactory yield of compounds with ­electron-withdrawing groups (R² = 4-ClC₆H₄, 4-AcC₆H₄).

Comment

The [6.5.6.6]-tetracyclic core of indenochromenes 3 and 4 is present in several bioactive compounds (B. S. Min et al. Bioorg. Med. Chem. Lett. 2012, 22, 7436). Very few synthetic methods such as iron-mediated [3+2]-annulation reactions are available to provide access to this tetracyclic system (Z.-Q. Wang et al. Org. Lett. 2011, 13, 14). The present method provides a rapid construction of various substituted indenochromenes from easily accessible starting materials. One drawback of this method is the lower yield for electron-poor substrates. Although, this work provides a facile synthesis of indeno[1,2-c]-chromenes, it is strikingly similar to the authors’ previous work (Y. Luo, L. Hong, J. Wu Chem. Commun. 2011, 47, 5298) .