Asymmetric Synthesis of 3-Substituted Hexahydro-3H-isochromenes via an Organocatalytic Triple Cascade/Yb-Catalyzed Hetero-Diels–Alder Sequence

Abstract

An efficient two-step asymmetric synthesis of highly substituted 3-alkoxy-hexahydro-3H-isochromenes and 3-sulfenylated hexahydro-3H-isochromenes is described. The procedure involves an organocatalytic triple cascade reaction, followed by an intermolecular [Yb(fod)₃]-catalyzed inverse-electron-demand hetero-Diels–Alder reaction. Using this strategy, a total of six stereogenic centers are obtained with excellent diastereoselectivities and virtually complete enantioselectivities (>95:5 dr, >99% ee).

Key words

asymmetric synthesis - organocatalysis - Diels–Alder reaction - domino reaction - isochromenes

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