Enantiospecific, Regioselective Suzuki-Miyaura Cross-Couplings of Secondary, Allylic Boronic Esters

Abstract

The stereochemical course of the Pd–catalyzed Suzuki-Miyaura cross-coupling of α-substituted, enantioenriched allylic boronic esters with phenyl iodide has been examined. The secondary boronic esters were prepared in both racemic and enantioenriched forms via borylationof a lithiated carbenoid with a geometrically defined vinyl boronic ester. The geometric purities were determined to be >99% and the enantiomeric excesses of stereodefined secondary boronic esters were found to exceed 98:2. In total, 8 allylic boronic esters were successfully cross-coupled, providing arylated products with high regioselectivities (>90:10) and complete enantiospecificities (>99%). The cross-coupling of a sterically and electronically unbiased, deuterated substrate confirmed that fully equilibrated π-allylic intermediates are not involved. Additionally, correlating the absolute configurations of the allylic boronic ester and the cross-coupling product allowed us to confirm that the transmetalation step of the reaction proceeded through a closed transition state via a syn-SE’ mechanism, which further suggests the importance of the distinct Pd-O-B bond linkage. Further, the cross-coupling of vinyl iodides to secondary boronic esters was investigated.