Ruthenium-Catalyzed Heteroannulation Route to Benzofurans and Isochromenes

Significance

Reported is a ruthenium-catalyzed cycloisomerization of aromatic alkynols 1, 3, 5 and 7 to afford isochromenes 2 and benzofurans 6. The combination of CpRuCl(PPh₃)₂ and amine (crucial for the catalytic cycle) promotes the chemo- and regioselective cycloisomerization (6- and 5-endo cyclization). Both electron-rich and electron-poor substrates 1 and 5 give good yields of the corresponding isochromenes and benzofurans. However, while smooth 6-endo cyclization occurred with secondary and tertiary benzylic alcohol 1, 2-ethynylbenzoic acid 3 underwent only 5-exo cyclization to afford benzofuran 4. In an intelligent experiment with compound 7, the 5-endo regioselectivity of the cyclization to exclusively benzofuran 8 was demonstrated.