Enantiospecific Synthesis of ortho-Substituted Benzylic Boronic Esters by a 1,2-Metalate Rearrangement/1,3-Borotropic Shift Sequence

High Resolution Image Download MS PowerPoint Slide Coupling reactions between benzylamines and boronic esters have been investigated. ortho -Lithiated benzylamines react with boronic esters and a N -activator to afford ortho -substituted benzylic boronic esters with formal 1,1′-benzylidene insertion into the C–B bond. The reaction occurs by a S N 2′ elimination and 1,2-metalate rearrangement of the N -activated boronate complex to afford a dearomatized intermediate, which undergoes a Lewis-acid catalyzed 1,3-borotropic shift to afford the boronic ester products in high yield and with excellent enantiospecificity. The use of enantioenriched α-substituted benzylamines gave the corresponding secondary boronic esters with high ee.