What question did this study set out to answer?

The aim is to achieve rapid and selective metalation of pyridines at room temperature using mixed Ti-TMP and Ti-Fe-TMP amides.

April 12, 2026

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

We have developed two mixed-metal TMP amides (TMP = 2,2,6,6-tetramethylpiperidyl), Ti-1·2(TMPMgCl·LiCl) and Ti-1·FeCl2·2(TMPMgCl·LiCl), to enable the rapid metalation of various unactivated and functionalized pyridines with high functional group tolerance and regioselectivity at room temperature. These novel organometallic reagents demonstrate unprecedented regiodivergence: Ti-1·2(TMPMgCl·LiCl) selectively metalates 2- or 3-functionalized pyridines at the C6 position, while Ti-1·FeCl2·2(TMPMgCl·LiCl) promotes the metalations ortho to the functional groups.

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Cite This Study

Ma et al. (Thu,) studied this question.

synapsesocial.com/papers/69db36e64fe01fead37c4e0e https://doi.org/https://doi.org/10.1021/acs.orglett.6c01169

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