Enantioselective organocatalyzed aza-Michael addition reaction of 2-hydroxybenzophenone imines to nitroolefins under batch and flow conditions

Herein, an asymmetric organocatalytic aza-Michael addition reaction of ketimines to nitroolefins is presented. The use of 2-hydroxybenzophenone imine improves the enantioselective addition of N-centered nucleophiles to nitroalkenes by means of intramolecular hydrogen bond formation at the imine moiety. Moreover, the versatility of the process is demonstrated under both batch and flow conditions, showing the synthesis of a large variety of nitroamine derivatives with excellent yields and enantioselectivities. In addition, we applied this methodology to the formal synthesis of VNI, a drug-like scaffold for the treatment of Chagas diseaseWe acknowledge the financial support by the Spanish Govern ment (RTI2018-095038-B-I00) and ERC (ERC-CG, 647550, ERC-PoC, Contract No. 861930

2-Hydroxybenzophenone as a Chemical Auxiliary for the Activation of Ketiminoesters for Highly Enantioselective Addition to Nitroalkenes under Bifunctional Catalysis

An organocatalytic system is presented for the Michael addition of monoactivated glycine ketimine ylides with a bifunctional catalyst. The ketimine bears an ortho hydroxy group, which increases the acidity of the methylene hydrogen atoms and enhances the reactivity, thus allowing the synthesis of a large variety of a,g-diamino acid derivatives with excellent stereoselectivit

Intramolecular hydrogen-bond activation for the addition of nucleophilic imines: 2-hydroxybenzophenone as a chemical auxiliary

The addition of nucleophilic imines, using 2-hydroxybenzophenone as a chemical auxiliary, is presented. An intramolecular six-membered ring via hydrogen bonding that enhances the reactivity and selectivity is the key of this strategy, which is supported by DFT calculations and experimental trialsSpanish Government (CTQ2015-64561-R, CTQ2016-76061-P, and MDM-2014-0377), Prodep (UJAT-PTC-247) and CCC-UAM are acknowledged. A. G. thanks MINECO for a PhD fellowship (FPI) and A. M. S. thanks CAM for a postdoctoral contract (2016-T2/IND-1660

Intramolecular hydrogen bond activation: Thiourea-organocatalyzed enantioselective 1,3-dipolar cycloaddition of salicylaldehyde-derived azomethine ylides with nitroalkenes

An organocatalytic strategy for the synthesis of tetrasubstituted pyrrolidines with monoactivated azomethine ylides in high enantiomeric excess and excellent exo/endo selectivity is presented. The key to success is the intramolecular activation via hydrogen bonding through an o-hydroxy group, which allows the dipolar cycloaddition to take place in the presence of azomethine ylides bearing only one activating group. The intramolecular hydrogen bond in the azomethine ylide and the intermolecular hydrogen bond with the catalyst have been demonstrated by DFT calculations and mechanistic proofs to be crucial for the reaction to proceedThe Spanish Government (CTQ2015-64561-R, CTQ2016- 76061-P) and the European Research Council (ERC-CG, contract number 647550) are acknowledged. We acknowledge the generous allocation of computing time at the CCC (UAM). S.D.-T. gratefully acknowledges the “Ramón y Cajal” program (RYC-2010-07019). Financial support from the Spanish Ministry of Economy and Competitiveness, through the “Maria de Maeztu” Program of Excellence in R&D (MDM- 2014-0377

Novel Strategies for the Activation of Nucleophiles and Electrophiles in Asymmetric Organocatalysis

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de Lectura: 03-12-2021Esta tesis tiene embargado el acceso al texto completo hasta el 03-06-2023La financiación para el desarrollo de este trabajo ha provenido del Consejo Europeo de Investigación (ERC-CG, número de contrato 647550), del Ministerio de Ciencia, Innovación y Universidades (RTI2018-095038-B-I00) y de la Comunidad de Madrid y los Fondos Estructurales y de Inversión Europeos (S2018/NMT-4367

Intramolecular Hydrogen-Bond Activation: Strategies, Benefits, and Influence in Catalysis

The activation of molecules through intramolecular hydrogen-bond formation to promote chemical reactions appears as a suitable strategy in organic synthesis, especially for the preparation of chiral compounds under metal and organocatalytic conditions. The use of this interaction has enabled reactivity enhancement of reagents, as well as stabilization of the chemical species and enantiocontrol of the processesFinancial support was provided by the European Research Council (ERC-CoG, Contract No. 647550, ERC-PoC, Contract No. 861930), the Spanish Government (RTI2018- 095038-B-I00), “Comunidad de Madrid”, and European Structural Funds (S2018/NMT-4367) and proyectos sinérgicos I+D (Y2020/NMT-6469). A.G.-C. acknowledges a predoctoral FPI fellowshi

BODIPY as electron withdrawing group for the activation of double bonds in asymmetric cycloaddition reactions

In this work we have found that a BODIPY can be used as an electron withdrawing group for the activation of double bonds in asymmetric catalysis. The synthesis of cyclohexyl derivatives containing a BODIPY unit can easily be achieved via trienamine catalysis. This allows a new different asymmetric synthesis of BODIPY derivatives and opens the door to future transformation of this useful fluorophore. In addition, the Quantum Chemistry calculations and mechanistic studies provide insights into the role of BODIPY as an EWGSpanish Government (CTQ2015-64561-R, CTQ2016-76061-P), CONACYT (project supported by the Fondo Sectorial de Investigación para la Educación) and PRODEP (Mexico) are acknowledged. We acknowledge allocation of computing time at the CCC-UAM. A. G. C. thanks MINECO (FPI) and T. J. P. CONACYT for PhD fellowships, respectively. A. M. S. thanks CAM for a postdoctoral contract (2016-T2/IND-1660). The authors wish to thank ''Comunidad de Madrid'' for its support to the FotoArt-CM Project (S2018/NMT-4367) through the Program of R&D activities between research groups in Technologies 2013, co-financed by European Structural Fund