N-acylphthalimides: Efficient acyl coupling reagents in suzuki-miyaura cross-coupling by N-C cleavage catalyzed by Pd-PEPPSI precatalysts

Abstract

We report a general, highly selective method for Suzuki-Miyaura cross-coupling of N-acylphthalimides via N-C(O) acyl cleavage catalyzed by Pd-PEPPSI-type precatalysts. Of broad synthetic interest, the method introduces N-acylphthalimides as new, bench-stable, highly reactive, twist-controlled, amide-based precursors to acyl-metal intermediates. The reaction delivers functionalized biaryl ketones by acylative Suzuki-Miyaura cross-coupling with readily available boronic acids. Studies demonstrate that cheap, easily prepared, and broadly applicable Pd-PEPPSI-type precatalysts supported by a sterically demanding IPr (1,3-Bis-(2,6-diisopropylphenyl)imidazol-2-ylidene) ancillary ligand provide high yields in this reaction. Preliminary selectivity studies and the effect of Pd-N-heterocyclic carbenes (NHC) complexes with allyl-type throw-away ligands are described. We expect that N-acylphthalimides will find significant use as amide-based acyl coupling reagents and cross-coupling precursors to acyl-metal intermediates.