Regioselective Iridium-Catalyzed C8-H Borylation of 4-Quinolones via Transient O-Borylated Quinolines

The quinolone-quinoline tautomerization is harnessed to effect the regioselective C8-borylation of biologically important 4-quinolones by using [Ir(OMe)(cod)](2) as the catalyst precursor, the silica-supported monodentate phosphine Si-SMAP as the ligand, and B(2)pin(2) as the boron source. Initially, O-borylation of the quinoline tautomer takes place. Critically, the newly formed 4-(pinBO)-quinolines then undergo N-directed selective Ir-catalyzed borylation at C8. Hydrolysis of the OBpin moiety on workup returns the system to the quinolone tautomer. The C8-borylated quinolines were converted to their corresponding potassium trifluoroborate (BF3K) salts and to their C8-chlorinated quinolone derivatives. The two-step C-H borylation-chlorination reaction sequence resulted in various C8-Cl quinolones in good yields. Conversion to C8-OH-, C8-NH2-, and C8-Ar-substituted quinolones was also feasible by using this methodology.