Direct Lactamization of <i>β</i>‐Arylated <i>δ</i>‐Aminopentanoic Acid Carboxamides: En Route to 4‐aryl‐2‐Piperidones, Piperidines, Antituberculosis Molecule Q203 (Telacebec) and its Analogues

Abstract We report the synthesis of 4‐aryl‐2‐piperidone, 4‐arylpiperidine motifs, antituberculosis molecule Q203 (Telacebec) and its analogues. Direct lactamization β ‐C−H arylated N ‐phthaloyl δ ‐aminopentanoic acid carboxamides yielded 4‐aryl‐2‐piperidone (4‐aryl‐ ‐valerolactam) scaffolds. The required were assembled via Pd(II)‐catalyzed, 8‐aminoquinoline‐aided, sp 3 activation arylation method. containing both 8‐aminoquinoline protecting groups directly underwent hydrazine‐mediated to afford 4‐aryl‐2‐piperidones. 4‐Aryl‐2‐piperidone scaffolds then converted into ‐functionalized 4‐aryl‐2‐piperidones, 4‐arylpiperidines, which are structurally closer bio‐active 4‐aryl‐ 2‐piperidone piperidine motifs. A synthetic route for assembling analogues from corresponding 4‐aryl‐2‐piperidones was also shown.