Amine Radical Cation Research Articles

The Photocatalyzed Aza-Henry Reaction of N-Aryltetrahydroisoquinolines: Comprehensive Mechanism, H•- versus H+-Abstraction, and Background Reactions

The cross-dehydrogenative coupling (CDC) reaction of N-aryltetrahydroisoquinolines (THIQ) is one of the most exploited photocatalytic transformation and a test reaction for an exceptional variety of catalysts. However, its mechanism remained unclear concerning involved intermediates, reactive pathways of the amine radical cation and the influence of oxygen and the light source. Therefore, nuclear magnetic resonance (NMR), electron spin resonance (ESR) and synthetic methods were combined to provide a comprehensive picture of the reaction mechanism using Ru(bpy)3Cl2 as a photocatalyst under aerobic and anaerobic conditions. The reaction profiles and involved intermediates were monitored and analyzed by NMR spectroscopy. Several intermediates contributing to product formation were identified, the iminium ion, the hydroperoxide and dimer of THIQ, and a new ring opened intermediate, cleaved at the benzylic C-N bond. Mechanistic evidence is given that under anaerobic conditions preferentially the α-amino radical is formed by deprotonation, in contrast to the formation of iminium ions via H(•)-abstraction in the presence of oxygen. Further, the light-induced background reaction in the absence of the catalyst was studied in detail, revealing that the product formation rate is correlated to the intensity and wavelength of the light source and that oxygen is essential for an efficient conversion. The reaction rate and efficiency is comparable to previously reported photocatalytic systems, performed under aerobic conditions in combination with intense blue light sources. Thus, the multitude of reaction parameters investigated reveals the preference for hydrogen atom or proton abstraction in photoreactions and allows to assess the influence of experimental conditions on the mechanistic pathways.

The Prowess of Photogenerated Amine Radical Cations in Cascade Reactions: From Carbocycles to Heterocycles.

Cascade reactions represent a class of ideal organic reactions because they empower efficiency, elegance, and novelty. However, development of cascade reactions remains a daunting task for synthetic chemists. Radicals are known to be well suited for cascade reactions. Compared with widely used carbon-based radicals, nitrogen-based radicals, such as neutral aminyl radicals and protonated aminyl radicals (amine radical cations), are underutilized, although they are behind some notable synthetic methods such as the Hofmann-Löffler-Freytag reaction. The constraint on their usage is generally attributed to the limited number of available stable precursors. Since amine radical cations offer increased reactivity and selectivity in chemical transformations compared with neutral aminyl radicals, their generation is of utmost importance. Recently, a surge of reports has been revealed using visible light photoredox catalysis. It has been demonstrated that amines can act as an electron donor in a reductive quenching cycle while the amine itself is oxidized to the amine radical cation. Although a number of methods exist to generate amine radical cations, the photochemical formation of these species offers many practical advantages. In this Account, we discuss our journey to the development of annulation reactions with various π-bonds and electrophilic addition reactions to alkenes using photogenerated amine radical cations. Various carbocycles and heterocycles are produced by these reactions. In our annulation work, we first show that single electron photooxidation of cyclopropylanilines to the amine radical cations triggers ring opening of the strained carbocycle, producing distonic radical cations. These odd-electron species are shown to react with alkenes and alkynes to yield the corresponding cyclopentanes and cyclopentenes in an overall redox neutral process. Further development of this annulation reaction allows us to achieve the [4 + 2] annulation of cyclobutylanilines with alkynes. In our work on electrophilic addition reactions to alkenes, we reveal that photogenerated amine radical cations are capable of undergoing the electrophilic addition reactions to alkenes to form a variety of indoles and indolines. This chemistry represents a rare oxidative C-N bond-forming reaction using visible light. Conclusions drawn from observational results and proposed mechanisms are outlined in this Account. Additionally, open discussion of our successes and deficiencies in our experiences will give readers helpful insights as to how these species tend to react. The overall utility of photogenerated amine radical cations has yet to reach its full potential. With our current results, we anticipate more new transformations can still be derived from the ring opening processes of cyclopropylanilines and cyclobutylanilines under visible light photocatalysis. Additionally, since utilizing photogenerated amine radical cations in C-N bond-forming reactions has practically been absent in literature, we are confident more new reactions have yet been exploited.

Radical Cation and Neutral Radical of Aza-thia[7]helicene with SOMO-HOMO Energy Level Inversion.

We report a relatively persistent, open-shell aza-thia[7]helicene with cross-conjugated electron-rich π-system. The singly occupied molecular orbital (SOMO) energy levels of both radical cation and neutral radical of the [7]helicene are below the highest occupied molecular orbital (HOMO) energy levels, thereby violating the Aufbau principle. The aza-thia[7]helicene is prepared from β-hexathiophene by a three-step one-pot reaction, in which the pyrrole ring is constructed by two consecutive C–N bond formations. Chemical oxidation converts the helicene to its radical cation, while in the presence of base (Cs2CO3), the oxidation gives neutral aminyl radical, likely via proton dissociation from the aminium radical cation with a low pKa. Reaction of the aza-thia[7]helicene with NaH provides the corresponding anion, which shows characteristic cyclic voltammetry wave at anodic peak potential Epa ≈ +0.2 V. Chemical oxidation of the anion with ferrocenium hexafluorophosphate at room temperature gives persistent ne...

Anodic Oxidation of Nitrotriarylamines and Its Implications for Electrocatalysis

In 1980 Steckhan and Schmidt introduced the use of 4,4’,4”-tribromotriphenylamine (1a) and several more highly halogenated derivatives for the electrocatalytic anodic oxidation of organic substrates,1 and a sizeable number of such transformations have been reported.2 The relatively modest oxidation potential of 1 (+0.78 vs Ag/0.1 M AgNO3 reference) imposes restrictions, however, on the range of substrates that can treated in this manner. For this reason, we synthesized a series of triarylamines bearing several electron-withdrawing groups with the expectation that these would be useful for effecting catalytic oxidation of substrates that high oxidation potentials.3 We had found earlier that such substances can be difficult to oxidize anodically.4We have had some success using these more electronegatively substituted triarylamines.5 However, the situation is not as simple as it may appear. For example, the generalization is often made that mediated oxidation can be effected at potentials up to 500-600 mv positive of the oxidation potential of the substrate, but the latter depends, inter alia, upon the rate of further chemical reaction of the oxidized form of the substrate. Other assumptions are that electronegative substituents increase the oxidative power of the triarylamine catalyst, but not any of its other chemical properties and that the amine cation radical is stable on the time scale of the electrolysis. As we will report here, we find that both of these assumptions are often unwarranted for triarylamines. We recently carried out a series of controlled potential electrolyses of a 10:1 mole ratio of trans-stilbene and 4,4’,4”-trimethyl-2,2’,2”-trinitrotriphenylamine (1b) in aqueous acetonitrile. Under these conditions it was found that the initially produced dark blue solution of 1b+ (the cation radical of 1b) quickly turns first violet and then red and much unreacted stilbene remains. The color change demonstrated that 1 + is unstable under these conditions. A subsequent electrolysis of 1 in the absence of stilbene, followed by flash chromatography of the electrolysis mixture afforded a red solid whose formula (from exact mass measurement by mass spectrometry) is C21H16N4O8. We assign structure 2 (a substituted N-phenylphenoxazine) to this substance because a reasonable mechanistic path to it can be written involving three consecutive ECE processes involving nucleophilic attack by water upon 1 +to introduce the oxygen atoms onto the rings.One might conclude from this that the presence of three highly withdrawing nitro groups in 1 + is responsible for its instability by increasing its electrophilicity and that a less highly nitrated derivative would not take this path. This is not so; more recently, we have found that anodic oxidation of the mononitro triphenylamine 1c in aqueous acetonitrile under the same conditions also affords a red substance to which we again assign a phenoxazine structure. Although 1b and 1c both exhibit reversible cyclic voltammograms, this is misleading. In fact, the cation radicals from both 1b and 1c both undergo rather efficient nucleophilic attack by water in experiments of longer time scale. Phenoxazine formation is apparently efficient from 1c even though its oxidation potential is much lower than that of 1b. Decomposition of triphenylamine cation radicals may be a general pattern; the tribromide 1a has also been observed to decompose during preparative scale electrolysis.6 Finally, we note that instability of cation radicals, with its concomitant undesirable impact on electrosynthetic applications, may prove to be problematical in other organic electrocatalytic systems, particularly when they bear one or more strongly electron-withdrawing groups.

(Invited) Synthesis and Characterization of Photoactive Porphyrin Electropolymers

The design and development of new polymeric functional material for application in organic optoelectronic devices, like polymer solar cells, is one of the most active areas of research, mainly due to the continuous search for low cost renewable energy sources. Flexibility, solution processability, and short energy payback time, are among the very important characteristics of the organic based materials that make possible their application in large area devices. However, despite the facts that high power conversion efficiencies have been attained with bulk heterojunction structures, and that the potentiality of the organic photovoltaic technology is still huge, to date industrial production and large scale commercialization have not been achieved, a major issue being the transfer of the efficiencies obtained on small area cells to large area modules. Thus, the development of new polymeric materials and devices construction methods are still necessary, in order to find procedures that allow the implementation of this relevant technology. One of the principal difficulties that the use of organic polymers in electronics has to face is the film deposition methodology over the conducting or semiconducting contacts. The most common approaches rely on thermal evaporation and solution-processing methods. However, thermal evaporation requires materials with adequate sublimation capability and thermal stability, properties that are difficult to reach in polymers. Also, solution processes, such as dip - or spin - coating methodologies, require polymeric materials with intrinsic high solubility. On the contrary, electropolymerization of suitable photoelectroactive monomers allows the synthesis and formation of polymeric films in one step, with the possibility to get control over pattern and thickness, two very important aspects in the implantation of industrial processes. In the last years we developed porphyrin polymeric materials, produced by electrochemical methods. These materials exhibited photovoltaic and electrochromic properties. The monomers were planned with the aim to achieve their polymerization through dimerization of the electrochemically generated tryphenyl amine and/or carbazole radical cations, giving rise to tetraphenylbenzidine and/or dicarbazole substructures with hole transport capability. These polymers demonstrate their capacity for the generation of photoinduced charge separated states, with light absorption in a broad region of the visible spectrum, and hold the potentiality for their application in the development of optoelectronic devices.

ChemInform Abstract: The Radical Cation Mediated Cleavage of Catharanthine Leading to the Vinblastine Type Alkaloids: Implications for Total Synthesis and Drug Design

AbstractReview: 67 refs.

ChemInform Abstract: Aromatic C—H Bond Functionalization Induced by Electrochemically in situ Generated Tris(p‐bromophenyl)aminium Radical Cation: Cationic Chain Reactions of Electron‐Rich Aromatics with Enamides.

An effective Friedel-Crafts alkylation reaction of electron-rich aromatics with N-vinylamides, induced by electrochemically in situ-generated TBPA radical cation, has been developed; the resulting adducts are produced in good to excellent yields. In the ex-cell type electrolysis, TBPA is transformed to its oxidized form in situ and subsequently employed as an electron transfer reagent to initiate a cationic chain reaction. An easily recoverable and reusable polymeric ionic liquid-carbon black (PIL-CB) composite was also utilized as a supporting electrolyte for the electrochemical generation of TBPA cation radical, without sacrificing efficiency or stability after four electrolyses. Cyclic voltammetry analysis and the results of control experiments demonstrate that the reaction of electron-rich aromatics and N-vinylamides occurs via a cationic chain reaction, which takes place though an oxidative activation of a C-H bond of electron-rich aromatics instead of oxidation of the N-vinylamide as previously assumed.

Aromatic C–H Bond Functionalization Induced by Electrochemically in Situ Generated Tris(p-bromophenyl)aminium Radical Cation: Cationic Chain Reactions of Electron-Rich Aromatics with Enamides

An effective Friedel-Crafts alkylation reaction of electron-rich aromatics with N-vinylamides, induced by electrochemically in situ-generated TBPA radical cation, has been developed; the resulting adducts are produced in good to excellent yields. In the "ex-cell" type electrolysis, TBPA is transformed to its oxidized form in situ and subsequently employed as an electron transfer reagent to initiate a cationic chain reaction. An easily recoverable and reusable polymeric ionic liquid-carbon black (PIL-CB) composite was also utilized as a supporting electrolyte for the electrochemical generation of TBPA cation radical, without sacrificing efficiency or stability after four electrolyses. Cyclic voltammetry analysis and the results of control experiments demonstrate that the reaction of electron-rich aromatics and N-vinylamides occurs via a cationic chain reaction, which takes place though an oxidative activation of a C-H bond of electron-rich aromatics instead of oxidation of the N-vinylamide as previously assumed.

Diastereoselective Oxidative C-N/C-O and C-N/C-N Bond Formation Tandems Initiated by Visible Light: Synthesis of Fused N-Arylindolines.

The synthesis of fused N-arylindolines using visible light photoredox catalysis has been developed. We previously described that photogenerated amine radical cations generate substituted indoles through an intermediate benzylic carbocation. Herein, we expand the application of this chemistry by trapping the benzylic carbocation with tethered heteronucleophiles. The reactivity of the photogenerated benzylic carbocation is explored and applied to a range of substrates with various electronic characters and ring constraints. The method described provides C2 and C3 fused indolines bearing a tetrasubstituted carbon stereocenter with greater than 99:1 diastereoselectivity in moderate to good yields.

Isomerization of Metastable Amine Radical Cations by Dissociation—Recombination

The metastable molecular ions of primary aliphatic amines branched at C2 can isomerize by cleavage-recombination, thereby facilitating fragmentation reactions that require less energy than simple cleavage of the initial molecular ion. This process complements the reactions described by Audier to account for the conspicuous absence of the conventional a-cleavage among the major fragmentation reactions of the metastable molecular ions of primary amines.

Amine Functionalization via Oxidative Photoredox Catalysis: Methodology Development and Complex Molecule Synthesis.

ConspectusWhile the use of visible light to drive chemical reactivity is of high importance to the development of environmentally benign chemical transformations, the concomitant use of a stoichiometric electron donor or acceptor is often required to steer the desired redox behavior of these systems. The low-cost and ubiquity of tertiary amine bases has led to their widespread use as reductive additives in photoredox catalysis. Early use of trialkylamines in this context was focused on their role as reductive excited state quenchers of the photocatalyst, which in turn provides a more highly reducing catalytic intermediate.In this Account, we discuss some of the observations and thought processes that have led from our use of amines as reductive additives to their use as complex substrates and intermediates for natural product synthesis. Early attempts by our group to construct key carbon–carbon bonds via free-radical intermediates led to the observation that some trialkylamines readily behave as efficient hydrogen atom donors under redox-active photochemical conditions. In the wake of in-depth mechanistic studies published in the 1970s, 1980s and 1990s, this understanding has in turn allowed for a systematic approach to the design of a number of photochemical methodologies through rational tuning of the amine component. Minimization of the C–H donicity of the amine additive was found to promote desired C–C bond formation in a number of contexts, and subsequent elucidation of the amine’s redox fate has sparked a reevaluation of the amine’s role from that of reagent to that of substrate.The reactivity of tertiary amines in these photochemical systems is complex, and allows for a number of mechanistic possibilities that are not necessarily mutually exclusive. A variety of combinations of single-electron oxidation, C–H abstraction, deprotonation, and β-scission result in the formation of reactive intermediates such as α-amino radicals and iminium ions. These processes have been explored in depth in the photochemical literature and have resulted in a firm mechanistic grasp of the behavior of amine radical cations in fundamental systems. Harnessing the synthetic potential of these transient species represents an ongoing challenge for the controlled functionalization of amine substrates, because these mechanistic possibilities may result in undesired byproduct formation or substrate decomposition. The presence of tertiary amines in numerous alkaloids, pharmaceuticals, and agrochemicals lends credence to the potential utility of this chemistry in natural product synthesis, and herein we will discuss how these transformations might be controlled for synthetic purposes.

ChemInform Abstract: Catalytic Olefin Hydroamination with Aminium Radical Cations: A Photoredox Method for Direct C—N Bond Formation.

While olefin amination with aminium radical cations is a classical method for C–N bond formation, catalytic variants that utilize simple 2° amine precursors remain largely undeveloped. Herein we report a new visible-light photoredox protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins that proceeds through catalytically generated aminium radical intermediates. Mechanistic studies are consistent with a process involving amine oxidation via electron transfer, turnover-limiting C–N bond formation, and a second electron transfer step to reduce a carbon-centered radical, rendering the overall process redox-neutral. A range of structurally diverse N-aryl heterocycles can be prepared in good to excellent yields under conditions significantly milder than those required by conventional aminium-based protocols.

Combining nanosecond and millisecond time scale techniques: determination of thermodynamic and kinetic data of primary alkyl amine cation radicals.

Primary alkyl amines are one of the most commonly used and effective reagents in CO2 capture. Most of the amines used for CO2 capture are recycled, but a minor portion of the amines are degraded after one electron oxidation process, leading to highly toxic substances. The combination of the complementary information obtained from photoinduced electron transfer (flash photolysis) and heterogeneous electron transfer (electrochemistry) appears to be very attractive to fully characterize the electron transfer reaction mechanism of reactive species in general, as well as for determining important thermodynamic properties, such as standard potentials (E°) or pKa values. It is particularly difficult to determine these crucial data accurately in the cases of alkyl primary amines. Hence, in this manuscript we focus on the establishment of the several alkyl primary amines oxidation mechanism in organic aprotic solvents. In order to achieve this, this work combines information provided by flash photolysis (nanosecond), cyclic voltammetry (millisecond), and digital simulation (nanomile-second). Moreover, the accuracy of the E° values calculated using the nanosecond equilibrium method allows not only revising them, but also estimating new important thermodynamic data concerning the bond dissociation energies (BDEs) of ammonium cations (N(+)-H) and of the amine cation radicals (α-C-H), as well as their corresponding pKa values.

The stability of nitrogen-centered radicals.

Radical stabilization energies (RSEs) for a wide variety of nitrogen-centered radicals and their protonated counterparts have been calculated at G3(MP2)-RAD and G3B3 level. The calculated RSE values can be rationalized through the combined effects of resonance delocalization of the unpaired spin, electron donation through adjacent alkyl groups or lone pairs, and through inductive electron donation/electron withdrawal. The influence of ring strain effects as well as the synergistic combination of individual substituent effects (captodatively stabilized N-radicals) have also been explored. In symmetric N-radicals the substituents may also affect the relative ordering of electronic states. In most cases the π-type radical (unpaired spin distribution perpendicular to the plane of the N-radical) is found to be most stable. Closed shell precursors of biological and pharmaceutical relevance, for which neither experimental nor theoretical results on radical stabilities exist, have been included.

Oligotriarylamines with a pyrene core: a multicenter strategy for enhancing radical cation and dication stability and tuning spin distribution.

Monoamine 1, diamines 2-4, triamine 5, and tetraamine 6 have been synthesized by substituting dianisylamino groups at the 1-, 3-, 6-, and/or 8-positions of pyrene. Diamines 2-4 differ in the positions of the amine substituents. No pyrene-pyrene interactions are evident in the single-crystal packing of 3, 4, and 6. With increasing numbers of amine substituents, the first oxidation potential decreases progressively from the mono- to the tetraamine. These compounds show intense charge-transfer (CT) emission in CH2 Cl2 at around 530 nm with quantum yields of 48-68 %. Upon stepwise oxidation by electrolysis or chemical oxidation, these compounds were transformed into radical cations 1(⋅+) -6(⋅+) and dications 2(2+) -6(2+) , which feature strong visible and near-infrared absorptions. Time-dependent density functional theory studies suggested the presence of localized transitions from the pyrene radical cation and aminium radical cation, intervalence CT, and CT between the pyrene and amine moieties. Spectroscopic studies indicated that these radical cations and dications have good stability. Triamine 5 and tetraamine 6 formed efficient CT complexes with tetracyanoquinodimethane in solution. The results of EPR spectroscopy and density functional theory calculations suggested that the dications 2(2+) -4(2+) have a triplet ground state, whereas 5(2+) and 6(2+) have a singlet ground state. The dication of 1,3-disubstituted diamine 4 exhibits a strong EPR signal.

Ruthenium-bis-terpyridine Complex with Two Redox-Asymmetric Amine Substituents: Potential-Controlled Reversal of the Direction of Charge-Transfer

A ruthenium-bis-terpyridine complex [Ru(NPhtpy)(Ntpy)]2+ (22+) with two redox-asymmetric amine units has been prepared, where NPhtpy is 4′-(di-p-anisylaminophen-4-yl)-2,2′:6′,2″-terpyridine and Ntpy is 4′-(di-p-anisylamino)-2,2′:6′,2″-terpyridine. This complex displays two consecutive redox couples at +0.82 and +1.02 V vs Ag/AgCl, which are assigned to the N•+/0 processes of the amine components of the NPhtpy and Ntpy ligands, respectively. The mono-oxidized complex 23+ obtained by oxidative electrolysis shows the presence of the charge transfer from ruthenium(II) to the oxidized aminium radical cation of the NPhtpy ligand (MNNPhtpyCT) around 1000 nm. In the dioxidized form (24+), the MNNPhtpyCT transition decreased distinctly and an opposite charge transfer from ruthenium(II) to the oxidized aminium radical cation of the Ntpy ligand (MNNtpyCT) appeared at 1380 nm. Complexes [Ru(NPhtpy)(tpy)]2+ (tpy is 2,2′:6′,2″-terpyridine), [Ru(Ntpy)(tpy)]2+, and [Ru(NPhtpy)2]2+ have been prepared and studied for the purpose of comparison. TDDFT calculations show that the involvement of the intraligand charge transfer from both NPhtpy and Ntpy ligands is responsible for the enhancement of the visible absorptions of these complexes with respect to [Ru(tpy)2]2+. DFT and TDDFT calculations have been performed on 23+ and 24+ to provide information on the spin distributions and the nature of the near-infrared absorptions. Complex 23+ shows an isotropic EPR signal at room temperature, consistent with an unpaired electron localized on the nitrogen atom.

Catalytic olefin hydroamination with aminium radical cations: a photoredox method for direct C-N bond formation.

While olefin amination with aminium radical cations is a classical method for C-N bond formation, catalytic variants that utilize simple 2° amine precursors remain largely undeveloped. Herein we report a new visible-light photoredox protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins that proceeds through catalytically generated aminium radical intermediates. Mechanistic studies are consistent with a process involving amine oxidation via electron transfer, turnover-limiting C-N bond formation, and a second electron transfer step to reduce a carbon-centered radical, rendering the overall process redox-neutral. A range of structurally diverse N-aryl heterocycles can be prepared in good to excellent yields under conditions significantly milder than those required by conventional aminium-based protocols.

Amine-derivatized calix[4]arenes for sensitive extraction of cupric ion and formation of amine radical cation

We report herein some calix[4]arene amine (C[4]A) derivatives, which are the copper(II)-induced fluorescence “turn-off” and “naked eye” chemosensors and the agents for the formation of amine radical intermediates. In this way, concurrently, the sensitive extraction of cupric ions and the formation of amine radical cations with calixarenes have been documented for the first time. These data were confirmed by using some experimental studies such as UV–visible, fluorescence, electron spin resonance, and cyclic voltammetric.

Photoinduced color change and photomechanical effect of naphthalene diimides bearing alkylamine moieties in the solid state.

Photoinduced color change of naphthalene diimides (NDIs) bearing alkylamine moieties has been observed in the solid state. The color change is attributed to the generation of a NDI radical-anion species, which may be formed through a photoinduced electron-transfer process from the alkylamine moiety to the NDI. The photosensitivity of NDIs is highly dependent on the structures of the alkylamine moieties. Crystallographic analysis, kinetic analysis, UV/Vis/NIR spectroscopic measurements, and analysis of the photoproduct suggested that a radical anion was formed through an irreversible process initiated by proton abstraction between an amine radical cation and the neutral amine moiety. The radical anions formed stacks including mixed-valence stacks and radical-anion stacks, as shown by the broad absorption bands in near-IR spectra. These photosensitive NDIs also showed crystal bending upon photoirradiation, which may be associated with a change in the intermolecular distance of the NDI stacks by the formation of monomeric radical anions, mixed-valence stacks, and radical-anion stacks.

ChemInform Abstract: The Chemistry of Amine Radical Cations Produced by Visible Light Photoredox Catalysis

Amine radical cations are highly useful reactive intermediates in amine synthesis. They have displayed several modes of reactivity leading to some highly sought-after synthetic intermediates including iminium ions, α-amino radicals, and distonic ions. One appealing method to access amine radical cations is through one-electron oxidation of the corresponding amines under visible light photoredox conditions. This approach and subsequent chemistries are emerging as a powerful tool in amine synthesis. This article reviews synthetic applications of amine radical cations produced by visible light photocatalysis.