Palladium-Catalyzed Miyaura Borylation of Overly Crowded Aryl Chlorides Enabled by a Complementary Localized/Remote Steric Bulk of Ligand Chassis

Unlike
common cross-coupling reaction examples using privileged
substrates, the coupling processes employing highly sterically congested
electrophilic partners have been a lasting challenge. Here, we report
a general Pd-catalyzed Miyaura borylation of sterically hindered aryl
chlorides. The key to the success of this reaction is the distinctive
tailor-made phosphine ligand that features a smaller phosphine head
and a larger remote steric bulk. This concept is, on the contrary,
complementary to the existing characteristics of common phosphines,
e.g., Pt-Bu3, biaryl-PCy2,
etc., where they consist of a localized steric bulk at the phosphorous
center. In fact, the smaller phosphine motif effectively allows the
coupling partner to approach the Pd center at the initial stage. Our
finding showed that even an extremely sterically hindered 2,6-di-iso-propyl-substituted aryl chloride was applicable under
this developed catalyst system. Nice functional group compatibility
was observed under these reaction conditions and the catalyst loading
down to 0.05 mol % Pd could be achieved for a particular entry. The
success of this ligand-enabled C–B bond formation is believed
to offer unique fundamental knowledge for attaining catalyst establishments
fit for other highly sterically hindered cross-coupling reactions
of relevance.