Asymmetric Conjugate Addition of Ketones to Maleimides Organocatalyzed by a Chiral Primary Amine-Salicylamide

Enantioenriched substituted succinimides are interesting compounds, and their asymmetric organocatalytic synthesis by the conjugated addition of ketones to maleimides has been scarcely explored. This study shows the enantioselective conjugate addition of ketones to maleimides organocatalyzed by a simple primary amine-salicylamide derived from a chiral trans-cyclohexane-1,2-diamine, which provides the desired succinimides in good to excellent yields (up to 98%) and with moderate to excellent enantioselectivities (up to 99%).This research was funded by the Spanish Ministerio de Economía, Industria y Competitividad grant number PGC2018-096616-B-I00, the Spanish Ministerio de Ciencia, Innovación y Universidades (CTQ201788171-P) and the University of Alicante (VIGROB-173)

Visible light-promoted metal-free aerobic photooxidation of xanthenes, thioxanthenes and dihydroacridines in deep eutectic solvents

Benzylic systems such as 9H-xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines can be easily oxidized to the corresponding xanthones, thioxanthones or acridones, respectively, in deep eutectic solvents by a visible blue light-promoted photooxidation procedure carried out using ambient air as oxidant in the presence of riboflavin tetraacetate as a metal-free photocatalyst. The obtained yields are high or almost quantitative, and the reaction media can be recovered and reused. The environmental friendliness of the protocol is demonstrated based on several green metrics.The authors acknowledge the financial support by the Spanish Ministerio de Ciencia e Innovación (PID2021-127332NB-I00), the Generalitat Valenciana (AICO 2021/013) and the University of Alicante (VIGROB-173 and UAUSTI 2022)

Organocatalytic Enantioselective α-Nitrogenation of α,α-Disubstituted Aldehydes in the Absence of a Solvent

A highly efficient enantioselective α-nitrogenation method of α,α-disubstituted aldehydes with azodicarboxylates promoted by a chiral carbamate-monoprotected cyclohexa-1,2-diamine as organocatalyst has been developed. The process was carried out without any solvent, and the corresponding α,α-disubstituted α-nitrogenated aldehydes were obtained with excellent yields and enantioselectivities up to 99% ee. The sustainability of the procedure was established through the calculation of green metrics, such as EcoScale and E-factor. In addition, theoretical calculations have been used to justify the obtained enantioselectivity sense.This work was funded by the Spanish Ministry of Economy, Industry and Competitiveness (PGC2018-096616-B-I00), the Spanish Ministry of Science and Innovation (PID2019-110008GB-I00), and the University of Alicante (VIGROB-173). We also thank SGIker (UPV/EHU) for providing human and computational resources

Organocatalytic Asymmetric Conjugate Addition of Aldehydes to Maleimides and Nitroalkenes in Deep Eutectic Solvents

A chiral primary amine-salicylamide is used as an organocatalyst for the enantioselective conjugate addition of α,α-disubstituted aldehydes to maleimides and nitroalkenes. The reactions are performed in deep eutectic solvents as reaction media at room temperature, leading to the corresponding adducts with enantioselectivities up to 88% (for maleimides) and 80% (for nitroalkenes). Catalyst and solvent can be recovered and reused.We thank the financial support from the Spanish Ministerio de Economía, Industria y Competitividad (CTQ201788171-P and PGC2018-096616-B-I00) and the University of Alicante (VIGROB-173, UADIF18-20 and UAUSTI18-05)

Enantioselective Michael Addition of Aldehydes to Maleimides Organocatalyzed by a Chiral Primary Amine-Salicylamide

A primary amine-salicylamide derived from chiral trans-cyclohexane-1,2-diamine was used as an organocatalyst for the enantioselective conjugate addition of aldehydes, mainly α,α-disubstituted to N-substituted maleimides. The reaction was performed in toluene as a solvent at room temperature. The corresponding enantioenriched adducts were obtained with high yields and enantioselectivities up to 94%. Theoretical calculations were used to justify the stereoinduction.We thank the financial support from the Spanish Ministerio de Economía, Industria y Competitividad (CTQ2015-66624-P and CTQ201788171-P) and the University of Alicante (VIGROB-173). A.M. thanks SIGMA Clermont Chemistry Engineering Graduate School for an ERASMUS+ fellowship. We also thank the Basque Government (GIC15/03, IT1033-16) for financial support, and IZO/SGI SGIker of UPV/EHU for human and technical support

Organocatalytic systems in enantioselective conjugate addition reactions and photooxidations under visible light

This doctoral thesis focuses on applying different organocatalysts in several enantioselective reactions and aerobic photooxidations using visible light. Chapter 1 describes using a chiral primary amine-salicylamide derived from (1R,2R)-cyclohexane-1,2-diamine as chiral organocatalyst in the asymmetric conjugate Michael addition of aldehydes and ketones to maleimides, giving the corresponding enantioenriched succinimides. The same organocatalyst is used in the enantioselective Michael addition of aldehydes to nitroalkenes, yielding enantiopure γ-nitroaldehydes. Furthermore, these Michael additions of aldehydes to maleimides and nitroalkenes are carried out employing sustainable and environmentally friendly deep eutectic solvents (DES), being able to reuse the catalytic system for several cycles. Chapter 2 describes using a chiral primary-amine monocarbamate derived from (1R,2R)-cyclohexane-1,2-diamine as chiral organocatalyst in the enantioselective α-amination of aldehydes with azodicarboxylates, obtaining the corresponding α,α-disubstituted aldehydes with the absence of solvent under mild conditions. This simple orgacatalytic system’s applicability is demonstrated by preparing a chiral oxazolidinone precursor of amino acids. The reaction is also successfully scaled-up. In addition, theoretical calculations were performed to demonstrate how the absolute configuration of the final adducts is produced. Chapter 3 shows how riboflavin tetraacetate, a cheap vitamin B2 derivative, is an appropriate metal-free photocatalyst in the aerobic photooxidation of xanthenes, thioxanthenes and dihydroacridines under visible light irradiation.This research work has been possible thanks to funding from the Spanish Ministerio de Economía y Competitividad (PGC2018-096616-B-100, CTQ201788171-P), the Generalitat Valenciana (AICO 2021/013) and the University of Alicante (VIGROB-173). The author wishes to express his gratitude to the Institute of Organic Synthesis for a research contract (I-PI/21-20) and to the University of Alicante-Banco Santander consortium for a grant to spend a three-months research period in the Chemistry Interdisciplinary Project research center (ChIP) of the University of Camerino (Italy) under the supervision of Dr. Matteo Tiecco

Synthesis of Xanthones, Thioxanthones and Acridones by a Metal-Free Photocatalytic Oxidation Using Visible Light and Molecular Oxygen

9H-Xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines can be easily oxidized to the corresponding xanthones, thioxanthones and acridones, respectively, by a simple photo-oxidation procedure carried out using molecular oxygen as oxidant under the irradiation of visible blue light and in the presence of riboflavin tetraacetate as a metal-free photocatalyst. The obtained yields are high or quantitative.This research was funded by the Spanish Ministerio de Economía, Industria y Competitividad (PGC2018‐096616‐B‐I00 and CTQ201788171‐P) and the University of Alicante (VIGROB‐173)

Visible Light-Induced Aerobic Oxidative Dehydrogenation of C–N/C–O to C=N/C=O Bonds Using Metal-Free Photocatalysts: Recent Developments

Performing synthetic transformation using visible light as energy source, in the presence of a photocatalyst as a promoter, is currently of high interest, and oxidation reactions carried out under these conditions using oxygen as the final oxidant are particularly convenient from an environmental point of view. This review summarizes the recent developments achieved in the oxidative dehydrogenation of C–N and C–O bonds, leading to C=N and C=O bonds, respectively, using air or pure oxygen as oxidant and metal-free homogeneous or recyclable heterogeneous photocatalysts under visible light irradiation

Visible Light-Induced Aerobic Oxidative Dehydrogenation of C–N/C–O to C=N/C=O Bonds Using Metal-Free Photocatalysts: Recent Developments

Performing synthetic transformation using visible light as energy source, in the presence of a photocatalyst as a promoter, is currently of high interest, and oxidation reactions carried out under these conditions using oxygen as the final oxidant are particularly convenient from an environmental point of view. This review summarizes the recent developments achieved in the oxidative dehydrogenation of C–N and C–O bonds, leading to C=N and C=O bonds, respectively, using air or pure oxygen as oxidant and metal-free homogeneous or recyclable heterogeneous photocatalysts under visible light irradiation.This work was funded by the Spanish Ministry of Economy, Industry and Competitiviness, grant numbers PGC2018-096616-B-I00 and CTQ201788171-P, and the University of Alicante, grant number VIGROB-173