Dynamic Kinetic Asymmetric Heck Reaction for the Simultaneous Generation of Central and Axial Chirality

A highly diastereo-
and enantioselective, scalable Pd-catalyzed
dynamic kinetic asymmetric Heck reaction of heterobiaryl sulfonates
with electron-rich olefins is described. The coupling of 2,3-dihydrofuran
or N-boc protected 2,3-dihydropyrrole with a variety of quinoline,
quinazoline, phthalazine, and picoline derivatives takes place with
simultaneous installation of central and axial chirality, reaching
excellent diastereo- and enantiomeric excesses when in situ formed
[Pd0/DM-BINAP] was used as the catalyst, with loadings
reduced down to 2 mol % in large scale reactions. The coupling of
acyclic, electron-rich alkenes can also be performed using a [Pd0/Josiphos ligand] to obtain axially chiral heterobiaryl α-substituted
alkenes in high yields and enantioselectivities. Products from Boc-protected
2,3-dihydropyrrole can be easily transformed into N,N ligands or appealing axially chiral, bifunctional
proline-type organocatalysts. Computational studies suggest that a
β-hydride elimination is the stereocontrolling step, in agreement
with the observed stereochemical outcome of the reaction.