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Stereodivergent Synthesis of Enantioenriched 2,3-Disubstituted Dihydrobenzofurans via a One-Pot C–H Functionalization/Oxa-Michael Addition Cascade

Dong‐Xing Zhu, Jianguo Liu, Ming‐Hua Xu

2021Journal of the American Chemical Society122 citationsDOI

Abstract

A one-pot rhodium-catalyzed C-H functionalization/organocatalyzed oxa-Michael addition cascade reaction has been developed. This methodology enables the stereodivergent synthesis of diverse 2,3-disubstituted dihydrobenzofurans with broad functional group compatibility in good yields with high levels of stereoselectivity under exceptionally mild conditions. The full complement of stereoisomers of chiral 2,3-disubstituted dihydrobenzofurans and 3,4-disubstituted isochromans could be accessed at will by appropriate permutations of the two chiral catalysts. The current work provides a rare example of two chiral catalysts independently controlling two contiguous stereogenic centers subsequently via a two-step reaction in a single operation.

Topics & Concepts

StereocenterChemistryStereoselectivitySurface modificationCascadeCatalysisCombinatorial chemistryMichael reactionRhodiumStereochemistryEnantioselective synthesisOrganic chemistryPhysical chemistryChromatographyCatalytic C–H Functionalization MethodsCyclopropane Reaction MechanismsSynthesis and Catalytic Reactions
Stereodivergent Synthesis of Enantioenriched 2,3-Disubstituted Dihydrobenzofurans via a One-Pot C–H Functionalization/Oxa-Michael Addition Cascade | Litcius