Chiral Phosphoric Acid Catalyzed Desymmetrization of Cyclopentendiones via Friedel–Crafts Conjugate Addition of Indolizines
Qijian Ni, Zhiming Zhu, Yanjun Fan, Xiaoyun Chen, Xiaoxiao Song
Abstract
An organocatalytic highly diastero- and enantioselective Friedel–Crafts conjugate addition of indolizines to prochiral cyclopentenediones has been successfully developed. This desymmetric transformation provides a direct access to the desired indolizine-substituted cyclopentanediones in yields of 62–91% and excellent stereoselectivities. The utility of the approach was demonstrated by diverse late-stage functionalizations through reduction or oxidation. Importantly, the direct sp2 C–H functionalization with nitromethane in one-pot process resulted in the indolizine-linked axially chiral styrene bearing a remote chiral center.
Topics & Concepts
IndolizineChemistryNitromethaneEnantioselective synthesisPhosphoric acidConjugateFriedel–Crafts reactionDesymmetrizationCatalysisCombinatorial chemistryOrganocatalysisOrganic chemistryBrønsted–Lowry acid–base theoryMathematical analysisMathematicsSynthesis and Reactivity of HeterocyclesCyclopropane Reaction MechanismsCatalytic C–H Functionalization Methods