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Tetrasubstituted Carbon Stereocenters via Copper-Catalyzed Asymmetric Sonogashira Coupling Reactions with Cyclic gem-Dihaloketones and Tertiary α-Carbonyl Bromides

Xueling Mo, Han Cheng Huang, Guozhu Zhang

2022ACS Catalysis43 citationsDOI

Abstract

The construction of chiral tetrasubstituted carbon stereocenters is an ongoing challenge in synthetic organic chemistry due to its prevalence in multiple disciplines. One efficient approach is the catalytic asymmetric C–C coupling reactions of a readily available racemic tertiary alkyl electrophile by simple organic nucleophiles. While a variety of secondary alkyl halides succeeded in asymmetric Cu-catalyzed Sonogashira-type cross-coupling reactions with diverse alkynes, tertiary alkyl halides have rarely been used in this kind of coupling reaction. Herein, we demonstrate that tertiary bromides can serve as efficient coupling partners in copper/bisoxazoline phenyl amine (BOPA)-catalyzed asymmetric alkynylation, leading to synthetically and medicinally valuable tertiary C–F stereocenters and all-carbon quaternary stereocenters.

Topics & Concepts

StereocenterSonogashira couplingChemistryAlkylNucleophileElectrophileCatalysisTertiary amineEnantioselective synthesisCombinatorial chemistryOrganic chemistryCoupling reactionMedicinal chemistryPalladiumFluorine in Organic ChemistryCatalytic C–H Functionalization MethodsAsymmetric Synthesis and Catalysis