Dual Reactivity Research Articles

Copper(II)-Mediated Dual Reactivity of 2-(5-Phenylisoxazol-3-yl)aniline: Directed Amination and Oxidative C(═O)─C Cleavage of Amides Enabling Direct Access to Urea Derivatives.

The dual reactivity of amides fused to 2-(5-phenylisoxazol-3-yl)aniline as a directing group for the formation of urea derivatives via chemospecific cleavage of the C(═O)─C bond and C(sp2)-H amination is reported here. Employing inexpensive copper as the catalyst and O2 in air as the oxidant, this protocol exhibited broad functional group tolerance for both the transformations. Detailed mechanistic studies and DFT calculations were performed to gain insights into a plausible mechanism for the formation of urea derivatives.

Experimental and DFT analysis of the concentration dependency of corrosion inhibition by a pyridine Schiff base for mild steel in HCl solution

In the present article, we studied the corrosion inhibition of the pyridine Schiff base N, N´-bis(4-dimethylaminobenzaldehyde)-2, 6-pyridinediamine (4-DMBPy) during the corrosion of mild steel AISI 1020 in a 0.1 M HCl solution. The electrochemical analysis by potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) revealed that the Schiff base promotes a protective efficiency up to 81 % at 25 ppm, followed by a decrease at higher concentrations.The Schiff base – surface interactions follow a Freundlich isotherm, indicating a physical adsorption mechanism. The theoretical calculus by Fukui function and dual reactivity descriptors confirmed the physical interaction with mild steel and the low reactivity of the adsorbed species that led to corrosion protection affecting the cathodic and anodic reactions. The quantum calculations by density functional theory (DFT) indicated that protective efficiency decreases due to the tendency to interact with each other. These interactions led to the formation of molecular aggregates and a desorption process. Molecular dynamics (MD) simulations exhibited that the 4-DMBPy molecule preferred to arrange parallel to the Fe (110) surface through physical adsorption. The results were complemented by the scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, and atomic force microscopy (AFM) analyses to reveal the further information about the corrosion process and the effect of the 4-DMBPy Schiff base as a corrosion inhibitor.

The Association of Chronic Pulmonary Aspergillosis and Chronic Pulmonary Histoplasmosis with MDR-TB Patients in Indonesia.

In Indonesia, 2.4% of all new tuberculosis patients had multi-drug resistant disease (MDR-TB); an estimated 24,000 incidences. Historical case series of MDR-TB described a high frequency of cavitation and poor prognosis. The diagnosis of chronic pulmonary aspergillosis (CPA) relies on raised levels of Aspergillus IgG antibodies, and detectable Histoplasma IgG antibodies are suspicious for chronic pulmonary histoplasmosis (CPH). We investigated whether MDR-TB patients might have concurrent CPH or CPA. This was a cross-sectional study with 50 MDR-TB patients. ELISA was used to detect Histoplasma IgG antibodies and lateral flow assay was used to detect Aspergillus IgG/IgM antibodies. Several other possible disease determinants were assessed by multivariate analysis. Of the 50 MDR-TB patients, 14 (28%) and 16 (32%) had positive Histoplasma or Aspergillus serology; six patients (12%) had dual antibody reactivity. Radiological abnormalities in positive patients included diffuse or local infiltrates, nodules, consolidation, and apical cavities, consistent with CPH and CPA. Patients with detectable fungal antibodies tended to have worse disease, and 4 of 26 (15.3%) died in the first 5 months of dual infection (p = 0.11 compared with no deaths in those with only MDR-TB). The criteria for the diagnosis of CPH and CPA were fulfilled in those with moderately and far advanced disease (13 of 14 or 93%) and 12 of 16 (75%), respectively. Damp housing was the only determinant associated with Histoplasma antibodies (PR 2.01; 95%CI 0.56-7.19), while pets were associated with the Aspergillus antibody (PR 18.024; 95%CI 1.594-203.744). CPA or CPH are probably frequent in MDR-TB patients in Indonesia and may carry a worse prognosis.

Elucidating the Key Factors in Hydroamination and Defluoroamination Competitions: A DFT Analysis of Reaction between α‐(Trifluoromethyl)styrene and 2‐Pyridones

Abstractβ‐fluorocarbanions have garnered considerable attention for their dual reactivity in nucleophilic processes and β‐fluorine elimination. In this study, a thorough computational analysis was conducted to explore the reactions of α‐(trifluoromethyl)styrenes with 2‐pyridones to delineate the factors determining protonation or defluorination pathways for the in situ generated β‐fluorocarbanions under varied basic conditions. Our findings illuminate the critical role of organobase basicity in steering the direction of the competitive protonation and β‐fluorine elimination reactions. We propose the use of pKaH values of organobases as a quantitative indicator for discerning the predominant reaction pathways. This provides an efficient approach to predict and control the reaction outcome, facilitating the deliberate design of reactions to leverage the unique reactivity of β‐fluorocarbanions in the realm of fluorine chemistry.

Seroprevalence and Risk Factors Associated with Phleboviruses and Crimean-Congo Hemorrhagic Fever Virus among Blood Donors in Central Tunisia.

The aim of this study was to determine the prevalence of six viruses, from two families of the order Bunyavirales, in the general population of central Tunisia. Sera collected from 377 asymptomatic blood donors were serologically assayed for Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus (CCHFV), and four sandfly-borne phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Cyprus virus (SFCV). Of the 377 subjects enrolled in this study, 17.3% were IgG positive for at least one of the viruses tested. The most frequently detected antibodies were against TOSV (13.3%), followed by SFCV (2.9%), RVFV (1.9%), SFSV (1.3%), and SFNV (1.1%). Only one sample was IgG positive for CCHFV. Dual reactivity was observed in nine cases: SFSV + SFCV in three cases (0.8%) and TOSV + SFNV, TOSV + SFCV, and TOSV + RVFV in two cases (0.5%) each. 15.9% of donors were IgG positive against sandfly-borne phleboviruses. Among the 65 donors IgG positive for phleboviruses, 50.8% were from rural areas compared to 12.3% from urban areas (p < 0.001); 92.3% had animals in their living quarters (p = 0.009); and 70.8% lived in the vicinity of stagnant water (p = 0.062). Seroprevalence was significantly higher among donors living with chronic diseases (p = 0.039). Furthermore, the seroprevalence of phleboviruses was higher in Kairouan, the central governorate, than in the two coastal governorates: Monastir and Sousse, with 33.4%, 24.2%, and 14.9%, respectively. The presence of antibodies in the general population needs further investigation to better assess the extent of these viruses. Only TOSV was known to have an extensive circulation in Tunisia and in North Africa. Continued surveillance and interventions are necessary to detect the emergence of all arboviruses and to prevent further transmission.

Light-Induced Living Polymer Networks with Adaptive Functional Properties.

The advent of covalent adaptable networks (CANs) through the incorporation of dynamic covalent bonds has led to unprecedented properties of macromolecular systems, which can be engineered at the molecular level. Among the various types of stimuli that can be used to trigger chemical changes within polymer networks, light stands out for its remote and spatiotemporal control under ambient conditions. However, most examples of photoactive CANs need to be transparent and they exhibit slow response, side reactions, and limited light penetration. In this vein, it is interesting tounderstand how molecular engineering of optically active dynamic linkages that offer fast response to visible light can impart "living" characteristics to CANs, especially in opaque systems. Here, the use of carbazole-based thiuram disulfides (CTDs) that offer dual reactivity as photoactivated reshuffling linkages and iniferters under visible light irradiation is reported. The fast response to visible light activation of the CTDs leads to temporal control of shape manipulation, healing, and chain extension in the polymer networks, despite the lack of optical transparency. This strategy charts a promising avenue for manipulating multifunctional photoactivated CANs in a controlled manner.

Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-β-lactams, biological evaluations, magic chloro effect and molecular docking studies

A convenient methodology for C-4 indole-β-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-β-lactams assigned with respect to C3-H and C4-H. The synthesized novel β-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term “magic chloro effect”. Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.

Effects of additional ring-fusion site on dual reactivity based dynamic covalent chemistry

Tautomers are widespread in organic chemistry, and their unique reactivity allows diverse transformations. In this work, the incorporation of nearby amide ring-fusion site offered a versatile platform for controlling dual reactivity based dynamic covalent chemistry (DCC) of aldehyde ring-chain tautomers. A suite of 2-formylbenzosulfonamide derived tautomers were prepared, and the intramolecular ring-chain equilibrium and intermolecular dynamic covalent reactions along the underlying mechanistic foundation were investigated. By regulating the substituent electronic effect and solvent effect, ring-chain tautomerization equilibrium was readily regulated in solution. The adjacent amide NH participates in intramolecular hydrogen bonding, as revealed by crystal analysis. Furthermore, the addition of acid and the change of solvent allowed turning on/off the intramolecular cyclization from the amide group to create fused ring scaffolds. Finally, the reversible covalent reactions with amine nucleophile reagents maintained the intermolecular reactivity successfully. The molecular and pathway diversity reported herein sets the scene for future design and applications.

Seropositivity and Trends of Transfusion Section Transmitted Infections among Blood Donors: Five Years Cross-sectional Study on 20,392 Blood Donors in a Tertiary Care Hospital of Ahmedabad, Gujarat, India

Introduction: Blood transfusion is a lifesaving intervention. However, it can also be a source of Transfusion-transmissible Infections (TTIs), posing a potential threat to the recipient. Testing for TTIs before blood transfusion is crucial for the safety of recipients. However, donations occurring during the window period, the prevalence of asymptomatic carriers, viral strains with high genetic variability, and technical errors are responsible for TTIs and remain one of the greatest obstacles in transfusion medicine to deal with. All blood donors are to be screened against five major infections-Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Syphilis, and Malaria. Aim: To study the seroprevalence and trends of TTI among healthy blood donors at the Blood Centre of Ahmedabad, Gujarat, India. Materials and Methods: A cross-sectional study was carried out by reviewing blood donors’ records over a period of five years from January 1, 2018, to December 31, 2022, at the Blood Centre, Department of Pathology, of Sheth L.G. General Hospital, Maninagar, Ahmedabad, Gujarat, India. The data collected for each seropositive donor included the results of TTI testing, the age group of donors, the type of donation, the frequency of donation, and co-infection. The results were expressed in numbers and percentages. Results: Among a total of 20,392 healthy blood donors during the five-year period, the total number of seropositive cases (n) was 243 (1.19%). TTI seropositive donors in years 2018, 2019, 2020, 2021, and 2022 were 60 (1.29%), 50 (1.16%), 39 (1.22%), 45 (1.14%), and 49 (1.16%), respectively. A maximum of 118 (48.56%) seropositive donors were recorded in age group of 18-29 years. Individual seropositive donors during the fiveyear period for HIV, HBV, HCV, syphilis, and malaria were 19 (0.09%), 155 (0.76%), 28 (0.14%), 41 (0.20%), and 00 (0.00%), respectively. Voluntary Blood Donors (VBD) 10,933 (53.61%) exceeded Replacement Donors (RD) 9,459 (46.39%), and repeat blood donors 14,462 (70.92%) surpassed first-time donors 5,930 (29.08%). The seroprevalence of TTI among replacement, voluntary, first-time, and repeat blood donors was 2.41%, 0.14%, 2.06% and 0.84% respectively. Out of 243 seroreactive donors, two donors (0.82%) showed dual reactivity for TTI during the five-year period. Conclusion: Implementation of strict donor selection criteria, utilisation of sensitive screening modalities, promoting public awareness, and dispelling myths regarding the merits of voluntary blood donation, judicious use of blood products, and mass immunisation for Hepatitis B infection are essential interventions needed to curb TTI to a significant extent.

Organic-inorganic covalent-ionic molecules for elastic ceramic plastic.

Although organic-inorganic hybrid materials have played indispensable roles as mechanical1-4, optical5,6, electronic7,8 and biomedical materials9-11, isolated organic-inorganic hybrid molecules (at present limited to covalent compounds12,13) are seldom used to prepare hybrid materials, owing to the distinct behaviours of organic covalent bonds14 and inorganic ionic bonds15 in molecular construction. Here we integrate typical covalent and ionic bonds within one molecule to create an organic-inorganic hybrid molecule, which can be used for bottom-up syntheses of hybrid materials. A combination of the organic covalent thioctic acid (TA) and the inorganic ionic calcium carbonate oligomer (CCO) through an acid-base reaction provides a TA-CCO hybrid molecule with therepresentative molecular formula TA2Ca(CaCO3)2. Its dual reactivity involving copolymerization of the organic TA segment and inorganic CCO segment generates the respective covalent and ionic networks. The two networks are interconnected through TA-CCO complexes to form a covalent-ionic bicontinuous structure within the resulting hybrid material, poly(TA-CCO), which unifies paradoxical mechanical properties. The reversible binding of Ca2+-CO32- bonds in the ionic network and S-S bonds in the covalent network ensures material reprocessability with plastic-like mouldability while preserving thermal stability. The coexistence of ceramic-like, rubber-like and plastic-like behaviours within poly(TA-CCO) goes beyond current classifications of materials to generate an 'elastic ceramic plastic'. The bottom-up creation of organic-inorganic hybrid molecules provides a feasible pathway for the molecular engineering of hybrid materials, thereby supplementing the classical methodology used for the manufacture of organic-inorganic hybrid materials.

Affinity maturation generates pathogenic antibodies with dual reactivity to DNase1L3 and dsDNA in systemic lupus erythematosus

Anti-dsDNA antibodies are pathogenically heterogeneous, implying distinct origins and antigenic properties. Unexpectedly, during the clinical and molecular characterization of autoantibodies to the endonuclease DNase1L3 in patients with systemic lupus erythematosus (SLE), we identified a subset of neutralizing anti-DNase1L3 antibodies previously catalogued as anti-dsDNA. Based on their variable heavy-chain (VH) gene usage, these antibodies can be divided in two groups. One group is encoded by the inherently autoreactive VH4-34 gene segment, derives from anti-DNase1L3 germline-encoded precursors, and gains cross-reactivity to dsDNA – and some additionally to cardiolipin – following somatic hypermutation. The second group, originally defined as nephritogenic anti-dsDNA antibodies, is encoded by diverse VH gene segments. Although affinity maturation results in dual reactivity to DNase1L3 and dsDNA, their binding efficiencies favor DNase1L3 as the primary antigen. Clinical, transcriptional and monoclonal antibody data support that cross-reactive anti-DNase1L3/dsDNA antibodies are more pathogenic than single reactive anti-dsDNA antibodies. These findings point to DNase1L3 as the primary target of a subset of antibodies classified as anti-dsDNA, shedding light on the origin and pathogenic heterogeneity of antibodies reactive to dsDNA in SLE.

Closed-shell and open-shell dual nature of singlet diradical compounds

Abstract Unlike triplet diradicals, singlet diradicals can vary in diradical character from 0 % to 100 % depending on linker units that allow two formally unpaired electrons to couple covalently. In principle, the electronic structure of singlet diradicals can be described as a quantum superposition of closed-shell and open-shell structures. This means that, depending on the external environment, singlet diradicals can behave as either closed-shell or open-shell species. This paper summarizes our progress in understanding the electronic structure of π-conjugated singlet diradical molecules in terms of closed-shell and open-shell dual nature. We first discuss the coexistence of intra- and intermolecular covalent bonding interactions in the π-dimer of a singlet diradical molecule. The intra- and intermolecular coupling of two formally unpaired electrons are related to closed-shell and open-shell nature of singlet diradical, respectively. Then we demonstrate the coexistence of the covalent bonding interactions in the one-dimensional stack of singlet diradical molecules having different diradical character. The relative strength of the interactions is varied with the magnitude of singlet diradical index y 0. Finally, we show the dual reactivity of a singlet diradical molecule, which undergoes rapid [4 + 2] and [4 + 4] cycloaddition reactions in the dark at room temperature. Closed-shell and open-shell nature endow the singlet diradical molecule with the reaction manner as diene and diradical species, respectively.

NO and Heme Proteins: Cross-Talk between Heme and Cysteine Residues

Heme proteins are a diverse group that includes several unrelated families. Their biological function is mainly associated with the reactivity of the heme group, which-among several other reactions-can bind to and react with nitric oxide (NO) and other nitrogen compounds for their production, scavenging, and transport. The S-nitrosylation of cysteine residues, which also results from the reaction with NO and other nitrogen compounds, is a post-translational modification regulating protein activity, with direct effects on a variety of signaling pathways. Heme proteins are unique in exhibiting this dual reactivity toward NO, with reported examples of cross-reactivity between the heme and cysteine residues within the same protein. In this work, we review the literature on this interplay, with particular emphasis on heme proteins in which heme-dependent nitrosylation has been reported and those for which both heme nitrosylation and S-nitrosylation have been associated with biological functions.

Light Alters the NH3 vs N2H4 Product Profile in Iron‐catalyzed Nitrogen Reduction via Dual Reactivity from an Iron Hydrazido (Fe=NNH2) Intermediate

AbstractWhereas synthetically catalyzed nitrogen reduction (N2R) to produce ammonia is widely studied, catalysis to instead produce hydrazine (N2H4) has received less attention despite its considerable mechanistic interest. Herein, we disclose that irradiation of a tris(phosphine)borane (P3B) Fe catalyst, P3BFe+, significantly alters its product profile to increase N2H4 versus NH3; P3BFe+ is otherwise known to be highly selective for NH3. We posit a key terminal hydrazido intermediate, P3BFe=NNH2, as selectivity‐determining. Whereas its singlet ground state undergoes protonation to liberate NH3, a low‐lying triplet excited state leads to reactivity at Nα and formation of N2H4. Associated electrochemical and spectroscopic studies establish that N2H4 lies along a unique product pathway; NH3 is not produced from N2H4. Our findings are distinct from the canonical mechanism for hydrazine formation, which proceeds via a diazene (HN=NH) intermediate and showcase light as a tool to tailor selectivity.

Light Alters the NH3 vs N2 H4 Product Profile in Iron-catalyzed Nitrogen Reduction via Dual Reactivity from an Iron Hydrazido (Fe=NNH2 ) Intermediate.

Whereas synthetically catalyzed nitrogen reduction (N2 R) to produce ammonia is widely studied, catalysis to instead produce hydrazine (N2 H4 ) has received less attention despite its considerable mechanistic interest. Herein, we disclose that irradiation of a tris(phosphine)borane (P3 B ) Fe catalyst, P3 B Fe+ , significantly alters its product profile to increase N2 H4 versus NH3 ; P3 B Fe+ is otherwise known to be highly selective for NH3 . We posit a key terminal hydrazido intermediate, P3 B Fe=NNH2 , as selectivity-determining. Whereas its singlet ground state undergoes protonation to liberate NH3 , a low-lying triplet excited state leads to reactivity at Nα and formation of N2 H4 . Associated electrochemical and spectroscopic studies establish that N2 H4 lies along a unique product pathway; NH3 is not produced from N2 H4 . Our findings are distinct from the canonical mechanism for hydrazine formation, which proceeds via a diazene (HN=NH) intermediate and showcase light as a tool to tailor selectivity.

Organophosphites: An Addition to the Arsenal of Organocatalysts

AbstractOrganophosphites are nucleophilic in nature and can act as a good leaving group owing to the stability of the phosphite anion. This dual reactivity makes them good candidates for nucleophilic organocatalysis. However, phosphites were introduced only in 2004 as the umpolung catalyst for acylsilane substrates utilizing sequential Brook rearrangements. Very recently, phosphites have been reported to catalyze aza‐rearrangements and radical reactions. In this review, we discuss the reactivity parameters to understand its lack of use, as well as the potential for catalysis.

Ligand and metal-centred reactivity in 2,6-bis(imino)-1,4-dihydropyridinate Zn(II) alkyls: the dual behaviour of an intriguing type of complex.

Dihydropyridines, either free or metal-coordinated, are organic hydride transfer reductants that perform on the same premises as the natural redox cofactor NAD(P)+/NAD(P)H. 1-Bn and 1-Me are alkylzinc complexes containing dihydropyridinate-based pincer ligands that have been synthesized through different routes involving the addition of ZnR2 (R = Bn, Me) to the 2,6-bis(imino)-pyridine and 2,6-bis(imino)-4-Bn-dihydropyridine (iPrBIP and 4-BniPrBIPH2) ligands, respectively. The alkyls complexes 1-R react with fluorinated alcohols RFOH (RF = C6F5 or t-C4F9) yielding isolable fluoroalkoxides 2-F5 and 2-F9, in which the reactive 1,4-dihydropyridinate ligand remains unchanged. The crystal structure of 2-F5 shows the shortest Zn⋯F-C interaction reported so far, involving one of the o-F atoms of the C6F5 group. However, the mechanism of the alcoholysis reactions is not straightforward, as NMR monitoring revealed that acidic RFOH first protonates the dihydropyridine nitrogen, releasing the dihydropyridine base 4-BniPrBIPH2 and a highly reactive Zn(R)(ORF) species that re-captures the dihydropyridine in a subsequent step, eliminating the corresponding alkane (R-H). Depending on the mixing conditions, the pincer dihydropyridinate ligand may undergo aromatization to produce the new Zn(II) dialkoxides 3-F5 and 3-F9 stabilised by a neutral iPrBIP ligand [(4R-iPrBIP)Zn(ORF)2]. These protonation and hydride transfer reactions illustrate the dual reactivity of the pincer 1,4-dihydropyridinate zinc entity.

Computational insights into the dual reactivity of 1,2,3,4-tetrazole: a metalloporphyrin-catalyzed click reaction and denitrogenative annulation

The mechanism and origins of chemoselectivities of Mn- and Fe-porphyrin catalyzed click reactions and denitrogenative annulation between 1,2,3,4-tetrazole and phenylacetylene have been studied by density functional theory (DFT) calculations.

Dual reactivity based dynamic covalent chemistry: mechanisms and applications.

Dynamic covalent chemistry (DCC) focuses on the reversible formation, breakage, and exchange of covalent bonds and assemblies, setting a bridge between irreversible organic synthesis and supramolecular chemistry and finding wide utility. In order to enhance structural and functional diversity and complexity, different types of dynamic covalent reactions (DCRs) are placed in one vessel, encompassing orthogonal DCC without crosstalk and communicating DCC with a shared reactive functional group. As a means of adding tautomers, widespread in chemistry, to interconnected DCRs and combining the features of orthogonal and communicating DCRs, a concept of dual reactivity based DCC and underlying structural and mechanistic insights are summarized. The manipulation of the distinct reactivity of structurally diverse ring-chain tautomers allows selective activation and switching of reaction pathways and corresponding DCRs (C-N, C-O, and C-S) and assemblies. The coupling with photoswitches further enables light-mediated formation and scission of multiple types of reversible covalent bonds. To showcase the capability of dual reactivity based DCC, the versatile applications in dynamic polymers and luminescent materials are presented, paving the way for future functionalization studies.

Strategies toward the Difunctionalizations of Enamide Derivatives for Synthesizing α,β-Substituted Amines.

Enamide and enecarbamate derivatives containing a nucleophilic center at the β-position from their nitrogen atom as well as a latent electrophilic site at their α-position are interesting motifs in organic chemistry. This dual reactivity─analogous that of the enamines─enables difunctionalization and increased structural complexity. Furthermore, an electron-withdrawing group on nitrogen drastically increases their stability. In that respect, enamides and enecarbamates are excellent partners for multicomponent transformations, and our research primarily focuses on these compounds in particular.Difunctionalization generally occurs through the nucleophilic addition of the enecarbamate on an electrophile to form iminium, which can subsequently react with a nucleophilic species. Although potent, such an approach is highly challenging due to the low stability of the intermediate iminium, leading to undesired hydrolysis or oligomerization. Epimerization, competitivity, and compatibility issues between the reaction partners are additional hindrances to developing these methodologies. To overcome these limitations, we described many complementary strategies.To control the enantioselectivity of these transformations, chiral phosphoric acids were found to be particularly well-suited to activate multiple reactants due to the formation of a hydrogen bonds network, allowing for an organized transition state in a chiral pocket. Interestingly, when deprotonated as phosphates, they can also play the role of ligands for Lewis acidic metals.To avoid iminium oligomerization, we successfully used stabilized α-arylated enamides. However, this approach was restricted to a simple nucleophilic addition at the β-position. To achieve the difunctionalizations of α-unsubstituted derivatives, we explored reversibly linked nucleophile and electrophile to address their compatibility problem. Alternatively, we devised a sequential methodology for resolving the stability issue of the N-acyl iminium based on its intermediate trapping using a temporary nucleophile (alcohol or thiol). Interestingly, the trapping agent could further be displaced by the desired final α-substituent under Lewis acidic or photocatalytic activation. This led us to design new chiral and bifunctional phosphoric acid catalysts bearing chromophores to merge asymmetric organocatalysis and photochemistry.These photocatalysis studies incited us to focus on radical processes to manage original functionalizations that would not be feasible otherwise. β-Alkylation and β-trifluoromethylation of enecarbamates via visible-light-promoted atom transfer radical additions were successfully performed. As β-allylations remained unattainable with the precedent methods, we eventually turned our attention to cerium(IV)-mediated oxidative single electron transfers. It allowed for singly occupied molecular orbital activation of these substrates to elicit their umpolung reactivity.Thus, the functionalization of enecarbamate derivatives appears as a valid synthetic strategy for obtaining important building blocks for agrochemical, pharmaceutical, and cosmetic industries, including diamines, haloamines, aminotryptamines, and less accessible trifluoromethylated or allylic compounds.