Construction of Benzylic Stereogenic Carbon Centers through Enantioselective Arylation Reactions

Compounds bearing chiral benzylic stereocenters are important and frequently occur in natural products and drug molecules. In this account, we discuss our recent results on the construction of ­benzylic stereogenic centers based on enantioselective arylation and related domino sequences, mainly including asymmetric Friedel–Crafts alkylation reactions and asymmetric Heck reactions.1 Introduction2 The Catalytic Asymmetric Friedel–Crafts Alkylation Reaction2.1 Reactions of Electron-Deficient Alkenes2.2 Reactions of Active Ketimines2.3 Reactions of Nitrones2.4 Reactions of Aziridines3 The Asymmetric Heck Reaction3.1 Dearomative Heck Reactions and Related Domino Sequences3.2 Heck Reactions of in situ Formed Enamines4 Conclusion and Outlook

Access to enantioenriched 2,3- and 2,5-dihydrofurans with a fully substituted C2 stereocenter by Pd-catalyzed asymmetric intermolecular Heck reaction

A palladium catalyzed intermolecular asymmetric Heck reaction provides access to valuable 2,3- and 2,5-dihydrofurans with a fully substituted C2 stereocenter with high levels of regio- and enantiocontrol.

Kinetic resolution of 2-substituted-2,3-dihydrofurans by a palladium-catalyzed asymmetric Heck reaction

The kinetic resolution of 2-substituted-dihydrofurans via a Pd-catalyzed asymmetric Heck reaction was realized for the first time.

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

A novel class of chiral phosphanyl-oxazoline (PHOX) ligands with a conformationally rigid cyclopropyl backbone was synthesized and tested in the intermolecular asymmetric Heck reaction. Mechanistic modelling and crystallographic studies were used to predict the optimal ligand structure and helped to design a very efficient and highly selective catalytic system. Employment of the optimized ligands in the asymmetric arylation of cyclic olefins allowed for achieving high enantioselectivities and significantly suppressing product isomerization. Factors affecting the selectivity and the rate of the isomerization were identified. It was shown that the nature of this isomerization is different from that demonstrated previously using chiral diphosphine ligands.