Synthesis 2016; 48(13): 1993-2008
DOI: 10.1055/s-0035-1561596
short review
© Georg Thieme Verlag Stuttgart · New York

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

Saverio Florio*
a  CINMPIS Consortium, Dipartimento di Farmacia-Scienze del Farmaco, Università di Bari, Via E. Orabona 4, 70125 Bari, Italy   Email: [email protected]
,
Antonio Salomone
a  CINMPIS Consortium, Dipartimento di Farmacia-Scienze del Farmaco, Università di Bari, Via E. Orabona 4, 70125 Bari, Italy   Email: [email protected]
b  Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, Università del Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy
› Author Affiliations
Further Information

Publication History

Received: 13 February 2016

Accepted after revision: 04 March 2016

Publication Date:
26 April 2016 (online)


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

 
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