A valuable Lewis-acid-catalysed domino reaction involving a Friedel–Crafts alkylation of variously substituted phenols followed by a direct lactonization has been successfully developed (22 examples, yields up to 98%). This protocol tolerates not only opposite electron demand substituents on the starting materials, but also drastic modifications of the alkylating agents, and gives direct access to the corresponding 3-hydroxy-benzofuran-2-ones, which could easily undergo further chemical transformation. The relevance of our method was further confirmed by the straightforward synthesis of rac-BHFF, the recently discovered and extremely promising positive allosteric modulator of the GABAB receptor.
A valuable Lewis-acid-catalysed domino reaction involving a Friedel-Crafts alkylation of variously substituted phenols followed by a direct lactonization has been successfully developed (22 examples, yields up to 98%). This protocol tolerates not only opposite electron demand substituents on the starting materials, but also drastic modifications of the alkylating agents, and gives direct access to the corresponding 3-hydroxy-benzofuran-2-ones, which could easily undergo further chemical transformation. The relevance of our method was further confirmed by the straightforward synthesis of rac-BHFF, the recently discovered and extremely promising positive allosteric modulator of the GABA(B) receptor.
Catalytic Friedel-Crafts/Lactonization Domino Reaction: Facile Access to 3-Hydroxybenzofuran-2-one Scaffold / Vetica, Fabrizio; Alessandra, Pelosi; Gambacorta, Augusto; Loreto, Maria Antonietta; Antonietta Loreto, M.; Miceli, Martina; Gasperi, Tecla. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - STAMPA. - 2014:9(2014), pp. 1899-1906. [10.1002/ejoc.201301686]
Catalytic Friedel-Crafts/Lactonization Domino Reaction: Facile Access to 3-Hydroxybenzofuran-2-one Scaffold
Fabrizio Vetica;GAMBACORTA, Augusto;LORETO, Maria Antonietta;MICELI, MARTINA;GASPERI, TECLA
2014
Abstract
A valuable Lewis-acid-catalysed domino reaction involving a Friedel–Crafts alkylation of variously substituted phenols followed by a direct lactonization has been successfully developed (22 examples, yields up to 98%). This protocol tolerates not only opposite electron demand substituents on the starting materials, but also drastic modifications of the alkylating agents, and gives direct access to the corresponding 3-hydroxy-benzofuran-2-ones, which could easily undergo further chemical transformation. The relevance of our method was further confirmed by the straightforward synthesis of rac-BHFF, the recently discovered and extremely promising positive allosteric modulator of the GABAB receptor.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
