Regiodivergent Metalation of Pyridines Using Mixed Ti-TMP and Ti–Fe-TMP Amides at Room Temperature

Key Points

• The aim is to achieve rapid and selective metalation of pyridines at room temperature using mixed Ti-TMP and Ti-Fe-TMP amides.
• Developed two novel mixed-metal TMP amides: Ti-1·2(TMPMgCl·LiCl) and Ti-1·FeCl2·2(TMPMgCl·LiCl)
• Evaluated their ability to metalate various unactivated and functionalized pyridines
• Assessed regioselectivity and functional group tolerance at room temperature
• Ti-1·2(TMPMgCl·LiCl) selectively metalates at the C6 position of 2- or 3-functionalized pyridines
• Ti-1·FeCl2·2(TMPMgCl·LiCl) promotes metalation ortho to functional groups
• Demonstrated unprecedented regiodivergent behavior in metalation reactions

Abstract