Síntese estereoselectiva e asimétrica: conceptos xerais

Titulación: Licenciatura en Química -- Materia: Síntese AsimétricaA Síntese Asimétrica é unha materia optativa incluída no 5º curso da titulación de Licenciatura en Química. A materia está orientada ao alumnado do 5º curso orientados á área de Química Orgánica. Esta unidade didáctica ten o obxectivo de promover o interese do alumno sobre a materia e facilitar a posterior adquisición de coñecementos ó facer fincapé na importancia da síntese asimétrica hoxe en día e facendo un repaso dos conceptos fundamentais acerca do tema adquiridos en cursos anteriores. Os obxectivos da unidade didáctica son: — Comprender a importancia dos contidos da materia de síntese asimétrica no contexto da química orgánica. — Identificar os distintos tipos de isómeros posibles dunha molécula e as consecuencias físico-químicas derivadas. — Utilizar a terminoloxía específica de síntese asimétrica. - Recoñecer os principais métodos de síntese asimétrica (que se desenvolverán nas unidades didácticas posteriores).Universidade de Santiago de Compostela. Servizo de Normalización Lingüístic

Metal-Catalyzed annulations through activation and cleavage of C−H bonds

NOTICE: This is the peer reviewed version of the following article: Moisés Gulías* and José L. Mascareñas* (2016), Metal-Catalyzed Annulations through Activation and Cleavage of C-H Bonds. Angew. Chem. Int. Ed., 55, 11000-11019 [doi:10.1002/anie.201511567 (International Edition), 10.1002/ange.201511567 (German Edition)]. This article may be used for noncommercial purposes in accordance with Wiley Terms and Conditions for self-archivingThe exponential increase in the number of catalytic transformations that involve a metal-promoted activation of hitherto considered inert C−H bonds is promoting a fundamental change in the field of synthetic chemistry. Although most reactions involving C−H activations consist of simple functionalizations or additions, recent years have witnessed an upsurge in related transformations that can be formally considered as cycloaddition processes. These transformations are particularly appealing from a synthetic perspective because they allow the conversion of readily available substrates into highly valuable cyclic products in a rapid and sustainable manner. In many cases, these annulations involve the formation of metallacyclic intermediates that resemble those proposed for standard metal-catalyzed cycloadditions of unsaturated precursorsSpanish MINECO. Grant Number: SAF2013-41943-R. ERDF. European Research Council. Grant Number: 340055. Xunta de Galicia. Grant Numbers: GRC2013-041, 2015-CP082S

Palladium-Catalyzed, Enantioselective Formal Cycloaddition between Benzyltriflamides and Allenes: Straightforward Access to Enantioenriched Isoquinolines

Benzyl and allyltriflamides can engage in Pd-catalyzed oxidative (4+2) annulations with allenes, to produce highly valuable tetrahydroisoquinoline or dihydropyridine skeletons. The reaction is especially efficient when carried out in the presence of designed N-protected amino acids as metal ligands. More importantly, using this type of chiral ligands, it is possible to perform desymmetrizing, annulative C–H activations of prochiral diarylmethylphenyl amides, and thus obtain the corresponding isoquinolines with high enantiomeric ratiosThis work has received financial support from Spanish grants (SAF2016-76689-R, CTQ2016-77047-P and FPU fellowship to X.V.), the Consellería de Cultura, Educación e Ordenación Universitaria (ED431C 2017/19, 2015-CP082 and Centro Singular de Investigación de Galicia accreditation 2016-2019, ED431G/09), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No. 340055)S

Transition-Metal-Catalyzed Annulations Involving the Activation of C(sp3)−H Bonds

The selective functionalization of C(sp3)-H bonds using transitionmetal catalysis is among the more attractive transformations of modern synthetic chemistry. In addition to its inherent atom economy, such reactions open unconventional retrosynthetic pathways that can streamline synthetic processes. However, the activation of intrinsically inert C(sp3)-H bonds, and the selection among very similar C-H bonds, represent highly challenging goals. In recent years there has been notable progress tackling these issues, especially with regard to the development of intermolecular reactions entailing the formation of C-C and C-heteroatom bonds. Conversely, the assembly of cyclic products from simple acyclic precursors using metal-catalyzed C-(sp3)-Hbond activations has been less explored. Only recently has the number of reports on such annulations started to grow. Herein we give an overview of some of the more relevant advances in this exciting topicThis work has received financial support from Spanish grants (PID2019-108624RB-I00, PID2019-110385GB-I00, and Juan de la Cierva-Incorporación fellowship I JCI-2017–31450 to M.F.), the Consellería de Cultura, Educación e Ordenación Universitaria (2021-CP054, ED431C-2021/25 and Centro Singular de Investigación de Galicia accreditation 2019–2022, ED431G2019/03), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No.340055)S

Palladium-Catalyzed Formal (4+2) Cycloaddition between Alkyl Amides and Dienes Initiated by the Activation of C(sp3)−H Bonds

We report a formal (4+2) cycloaddition between alkyl-nosylamides and dienes enabled by a palladium-catalyzed activation of C(sp3)–H bonds beta to the amide group. This atom economical reaction, which proceeds under operationally simple conditions, is compatible with a wide variety of dienes and provides a straightforward method to assemble different types of saturated lactams. The annulation is favored over alternative pathways in part because of the key role of the extra double bond of the diene partner. The use of suitable nitrogen-based additives as palladium ligands, which enable the C(sp3)–H activation without interfering in subsequent steps of the catalytic cycle, is also critical for the success of the reactionThis work has received financial support from Spanish grants (SAF2016-76689-R, CTQ2016-77047-P, and FPI fellowship to B.C. and Juan de la Cierva to M.F.), the Consellerı́a de Cultura, Educación e Ordenación Universitaria (ED431C 2017/19, 2015-CP082 and Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No. 340055). The orfeo-cinqa network CTQ2016-81797-REDC is also kindly acknowledgedS

Rhodium-Catalyzed (5+1) Annulations Between 2-Alkenylphenols and Allenes: A Practical Entry to 2,2-Disubstituted 2H-Chromenes

NOTICE: This is the peer reviewed version of the following article: Casanova, N., Seoane, A., Mascarelas, J. L., Gulías, M. (2015), Rhodium-Catalyzed (5+1) Annulations Between 2-Alkenylphenols and Allenes: A Practical Entry to 2,2-Disubstituted 2H-Chromenes. Angew. Chem. Int. Ed., 54: 2374-2377 [doi: 10.1002/anie.201410350]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archiving.Readily available alkenylphenols react with allenes under rhodium catalysis to provide valuable 2,2-disubstituted 2H-chromenes. The whole process, which involves the cleavage of one C-H bond of the alkenyl moiety and the participation of the allene as a one-carbon cycloaddition partner, can be considered a simple, versatile, and atom-economical (5+1) heteroannulation. The reaction tolerates a broad range of substituents both in the alkenylphenol and in the allene, and most probably proceeds through a mechanism involving a rhodium-catalyzed C-C coupling followed by two sequential pericyclic processes.This work was supported by the Spanish MINECO (grant: SAF2013-41943-R), the ERDF, the European Research Council (Advanced Grant No. 340055), and the Xunta de Galicia (grants: GRC2013-041, EM2013/036 and a Parga Pondal contract to M.G.). We also thank the orfeo-cinqa networkS

Practical, Large-Scale Preparation of Benzoxepines and Coumarins through Rhodium(III)-Catalyzed C–H Activation/Annulation Reactions

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Org. Process Res. Dev., copyright © 2019 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://doi.org/10.1021/acs.oprd.9b00191Herein we disclose the assembly of benzoxepines and coumarins from 2-alkenylphenol precursors using [Cp*RhCl2]2 as the precatalyst and alkynes or carbon monoxide as reacting partners. The preparation of benzoxepines and coumarins can be scaled up to 33 mmol using low catalyst loadingsThis work received financial support from Spanish grants (SAF2016-76689-R, CTQ2016-77047-P, and Juan de la Cierva-Incorporación Fellowship IJCI-2017-31450 to M.F.), the Consellería de Cultura, Educación e Ordenación Universitaria (ED431C 2017/19, 2015-CP082, and Centro Singular de Investigación de Galicia Accreditation 2016–2019, ED431G/09), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant 340055). The orfeo-cinqa network (CTQ2016-81797-REDC) is also kindly acknowledgedS

Rhodium(III)-Catalyzed Intramolecular Annulations of Acrylic and Benzoic Acids to Alkynes

Rh(III) catalysts can promote a formal (4 + 2) intramolecular oxidative annulation between acrylic or benzoic acid derivatives and alkynes. The reaction, which involves a C–H activation process, allows for a rapid assembly of appealing bicyclic pyran-2-ones and tricyclic isocoumarin derivatives in moderate to good yields. The α-pyrone moiety of the products provides for further manipulations to obtain relatively complex cyclic skeletons in a very simple mannerThis work has received financial support from Spanish grants (SAF2016-76689-R, CTQ2016-77047-P, and FPI fellowship to D.F.F.), the Consellería de Cultura, Educación e Ordenación Universitaria (ED431C 2017/19, 2015-CP082, and Centro Singular de Investigación de Galicia acreditación 2016-2019, ED431G/09), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant no. 340055). The orfeo-cinqa network CTQ2016-81797-REDC is also kindly acknowledgedS

Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C–H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines

Enantioenriched, six-membered azacycles are essential structural motifs in many products of pharmaceutical or agrochemical interest. Here we report a simple and practical method for enantioselective assembly of tetrahydropyridines, which is paired to a kinetic resolution of α-branched allyltriflamides. The reaction consists of a formal (4+2) cycloaddition between the allylamine derivatives and allenes and is initiated by a palladium(II)-catalyzed C–H activation process. Both the chiral allylamide precursors and the tetrahydropyridine adducts were successfully obtained in high yields, with excellent enantioselectivity (up to 99% ee) and selectivity values of up to 127This work has received financial support from Spanish grants (SAF2016-76689-R, CTQ2016-77047-P, PID2019-108624RBI00, PID2019-110385GB-I00, and FPI fellowship to B.C.), the Consellería de Cultura, Educación e Ordenación Universitaria (ED431C 2017/19, 2015-CP082 and Centro Singular de Investigación de Galicia accreditation 2019-2022, ED431G 2019/03 and J. M. G fellowship), the European Regional Development Fund (ERDF), and the European Research Council (Advanced Grant No. 340055). The orfeo-cinqa network CTQ2016-81797-REDC is also kindly acknowledgedS

Amide-Directed Formation of Five-Coordinate Osmium Alkylidenes from Alkynes

The amide-directed synthesis of five-coordinate osmium alkylidene derivatives from alkynes is reported. These types of complexes, which have been elusive until now because of the tendency of osmium to give hydride alkylidyne species, are prepared by reaction of the dihydride OsH2Cl2(PiPr3)2 (1) with terminal alkynes containing a distal amide group. Complex 1 reacts with N-phenylhex-5-ynamide and N-phenylhepta-6-ynamide to give OsCl2{═C(CH3)(CH2)nNH(CO)Ph}(PiPr3)2 (n = 3 (2), 4 (3)). The relative position of carbonyl and NH groups in the organic substrates has no influence on the reaction. Thus, treatment of 1 with N-(pent-4-yn-1-yl)benzamide leads to OsCl2{═C(CH3)(CH2)3NHC(O)Ph}(PiPr3)2 (4). The new compounds are intermediate species in the cleavage of the C–C triple bond of the alkynes. Under mild conditions, they undergo the rupture of the Cα–CH3 bond of the alkylidene, which comes from the alkyne triple bond, to afford six-coordinate hydride–alkylidyne derivatives. In dichloromethane, complex 2 gives a 10:7 mixture of OsHCl2{≡C(CH2)3C(O)NHPh}(PiPr3)2 (5) and OsHCl2{≡CCH(CH3)(CH2)2C(O)NHPh}(PiPr3)2 (6). The first complex contains a linear separation between the alkylidyne Cα atom and the amide group, whereas the spacer is branched in the second complex. In contrast to the case for 2, complex 4 selectively affords OsHCl2{≡C(CH2)3NHC(O)Ph}(PiPr3)2 (7). In spite of their instability, these compounds give the alkylidene–allene metathesis, being a useful entry to five-coordinate vinylidene complexes, including the dicarbon-disubstituted OsCl2(═C═CMe2)(PiPr3)2 (8) and the monosubstituted OsCl2(═C═CHCy)(PiPr3)2 (9)Financial support from the Spanish MINECO (Projects CTQ2014-52799-P, SAF2013-41943-R, and CTQ2014-51912-REDC), the DGA (E35), the ERDF, the European Research Council (Advanced Grant No. 340055) and the European Social Fund (FSE), and the Xunta de Galicia (grants GRC2013-041, EM2013/036, 2015-CP082 and a Parga Pondal contract to M.G.) is acknowledge