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

• Published in: Chemistry : a European journal Vol. 29; no. 48; pp. e202301734 - n/a
• Main Authors: Al Mamari, Hamad H., Borel, Julie, Hickey, Aobha, Courtney, Eimear, Merz, Julia, Zhang, Xiaolei, Friedrich, Alexandra, Marder, Todd B., McGlacken, Gerard P.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.08.2023; Wiley Subscription Services, Inc
• Subjects: Bioactive; Boron; boronate ester; boronic acid; Catalysts; Chemistry; Chemistry, Multidisciplinary; C−H activation; Iridium; Organic compounds; Phosphine; Phosphines; Physical Sciences; Potassium; Quinoline; Quinolines; Quinolones; Regioselectivity; Science & Technology; Silica; Silicon; tautomer; Tautomers; C(SP)-H BONDS; boronic acid; ARENES; HYDROSILYLATION; QUINOLONES; COMPLEXES; BOND FUNCTIONALIZATION; Bioactive; C-H activation; HETEROCYCLES; tautomer; boronate ester; SITE-SELECTIVITY; C(SP)-H; C−H activation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202301734

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 B2pin2 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. The quinolone–quinoline tautomerization allows the regioselective C8‐borylation of biologically important 4‐quinolones by using [Ir(OMe)(cod)]2 as catalyst precursor, Si‐SMAP as the ligand, and B2pin2 as boron source. Following O‐borylation of the quinoline tautomer, N‐directed selective Ir‐catalyzed borylation takes place at C8. Hydrolysis of the OBpin moiety on workup returns the system to the quinolone tautomer.