Gold(I)-Catalyzed Intramolecular SEAr Reaction: Efficient Synthesis of Isoxazole-Containing Fused Heterocycles.

Abstract

Intramolecular electrophilic aromatic substitution (SEAr) reaction at the 5-position of isoxazoles was achieved. The electron-donating heteroatoms (N and O) at the 4-position of isoxazoles, which can be readily prepared based on our originally developed synthetic procedure, and a cationic gold(I) catalyst are essential for the intramolecular SEAr reaction to synthesize isoxazole-containing fused heterocycles. Structurally diverse isoxazolopyridines 6 and isoxazolopyrans 9, including base-labile 3-unsubstituted derivatives, were synthesized in good to high yields. The addition of N-phenylbenzaldimine as a hydrogen acceptor improved yields in the synthesis of isoxazolopyridines. Furthermore, synthesis of the tetracyclic fused ring system 12 was achieved by tandem cyclization from the corresponding diyne 11.