A Practical, One-Pot Synthesis of Highly Substituted Thiophenes and Benzo[b]thiophenes from Bromoenynes and o-Alkynylbromobenzenes

An efficient synthesis of thiophenes and benzo[b]thiophenes has been developed from easily available bromoenynes and o-alkynylbromobenzene derivatives. This novel one-pot procedure involves a Pd-catalyzed C–S bond formation using a hydrogen sulfide surrogate followed by a heterocyclization reaction. Moreover, in situ functionalization with selected electrophiles further expands the potential of this methodology to the preparation of the corresponding highly substituted sulfur heterocycles.Junta de Castilla y Leon (BU021A09 and GR-172) and Ministerio de Ciencia e Innovacion (MICINN) and FEDER (CTQ2010-15358 and CTQ2009-09949/BQU) for financial support. P.G.-G. and M.A.F.-R. thank MICINN for "Juan de la Cierva" and "Ramon y Cajal" contractsJunta de Castilla y Leon (BU021A09 and GR-172) and Ministerio de Ciencia e Innovacion (MICINN) and FEDER (CTQ2010-15358 and CTQ2009-09949/BQU) for financial support. P.G.-G. and M.A.F.-R. thank MICINN for "Juan de la Cierva" and "Ramon y Cajal" contractsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Letters, copyright © American Chemical Society after peer review and technical editing by the publisher

Synthesis of the ortho/meta/para Isomers of relevant pharmaceutical compounds by coupling a sonogashira reaction with a regioselective hydration

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Catalysis, copyright © American Chemical Society after peer review and technical editing by the publisher.Aryl ketones substituted in ortho, meta, and para position are prepared by a palladium-catalyzed Sonogashira reaction followed by a regioselective hydration of the soformed alkyne with triflimidic acid or a gold catalyst, under catalytic conditions. This methodology opens a way to obtain substituted aryl alkyl ketones from readily available starting materials, haloarenes, and terminal alkynes. The syntheses of the different regioisomers of haloperidol, melperone, pipamperone, and ibuprofen are presented. Structure−activity relationships for these compounds are studied with dopaminergic and cyclooxigenase binding assays.Financial support by the Severo Ochoa program and Consolider-Ingenio 2010 (proyecto MULTICAT) from MCIINN is acknowledged, and also to the King Saud University. A.L.-P. thanks ITQ for a contract. J.R. C.-A. and P.R.M. thank MCIINN for the concession of a FPU contract.Leyva Perez, A.; Cabrero Antonino, JR.; Rubio Marqués, P.; Al-Resayes, SI.; Corma Canós, A. (2014). Synthesis of the ortho/meta/para Isomers of relevant pharmaceutical compounds by coupling a sonogashira reaction with a regioselective hydration. ACS Catalysis. 4(3):722-731. https://doi.org/10.1021/cs401075zS7227314