Ir/Brønsted acid dual-catalyzed asymmetric synthesis of bisbenzannulated spiroketals and spiroaminals from isochroman ketals

Abstract

Herein, we reported an Ir/Brønsted acid dual-catalyzed asymmetric cascade reaction of 2-(1-hydroxyallyl)-phenols with isochroman ketals to produce bisbenzannulated spiroketals in high efficiency with generally high diastereo- and enantioselectivities (up to 17 : 1 dr, >99% ee). The procedure involved the generation of exocyclic enol ethers from isochroman ketals through Brønsted acid catalysis, followed by an Ir-catalyzed enantioselective allylation/spiroketalization sequence with 2-(1-hydroxyallyl)-phenols. Mechanistic investigations and theoretical calculations revealed that chiral iridium catalyst controlled the enantioselectivity, while the high diastereoselectivity was attributed to a Brønsted acid-promoted thermodynamically controlled epimerization process. Furthermore, the asymmetric cascade reaction involving 2-(1-hydroxyallyl)anilines was found to be applicable for synthesizing optically pure bisbenzannulated spiroaminals. Additionally, some of the bisbenzannulated spiroketal products showed promising inhibitory activity against Rhizoctonia solani, suggesting their potential applications in agrochemical discovery.