title: Palladium-Catalyzed Regioselective Alkynylation of Pyrroles and Azoles under Mild Conditions: Application to the Synthesis of a Dopamine D-4 Receptor Agonist.
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).
authors.affiliation: †Université Paris Descartes, Faculté de Pharmacie de Paris, UMR CNRS 8638 (COMETE), 4 avenue de l'Observatoire, Paris FR-75006, France.|‡Université Sorbonne Paris Cité (USPC), 12 rue de l'école de Médecine, Paris FR-75006, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Brachet
authors.affiliation: †Université Paris Descartes, Faculté de Pharmacie de Paris, UMR CNRS 8638 (COMETE), 4 avenue de l'Observatoire, Paris FR-75006, France.|‡Université Sorbonne Paris Cité (USPC), 12 rue de l'école de Médecine, Paris FR-75006, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Belmont