Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes

A tertiary
stereogenic center that bears two different aryl substituents
is found in a variety of bioactive compounds, including medicines
such as Zoloft and Detrol. We have developed an efficient method for
the synthesis of enantioenriched 1,1-diarylalkanes from readily available
racemic benzylic alcohols. Formation of a benzylic mesylate (which
is not isolated), followed by treatment with an arylzinc reagent,
LiI, and a chiral nickel/bis­(oxazoline) catalyst, furnishes the Negishi
cross-coupling product in high ee and good yield. A wide array of
functional groups (e.g., an aryl iodide, a thiophene, and an N-Boc-indole) are compatible with the mild reaction conditions.
This method has been applied to a gram-scale synthesis of a precursor
to Zoloft.