Stereospecific Cross Couplings To Set Benzylic, All-Carbon Quaternary Stereocenters in High Enantiopurity

Asymmetric
preparation of all-carbon quaternary stereocenters is
an important goal. Despite advances in formation of highly enantioenriched
products with quaternary stereocenters proximal to a functional group,
methods to install quaternary stereocenters isolated from functional
groups are limited. Transition metal catalysis offers a potential
solution, but prior cross couplings are limited to allylic substrates
or deliver little to no enantiomeric enrichment. We report a stereospecific,
nickel-catalyzed Suzuki–Miyaura arylation of tertiary benzylic
acetates to deliver products with diaryl and triaryl quaternary stereocenters
in high yields and ee’s. This reaction employs an inexpensive,
air-stable Ni­(II) salt and commercially available phosphine ligand
to transform tertiary alcohol derivatives, which are easily available
in exceptional ee, into valuable products with stereoretention.