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.