Iridium-Catalyzed Borylation of 6-Fluoroquinolines: Access to 6-Fluoroquinolones

Abstract

The Ir-catalyzed C–H borylation of fluoroquinolines has been realized. The quinoline boronic ester formed undergoes a range of important transformations of relevance to medicinal chemistry. Judicious choice of the substituent at C4 on the quinoline facilitated the unmasking of a fluoroquinolone—the core structure of many antibiotics.

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

“…We thus report herein a C8‐site‐selective directed Ir‐catalyzed C−H borylation of 4‐quinolones, which were further functionalized to provide access to C8‐chlorinated quinolones of potential biological importance (Scheme 2). This C8 functionalization protocol complements our recently reported C7 site‐selective Ir/dtbpy catalyzed borylation of 6‐fluoroquinolines [28a] . However, herein we harness the transient quinoline tautomer to direct C−H activation at C8.…”

“…The Ir‐catalyzed C−H borylation is largely driven by steric effects (Scheme 1 vii), although electronic effects may also assist in this selectivity possibly, in this case, by the ortho ‐directing ability of fluorine [28b,c] . The resulting C7‐borylated 6‐fluoroquinolines were further elaborated into their C7‐functionalized counterparts, ultimately providing access to C7‐functionalized 6‐fluoroquinolones [28a] . In this case, direct functionalization of 4‐quinolones was not possible under the conditions employed.…”

“…In a recent report, Marder, McGlacken, and co‐workers demonstrated the site‐selective Ir‐catalyzed C−H borylation of 6‐fluoroquinolines using dtbpy as the ligand (Scheme 1 vii) [28a] . The Ir‐catalyzed C−H borylation is largely driven by steric effects (Scheme 1 vii), although electronic effects may also assist in this selectivity possibly, in this case, by the ortho ‐directing ability of fluorine [28b,c] .…”