Regioselective Synthesis of Benzannulated [5,6]-Oxaspirolactones via Cu(II)-Catalyzed Cycloisomerization of 2-(5-Hydroxyalkynyl)benzoates.

ABSTRACT

Spiroketals and oxaspirolactones are widely found in biologically active natural products, serving as important structural motifs. In this study, we present a Cu(II)-catalyzed cascade cycloisomerization of 2-(5-hydroxyalkynyl)benzoates, enabling the regioselective synthesis of benzannulated [5,6]-oxaspirolactones containing an isochromen-1-one moiety. This strategy offers a rapid and efficient approach to access a diverse array of benzannulated [5,6]-oxaspirolactones. The methodology presented here showcases a broad substrate scope, delivering good yields and scalability up to gram scale. The structures of the oxaspirolactones were unequivocally confirmed through single-crystal X-ray analysis and by analogy using 1H and 13C{1H} NMR data.