Publications > Humanes et al

Org Lett. 2024, 26, 6568. PubMed 39069746

Selective Synthesis of Boron-Functionalized Indenes and Benzofulvenes by BCl(3)-Promoted Cyclizations of ortho-Alkynylstyrenes.

Marcos Humanes¹, Ester Sans-Panadés¹, Cintia Virumbrales², Ana Milián¹, Roberto Sanz², Patricia García-García¹, Manuel A Fernández-Rodríguez¹

1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá (IRYCIS), 28805 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.

Abstract

A selective, metal-free synthesis of boron-functionalized indenes and benzofulvenes via BCl(3)-mediated cyclization of o-alkynylstyrenes is described. The method allows precise control over product formation by adjusting reaction conditions. These borylated products were utilized in diverse C-B bond derivatizations and in the total synthesis of Sulindac, a nonsteroidal anti-inflammatory drug, demonstrating the versatility and practicality of the developed methodology for synthetic applications.

Publications > Tostado et al

Org Lett. 2024 Apr 26;26(16):3343-3348. doi: 10.1021/acs.orglett.4c00647. Epub 2024 Apr 11. PubMed 38603574

Synthesis of Seven- and Eight-Membered Rings by a Brønsted Acid Catalyzed Cationic Carbocyclization of Biphenyl Embedded Enynes.

Jaime Tostado, Ana Milián, Juan J Vaquero, Manuel A Fernández-Rodríguez

Universidad de Alcalá (IRYCIS). Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Autovía A-II, Km 33.1, 28805-Alcalá de Henares, Madrid, Spain.

Abstract

A Brønsted acid catalyzed cyclization of o-alkenyl-o'-alkynylbiaryls for the synthesis of biologically relevant dibenzo-fused medium-sized rings has been developed. The outcome of the cyclization is determined by the nature of the substituent at the alkyne, with arenes favoring seven-membered rings and alkyl substituents producing eight-membered rings. These reactions proceed via a vinyl cation, which is captured by water and, notably, by C-nucleophiles, such as electron-rich (hetero)arenes.

Publications > Hu et al

Angew Chem Int Ed Engl. 2024, e202319158 PubMed 38506603

Asymmetric, Remote C(sp(3) )-H Arylation via Sulfinyl-Smiles Rearrangement.

Yawen Hu¹, Cédric Hervieu¹, Estíbaliz Merino², Cristina Nevado³

1. Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland.  2. Departamento de Química Orgánica y Química Inorgánica Instituto de Investigación Química "Andrés M. del Río" (IQAR). Facultad de Farmacia, Universidad de Alcalá Alcalá de Henares, 28805, Madrid, Spain.  3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Ctra. de Colmenar Viejo, Km. 9.100, 28034, Madrid, Spain.

Keywords: Asymmetric Remote Arylation; Hydrogen Atom Transfer; Photoredox Catalysis; Sulfinyl-Smiles Rearrangement; α-Arylated Amides

Abstract

An efficient asymmetric remote arylation of C(sp(3) )-H bonds under photoredox conditions is described here. The reaction features the addition radicals to a double bond followed by a site-selective radical translocation (1,n-hydrogen atom transfer) as well as a stereocontrolled aryl migration via sulfinyl-Smiles rearrangement furnishing a wide range of chiral α-arylated amides with up to >99 : 1 er. Mechanistic studies indicate that the sulfinamide group governs the stereochemistry of the product with the aryl migration being the rate determining step preceded by a kinetically favored 1,n-HAT process.

Publications > Mañas and

Org Lett. 2024, 26, 1868 PubMed 38386928

Visible Light-Mediated Heterodifunctionalization of Alkynylazobenzenes for 2H-Indazole Synthesis.

Clara Mañas¹, Estíbaliz Merino²

1. Universidad de Alcalá, Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Andrés del Río (IQAR), Facultad de Farmacia, 28805 Alcalá de Henares, Madrid, Spain.  2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Ctra. de Colmenar Viejo, Km. 9.100, 28034 Madrid, Spain.

Abstract

We disclose the heterodifunctionalization of alkynylazobenzenes promoted exclusively by visible light in the absence of any transition metal and/or photocatalyst. This reaction features excellent regioselectivity on a broad variety of substrates with perfect atom economy. Alcohols, carboxylic acids, thiols, amides, heterocycles, and even water are suitable substrates for the promotion of the oxyamination, sulfenoamination, and diamination reactions. In this manner, biologically active indazole scaffolds can be rapidly assembled from alkyne feedstocks.

Publications > Hervieu et al

Nat Chem. 2024, s41557-023-01414-8. PubMed 38228849

Chiral arylsulfinylamides as reagents for visible light-mediated asymmetric alkene aminoarylations.

Cédric Hervieu¹, Mariia S Kirillova¹, Yawen Hu¹, Sergio Cuesta-Galisteo¹, Estíbaliz Merino^2, a, Cristina Nevado^3, b

1. Department of Chemistry, University of Zurich, Zurich, Switzerland.  2. Universidad de Alcalá, Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Andrés M. del Río (IQAR), Facultad de Farmacia, Madrid, Spain.  3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.

a. estibaliz.merino@uah.es  b. estibaliz.merino@uah.es

Abstract

Two- or one-electron-mediated difunctionalizations of internal alkenes represent straightforward approaches to assemble molecular complexity by the simultaneous formation of two contiguous Csp(3) stereocentres. Although racemic versions have been extensively explored, asymmetric variants, especially those involving open-shell C-centred radical species, are much more limited both in number and scope. Here we describe enantioenriched arylsulfinylamides as all-in-one reagents for the efficient asymmetric, intermolecular aminoarylation of alkenes. Under mild photoredox conditions, nitrogen addition of the arylsulfinylamide onto the double bond, followed by 1,4-translocation of the aromatic ring, produce, in a single operation, the corresponding aminoarylation adducts in enantiomerically enriched form. The sulfinyl group acts here as a traceless chiral auxiliary, as it is eliminated in situ under the mild reaction conditions. Optically pure β,β-diarylethylamines, aryl-α,β-ethylenediamines and α-aryl-β-aminoalcohols, prominent motifs in pharmaceuticals, bioactive natural products and ligands for transition metals, are thereby accessible with excellent levels of regio-, relative and absolute stereocontrol.