Brønsted acid catalyzed [4 + 2] cycloaddition for the synthesis of bisbenzannulated spiroketals with antifungal activities

Abstract

The intermolecular [4 + 2] cycloaddition of o-hydroxy benzyl alcohols with isochroman ketals was realized by CF₃CO₂H catalysis. A broad range of bisbenzannulated [6,6]-spiroketals were formed under the metal-free mild conditions in moderate to excellent yields (45–98%) with mostly excellent diastereoselectivities (up to >20 : 1 dr). Furthermore, the enantioselective version was also preliminarily investigated and the bisbenzannulated [6,6]-spiroketal was obtained with 61% ee in the presence of Sc(OTf)₃/Feng's chiral N,N′-dioxide ligand. Some of the bisbenzannulated [6,6]-spiroketal products showed good in vitro antifungal activities against Sclerotinia sclerotiorum and Rhizoctonia solani.