Heterocycle-Mediated ortho-Functionalization of Aromatic Compounds: The DoM Methodology and Synthetic Utility

Abstract

The directed ortho-lithiation of substituted aromatics containing a small-ring heterocycle as a directing metalating group is described. The reaction of the ortho-lithiated intermediates with electrophiles gives successfully the corresponding substituted derivatives. This brief review highlights the importance of heterocyclic systems as directed metalation groups (DMG) in the regioselective lithiation of simple aromatic compounds. The utility of the synthetic elaboration of the heterocyclic moiety is also stressed. It is possible to access interesting molecules by combining DoM methodology with Negishi or Suzuki–Miyaura cross-coupling protocols.

1 Introduction

2 Lithiation of Aryl-Substituted O-Heterocycles

3 Lithiation of Aryl-Substituted N-Heterocycles

4 Lithiation of Five-Membered Arylheterocycles

5 Conclusion

Key words

arenes - cross-coupling - heterocycles - lithiation - regioselectivity

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