Palladium-Catalyzed Regioselective Alkynylation of Pyrroles and Azoles under Mild Conditions: Application to the Synthesis of a Dopamine D-4 Receptor Agonist

Etienne Brachet; Philippe Belmont

doi:10.1021/acs.joc.5b01093

Palladium-Catalyzed Regioselective Alkynylation of Pyrroles and Azoles under Mild Conditions: Application to the Synthesis of a Dopamine D-4 Receptor Agonist

J Org Chem. 2015 Aug 7;80(15):7519-29. doi: 10.1021/acs.joc.5b01093. Epub 2015 Jul 24.

Authors

Etienne Brachet^{1

2}, Philippe Belmont^{1

2}

Affiliations

¹ †Université Paris Descartes, Faculté de Pharmacie de Paris, UMR CNRS 8638 (COMETE), 4 avenue de l'Observatoire, Paris FR-75006, France.
² ‡Université Sorbonne Paris Cité (USPC), 12 rue de l'école de Médecine, Paris FR-75006, France.

PMID: 26176588
DOI: 10.1021/acs.joc.5b01093

Abstract

A mild and general method for the direct alkynylation of azoles such as pyrrole, indole, and 7-azaindole is described here. Using a simple catalytic system such as Pd(OAc)2 (2.5 mol %), P(tBu)2Me·HBF4 (5 mol %), and NaOAc (2 equiv) allowed the regioselective introduction of various alkynyl residues at the C-2 position of pyrroles. Interestingly, C-2 alkynylation was also observed on C-3-substituted indoles, whereas classical C-3 alkynylation was obtained on selected unsubstituted indoles and 7-azaindole. Our methodology has been illustrated by the efficient synthesis of a potential schizophrenia drug (dopamine D-4 inhibitor).