Publications > Virumbrales et al

Org Biomol Chem. 2018 Apr 18;16(15):2623-2628. doi: 10.1039/c8ob00406d.

Gold(i)-catalyzed diastereoselective synthesis of 1-α-oxybenzyl-1H-indenes.

Cintia Virumbrales^a, Samuel Suárez-Pantiga, Marta Solas, Manuel A Fernández-Rodríguez, Roberto Sanz

Área de Química Orgánica, Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001 Burgos, Spain.

a. rsd@ubu.es

Abstract

The gold(i)-catalyzed oxycyclization of β-aryl monosubstituted o-(alkynyl)styrenes gives rise to 1-α-methoxy or 1-α-hydroxybenzyl-1H-indenes in a diastereospecific way. In contrast to β,β-disubstituted o-(alkynyl)styrenes, the stereochemical outcome of this process, diastereospecific reaction supports the higher contribution of a gold intermediate with a cyclopropylcarbene-like character.

Publications > García-García et al

J Org Chem. 2017 Jan 20;82(2):1155-1165. doi: 10.1021/acs.joc.6b02788.

Synthesis of Functionalized 1H-Indenes and Benzofulvenes through Iodocyclization of o-(Alkynyl)styrenes.

Patricia García-García¹, Ana M Sanjuán², Muhammad A Rashid², Alberto Martínez-Cuezva², Manuel A Fernández-Rodríguez², Félix Rodríguez³, Roberto Sanz²

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá , 28871 Alcalá de Henares, Madrid, Spain.  2. Área de Química Orgánica, Departamento de Química, Facultad de Ciencias, Universidad de Burgos , Pza. Misael Bañuelos s/n, 09001 Burgos, Spain.  3. Instituto Universitario de Química Organometálica "Enrique Moles", Universidad de Oviedo , C/Julián Clavería, 8, 33006 Oviedo, Spain.

Abstract

A convenient method for the preparation of synthetically useful 3-iodoindene derivatives has been developed. This protocol, based on the 5-endo iodocyclization reaction of o-(alkynyl)styrenes, represents one of the scarce examples of halocyclizations using olefins as nucleophilic counterparts and allows the synthesis of both 3-iodo-1H-indenes (from β-alkyl-β-alkyl/aryl-o-(alkynyl)styrenes) and 3-iodobenzofulvenes (from β,β-diaryl-o-(alkynyl)styrenes) in good yields under mild reaction conditions. In addition, related alkoxyiodocyclization processes are described, which are particularly interesting in their intramolecular version because they allow the synthesis of heteropolycyclic structures containing the indene core. Finally, the usefulness of the prepared 3-iodoindenes has been demonstrated by the synthesis of several polysubstituted indene derivatives through conventional palladium-catalyzed cross-coupling reactions and iodine-lithium exchange processes.

Publications > Fernández-García et al

Advanced Synthesis Catalysis. 2017; 359(17):3035-3051. doi: 10.1002/adsc.201700264

Gold-Catalyzed Cycloisomerizations of Functionalyzed Cyclopropyl Alkynes: the Cases of Carboxamides and Alcohols

Jesús M. Fernández-García, Hugo A. Garro, Laura Fernández-García, Patricia García-García, Manuel A. Fernández-Rodríguez, Isabel Merino, Enrique Aguilar

Palabras clave: Alkynes; gold; nucleophilic addition; ring expansion; seven-membered heterocycles; pyranones

Resumen

Push-pull alkynylcyclopropane derivatives are claimed as suitable and active substrates for gold-catalyzed transformations. Thus, 2(3H)-azepinones can be readily prepared from alkynylcyclopropanecarboxamides through a nucleophilic addition/cyclopropane ring-opening cascade process and, in this manuscript, the scope and the limitations of such reaction sequence are reported. The cascade reaction is general and occurs with complete regio- and quimioselection to form the seven-membered heterocycles with the exception of primary alkyl-substituted alkynylcyclopropanecarboxamides that render 4-methoxy-6-oxo-4-enenitriles in moderate yields. Additionally, less activated alkynylcyclopropylmethanols undergo regioselective cycloisomerization at low temperature leading to oxabicyclo%@5B4.1.0%@5Dheptanes. Notably, the cyclopropane ring opening of these adducts takes place under thermal conditions to form dihydropyranones.

Publications > Aguilar et al

Chem Rev. 2016 Jul 27;116(14):8256-311. doi: 10.1021/acs.chemrev.6b00181.

1,3-Dien-5-ynes: Versatile Building Blocks for the Synthesis of Carbo- and Heterocycles.

Enrique Aguilar¹, Roberto Sanz², Manuel A Fernández-Rodríguez², Patricia García-García³

1. Instituto Universitario de Química Organometálica "Enrique Moles", Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo , C/Julián Clavería 8, 33006 Oviedo, Spain.  2. Departamento de Química, Área de Química Orgánica, Facultad de Ciencias, Universidad de Burgos , Pza. Misael Bañuelos s/n, 09001 Burgos, Spain.  3. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá , 28871 Alcalá de Henares, Madrid, Spain.

Abstract

1,3-Dien-5-ynes have been extensively used as starting materials for the synthesis of a wide number of different carbo- and heterocycles. The aim of this review is to give an overview of their utility in organic synthesis, highlighting the variety of compounds that can be directly accessed from single reactions over these systems. Thus, cycloaromatization processes are initially commented, followed by reactions directed toward the syntheses of five-membered rings, other carbocycles and, finally, heterocycles. The diverse methodologies that have been developed for the synthesis of each of these types of compounds from 1,3-dien-5-ynes are presented, emphasizing the influence of the reaction conditions and the use of additional reagents in the outcome of the transformations.

Publications > Sanjuán et al

Org Lett. 2016 Mar 4;18(5):1072-5. doi: 10.1021/acs.orglett.6b00191.

Formal [4+1] Cycloadditions of β,β-Diaryl-Substituted ortho-(Alkynyl)styrenes through Gold(I)-Catalyzed Cycloisomerization Reactions.

Ana M Sanjuán, Cintia Virumbrales, Patricia García-García, Manuel A Fernández-Rodríguez, Roberto Sanz

Área de Química Orgánica, Departamento de Química, Facultad de Ciencias, Universidad de Burgos , Pza. Misael Bañuelos s/n, 09001-Burgos, Spain.

Abstract

Gold(I)-catalyzed cycloisomerization of β,β-diaryl-o-(alkynyl)styrenes at 80 °C selectively yields dihydroindeno[2,1-a]indenes in a transformation that encompasses a formal [4+1] cycloaddition and takes place through a cascade 5-endo-cyclization-diene activation-iso-Nazarov cyclization. In addition, by performing the reaction at 0 °C, the same substrates exclusively give rise to benzofulvene derivatives, which have also been shown to be intermediates in the formation of the tetracyclics.

Publications > Otero et al

Tetrahedron Lett. 2015; 56(1):195-198. doi: 10.1016/j.tetlet.2014.11.071

Gold-catalyzed synthesis of oxepinones: an experimental mechanistic evidence

Eva M. Otero, Jesús M. Fernández-García, Manuel A. Fernández-Rodríguez, Enrique Aguilar

Palabras clave: Gold catalysis; Oxepinones; Mechanism; π-Acids; Vinylcyclopropenes

Resumen

The isolation of a bicyclic lactone and its room temperature isomerization in CDCl3 to the expected oxepinone allows confirmation of a previously proposed mechanism for the gold-catalyzed synthesis of oxepinones from donor–acceptor alkynylcyclopropanes. However, the unsuccessful conversion of another bicyclic lactone into its corresponding oxepinone points out to a substrate-dependent mechanism.

Publications > Sanjuán et al

Chemistry. 2015 Feb 9;21(7):3042-52. doi: 10.1002/chem.201405789.

Gold(I)-catalyzed cycloisomerizations and alkoxycyclizations of ortho-(alkynyl)styrenes.

Ana M Sanjuán, Muhammad A Rashid, Patricia García-García, Alberto Martínez-Cuezva, Manuel A Fernández-Rodríguez, Félix Rodríguez, Roberto Sanz

Área de Química Orgánica, Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n, 09001 Burgos (Spain) http://www2.ubu.es/ginves/cien_biotec/sintorg/uk/index.htm.

Keywords: asymmetric catalysis; cyclization; cycloisomerization; gold; indenes

Abstract

Indenes and related polycyclic structures have been efficiently synthesized by gold(I)-catalyzed cycloisomerizations of appropriate ortho-(alkynyl)styrenes. Disubstitution at the terminal position of the olefin was demonstrated to be essential to obtain products originating from a formal 5-endo-dig cyclization. Interestingly, a complete switch in the selectivity of the cyclization of o-(alkynyl)-α-methylstyrenes from 6-endo to 5-endo was observed by adding an alcohol to the reaction media. This allowed the synthesis of interesting indenes bearing an all-carbon quaternary center at C1. Moreover, dihydrobenzo%@5Ba%@5Dfluorenes can be obtained from substrates bearing a secondary alkyl group at the β-position of the styrene moiety by a tandem cycloisomerization/1,2-hydride migration process. In addition, diverse polycyclic compounds were obtained by an intramolecular gold-catalyzed alkoxycyclization of o-(alkynyl)styrenes bearing a nucleophile in their structure. Finally, the use of a chiral gold complex allowed access to elusive chiral 1H-indenes in good enantioselectivities.