Organocatalytic Asymmetric Synthesis of Cyclic Acetals with Spirooxindole Skeleton

Abstract

An organocatalytic asymmetric synthesis of cyclic acetal with spirooxindole skeleton has been developed via a domino reaction between isatin and γ-hydroxy enones. Bifunctional squaramide catalyst with adamantyl motif was found to be the most effective for the cascade reaction. With 10 mol% of the catalyst, the desired products were obtained in 1.8:1 to 9:1 diastereo-and 86% to > 99% enantioselectivities from a range of substituted isatins and γ-hydroxy enones.

Expeditious entry into carbocyclic and heterocyclic spirooxindoles

“…A chiral squaramide derived from bifunctional cinchona alkaloid possessing a definite C 22 moiety has effectively catalyzed one-pot sequential reactions between isatin 5 and γ-hydroxy enones 180 (Scheme 105). 79 The resulting cyclic acetal with a spirooxindole skeleton was formed in moderate to excellent yields, diastereoselectivities, and enantioselectivities up to >99%. An electron-withdrawing substituent at the 7 th position of isatin gave moderate yields.…”

Recent advances in the asymmetric catalytic construction of oxa-quaternary carbon centers

“…In 2021, Pan and coworkers developed an organocatalytic asymmetric synthesis of cyclic acetal with a spirooxindole skeleton, which proceeded via a domino reaction between isatins and γ-hydroxy enones. 57 A bifunctional squaramide catalyst with an adamantyl motif was found to be the most effective for the cascade reaction. With 10 mol% of the catalyst, the desired products were obtained with good diastereoselectivities with high enantioselectivities from a series of substituted isatins and γ-hydroxy enones (Scheme 42).…”