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

We report the synthesis of 4‐aryl‐2‐piperidone, 4‐arylpiperidine motifs, antituberculosis molecule Q203 (Telacebec) and its analogues. Direct lactamization of β‐C−H arylated N‐phthaloyl δ‐aminopentanoic acid carboxamides yielded 4‐aryl‐2‐piperidone (4‐aryl‐δ‐valerolactam) scaffolds. The required β‐C−H arylated N‐phthaloyl δ‐aminopentanoic acid carboxamides were assembled via the Pd(II)‐catalyzed, 8‐aminoquinoline‐aided, sp3β‐C−H activation and arylation method. The β‐C−H arylated N‐phthaloyl δ‐aminopentanoic acid carboxamides containing both 8‐aminoquinoline and N‐phthaloyl protecting groups directly underwent the hydrazine‐mediated lactamization to afford 4‐aryl‐2‐piperidones. 4‐Aryl‐2‐piperidone scaffolds were then converted into N‐functionalized 4‐aryl‐2‐piperidones, 4‐arylpiperidines, which are structurally closer to bio‐active 4‐aryl‐ 2‐piperidone and piperidine motifs. A synthetic route for assembling antituberculosis molecule Q203 and its analogues from the corresponding 4‐aryl‐2‐piperidones was also shown. [ABSTRACT FROM AUTHOR]