- Exploiting the Reactivity of Fluorinated 2-Arylpyridines in Pd-Catalyzed C-H Bond Arylation for the Preparation of Bright Emitting Iridium(III) Complexes
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Pd-catalyzed C-H bond arylation applied to 2-(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine (1) and 2-(3,5-difluorophenyl)-5-(trifluoromethyl)pyridine (5) allows the access to two families of Ir(III) complexes, charge-neutral and cationic species. The reaction is regioselective since only the C3- or C4-position of the fluorinated phenyl ring of 1 or 5 is readily functionalized - namely the C-H bond flanked by the two fluorine atoms which is the most acidic - which allows the electronic control of the reactive site. A range of electron-withdrawing (CN, CO2Et, C(O)Me) substituents on the aryl group has been incorporated leading to the pro-ligands (1, Ar-2,4-dFppy; 2, Ar = p-C6H4-CN; 3, Ar = p-C6H4-CO2Et; 4, Ar = p-C6H4-C(O)Me; 5, and Ar-3,5-dFppy; 6, Ar = p-C6H4-CO2Et). The unsubstituted complexes F1/G1 and F1/G5 featuring 1 and 5, respectively, as C^N ligands are used as reference complexes. The families of five charge-neutral [Ir(C^N)2(N^O)] complexes (C^N is 2-(5-aryl-(4,6-difluorophenyl)-5-(trifluoromethyl)pyridinato (F2-F4), and 2-(4-aryl-(3,5-difluorophenyl)-5-(trifluoromethyl)pyridinato (F5-F6), N^O = 2-picolinate) and five cationic [Ir(C^N)2(N^N)]PF6 complexes (N^N = dmbpy is 4,4′-dimethyl-2,2′-bipyridine) (G2-G6) were synthesized, and their structural and photophysical properties were studied with comparison to the unsubstituted analogues used as reference complexes. The appended aryl group provides large steric bulk as the biaryl fragment is twisted as shown by the X-ray crystal structures of F2, F5, F6, G3, and G5. These latter complexes display a wide variety of different Ir···Ir intermetallic distances in crystals, from 8.150 ? up to 15.034 ?. Moreover, the impact on the emission energy is negligible, as a result of the breaking of the conjugation between the two aryl groups. Charge-neutral complexes [Ir(C^N)2(N^O)] (N^O = 2-picolinate) show bright luminescence: F2-F4 (λem = 495-499 nm) are blue-green emitters, whereas F5 and F6 (λem = 537, 544 nm), where the fluorine substituents are located at the C3- and C5-positions, emit in the green region of the visible spectrum. In all cases, a unitary photoluminescence quantum yield is found. The improvement of φ might be explained by an increase of the radiative rate constant due to a higher degree of rigidity of these congested molecules, compared to the unsubstituted complex F1. The same trends are observed for the family of complexes G. Complexes G1-G4 exhibit blue photoluminescence, and G5 and G6 lead to a red-shifted emission band, as also found for the related complexes F5 and F6 due to the similar fluorine substitution pattern. Their emission quantum yields are remarkably high for charged complexes in the CH2Cl2 solution. These results showed that Pd-catalyzed C-H bond arylation is a valuable synthetic approach for designing efficient emitters with tunable photophysical properties.
- Boyaala, Rabab,Peng, Marie,Tai, Wun-Shan,Touzani, Rachid,Roisnel, Thierry,Dorcet, Vincent,Chi, Yun,Guerchais, Véronique,Doucet, Henri,Soulé, Jean-Fran?ois
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- A Water-Soluble Iridium Photocatalyst for Chemical Modification of Dehydroalanines in Peptides and Proteins
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Dehydroalanine (Dha) residues are attractive noncanonical amino acids that occur naturally in ribosomally synthesised and post-translationally modified peptides (RiPPs). Dha residues are attractive targets for selective late-stage modification of these complex biomolecules. In this work, we show the selective photocatalytic modification of dehydroalanine residues in the antimicrobial peptide nisin and in the proteins small ubiquitin-like modifier (SUMO) and superfolder green fluorescent protein (sfGFP). For this purpose, a new water-soluble iridium(III) photoredox catalyst was used. The design and synthesis of this new photocatalyst, [Ir(dF(CF3)ppy)2(dNMe3bpy)]Cl3, is presented. In contrast to commonly used iridium photocatalysts, this complex is highly water soluble and allows peptides and proteins to be modified in water and aqueous solvents under physiologically relevant conditions, with short reaction times and with low reagent and catalyst loadings. This work suggests that photoredox catalysis using this newly designed catalyst is a promising strategy to modify dehydroalanine-containing natural products and thus could have great potential for novel bioconjugation strategies.
- van Lier, Roos C. W.,de Bruijn, A. Dowine,Roelfes, Gerard
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supporting information
p. 1430 - 1437
(2020/12/11)
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- Base-Activated Latent Heteroaromatic Sulfinates as Nucleophilic Coupling Partners in Palladium-Catalyzed Cross-Coupling Reactions
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Heteroaromatic sulfinates are effective nucleophilic reagents in Pd0-catalyzed cross-coupling reactions with aryl halides. However, metal sulfinate salts can be challenging to purify, solubilize in reaction media, and are not tolerant to multi-step transformations. Here we introduce base-activated, latent sulfinate reagents: β-nitrile and β-ester sulfones. We show that under the cross-coupling conditions, these species generate the sulfinate salt in situ, which then undergo efficient palladium-catalyzed desulfinative cross-coupling with (hetero)aryl bromides to deliver a broad range of biaryls. These latent sulfinate reagents have proven to be stable through multi-step substrate elaboration, and amenable to scale-up.
- Blakemore, David C.,Cook, Xinlan A. F.,Moses, Ian B.,Pantaine, Lo?c R. E.,Sach, Neal W.,Shavnya, Andre,Willis, Michael C.
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p. 22461 - 22468
(2021/09/09)
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- Twofold Radical-Based Synthesis of N, C-Difunctionalized Bicyclo[1.1.1]pentanes
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Bicyclo[1.1.1]pentylamines (BCPAs) are of growing importance to the pharmaceutical industry as sp3-rich bioisosteres of anilines and N-tert-butyl groups. Here we report a facile synthesis of 1,3-disubstituted BCPAs using a twofold radical functionalization strategy. Sulfonamidyl radicals, generated through fragmentation of α-iodoaziridines, undergo initial addition to [1.1.1]propellane to afford iodo-BCPAs; the newly formed C-I bond in these products is then functionalized via a silyl-mediated Giese reaction. This chemistry also translates smoothly to 1,3-disubstituted iodo-BCPs. A wide variety of radical acceptors and iodo-BCPAs are accommodated, providing straightforward access to an array of valuable aniline-like isosteres.
- Anderson, Edward A.,Mousseau, James. J.,Nugent, Jeremy,Owen, Benjamin,Pickford, Helena D.,Smith, Russell C.
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supporting information
p. 9729 - 9736
(2021/07/19)
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- Stereoselective Preparation of C-Aryl Glycosides via Visible-Light-Induced Nickel-Catalyzed Reductive Cross-Coupling of Glycosyl Chlorides and Aryl Bromides
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A nickel-catalyzed cross-coupling reaction of glycosyl chlorides with aryl bromides has been developed. The reaction proceeds smoothly under visible-light irradiation and features the use of bench-stable glycosyl chlorides, allowing the highly stereoselective synthesis of C-aryl glycosides. (Figure presented.).
- Mou, Ze-Dong,Wang, Jia-Xi,Zhang, Xia,Niu, Dawen
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supporting information
p. 3025 - 3029
(2021/05/27)
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- Dearomative Photocatalytic Construction of Bridged 1,3-Diazepanes
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The construction of diverse sp3-rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic construction of 2,7-diazabicyclo[3.2.1]octanes (bridged 1,3-diazepanes) via a reductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4-substituted quinoline substrates, with subsequent Hantzsch ester-promoted reduction to a dihydropyridine intermediate which undergoes in situ two-electron ring closure to form the bridged diazepane architecture. A wide scope of N-arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all-carbon quaternary centers. Computational and experimental mechanistic studies provided insights into the reaction mechanism and observed regioselectivity/diastereoselectivity.
- Dixon, Darren J.,Duarte, Fernanda,Leitch, Jamie A.,Rogova, Tatiana
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supporting information
p. 4121 - 4130
(2020/02/05)
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- Anti-Markovnikov Hydroamination of Unactivated Alkenes with Primary Alkyl Amines
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We report here a photocatalytic method for the intermolecular anti-Markovnikov hydroamination of unactivated olefins with primary alkyl amines to selectively furnish secondary amine products. These reactions proceed through aminium radical cation (ARC) intermediates and occur at room temperature under visible light irradiation in the presence of an iridium photocatalyst and an aryl thiol hydrogen atom donor. Despite the presence of excess olefin, high selectivities are observed for secondary over tertiary amine products, even though the secondary amines are established substrates for ARC-based olefin amination under similar conditions.
- Miller, David C.,Ganley, Jacob M.,Musacchio, Andrew J.,Sherwood, Trevor C.,Ewing, William R.,Knowles, Robert R.
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supporting information
p. 16590 - 16594
(2019/11/03)
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- Photocatalytic Reductive Formation of α-Tertiary Ethers from Ketals
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A general photocatalytic reductive strategy for the construction of unsymmetrical α-tertiary dialkyl ethers is reported. By merging Lewis acid-mediated ketal activation and visible-light photocatalytic reduction, in situ-generated α-alkoxy radicals were found to engage in addition reactions with a variety of olefinic partners. Good reaction efficiency is demonstrated with a range of ketals of aromatic and aliphatic ketones. Extension to acetal substrates is also described, demonstrating the overall synthetic utility of this methodology for complex ether synthesis.
- Rossolini, Thomas,Ferko, Branislav,Dixon, Darren J.
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supporting information
p. 6668 - 6673
(2019/09/03)
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- Fundamentally Different Distance Dependences of Electron-Transfer Rates for Low and High Driving Forces
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The distance dependences of electron-transfer rates (kET) in three homologous series of donor-bridge-acceptor compounds with reaction free energies (ΔGET0) of ca. -1.2, -1.6, and -2.0 eV for thermal charge recombination after initial photoinduced charge separation were studied by transient absorption spectroscopy. In the series with low driving force, the distance dependence is normal and kET decreases upon donor-acceptor distance (rDA) elongation. In the two series with higher driving forces, kET increases with increasing distance over a certain range. This counterintuitive behavior can be explained by a weakly distance-dependent electronic donor-acceptor coupling (HDA) in combination with an increasing reorganization energy (λ). Our study shows that highly exergonic electron transfers can have distance dependences that differ drastically from those of the more commonly investigated weakly exergonic reactions.
- Neumann, Svenja,Wenger, Oliver S.
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supporting information
p. 855 - 860
(2019/01/11)
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- Chemical modification of dehydrated amino acids in natural antimicrobial peptides by photoredox catalysis
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Dehydroalanine (Dha) and dehydrobutyrine (Dhb) are remarkably versatile non-canonical amino acids often found in antimicrobial peptides. This work presents the selective modification of Dha and Dhb in antimicrobial peptides through photocatalytic activation of organoborates under the influence of visible light. Ir(dF(CF3)ppy)2(dtbbpy)PF6 was used as a photoredox catalyst in aqueous solutions for the modification of thiostrepton and nisin. The mild conditions and high selectivity for the dehydrated residues show that photoredox catalysis is a promising tool for the modification of peptide-derived natural products.
- Bruijn, A. Dowine De,Roelfes, Gerard
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supporting information
p. 11314 - 11318
(2018/10/21)
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- Merging Photoredox and Organometallic Catalysts in a Metal–Organic Framework Significantly Boosts Photocatalytic Activities
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Metal–organic frameworks (MOFs) have been extensively used for single-site catalysis and light harvesting, but their application in multicomponent photocatalysis is unexplored. We report here the successful incorporation of an IrIII photoredox catalyst and a NiII cross-coupling catalyst into a stable Zr12 MOF, Zr12-Ir-Ni, to efficiently catalyze C?S bond formation between various aryl iodides and thiols. The proximity of the IrIII and NiII catalytic components to each other (ca. 0.6 nm) in Zr12-Ir-Ni greatly facilitates electron and thiol radical transfers from Ir to Ni centers to reach a turnover number of 38 500, an order of magnitude higher than that of its homogeneous counterpart. This work highlights the opportunity in merging photoredox and organometallic catalysts in MOFs to effect challenging organic transformations.
- Zhu, Yuan-Yuan,Lan, Guangxu,Fan, Yingjie,Veroneau, Samuel S.,Song, Yang,Micheroni, Daniel,Lin, Wenbin
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supporting information
p. 14090 - 14094
(2018/10/15)
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- Intermolecular Anti-Markovnikov Hydroamination of Unactivated Alkenes with Sulfonamides Enabled by Proton-Coupled Electron Transfer
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Here we report a catalytic method for the intermolecular anti-Markovnikov hydroamination of unactivated alkenes using primary and secondary sulfonamides. These reactions occur at room temperature under visible light irradiation and are jointly catalyzed by an iridium(III) photocatalyst, a dialkyl phosphate base, and a thiol hydrogen atom donor. Reaction outcomes are consistent with the intermediacy of an N-centered sulfonamidyl radical generated via proton-coupled electron transfer activation of the sulfonamide N-H bond. Studies outlining the synthetic scope (>60 examples) and mechanistic features of the reaction are presented.
- Zhu, Qilei,Graff, David E.,Knowles, Robert R.
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supporting information
p. 741 - 747
(2018/01/26)
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- Photocatalytic Three-Component Umpolung Synthesis of 1,3-Diamines
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A visible-light-mediated photocatalytic umpolung synthesis of 1,3-diamines from in situ-generated imines and dehydroalanine derivatives is described. Pivoting on a key nucleophilic addition of photocatalytically generated α-amino radicals to electron-deficient alkenes, this three-component coupling reaction affords 1,3-diamines efficiently and diastereoselectively. The mild protocol tolerates a wide variety of functionalities including heterocycles, pinacol boronates, and aliphatic chains. Application to biologically relevant α-amino-γ-lactam synthesis and extension to 1,3-aminoalcohols is also demonstrated.
- Rossolini, Thomas,Leitch, Jamie A.,Grainger, Rachel,Dixon, Darren J.
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supporting information
p. 6794 - 6798
(2018/10/24)
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- Enantioselective Excited-State Photoreactions Controlled by a Chiral Hydrogen-Bonding Iridium Sensitizer
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Stereochemical control of electronically excited states is a long-standing challenge in photochemical synthesis, and few catalytic systems that produce high enantioselectivities in triplet-state photoreactions are known. We report herein an exceptionally effective chiral photocatalyst that recruits prochiral quinolones using a series of hydrogen-bonding and π-π interactions. The organization of these substrates within the chiral environment of the transition-metal photosensitizer leads to efficient Dexter energy transfer and effective stereoinduction. The relative insensitivity of these organometallic chromophores toward ligand modification enables the optimization of this catalyst structure for high enantiomeric excess at catalyst loadings as much as 100-fold lower than the optimal conditions reported for analogous chiral organic photosensitizers.
- Skubi, Kazimer L.,Kidd, Jesse B.,Jung, Hoimin,Guzei, Ilia A.,Baik, Mu-Hyun,Yoon, Tehshik P.
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supporting information
p. 17186 - 17192
(2017/12/06)
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- Microwave-Assisted Synthesis of Heteroleptic Ir(III)+ Polypyridyl Complexes
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We report a rapid, one-pot, operationally simple, and scalable preparation of valuable cationic heteroleptic iridium(III) polypyridyl photosensitizers. This method takes advantage of two consecutive microwave irradiation steps in the same reactor vial, avoiding the need for additional reaction purifications. A number of known heteroleptic iridium(III) complexes are prepared in up to 96% yield. Notably, this method is demonstrated to provide the synthetically versatile photosensitizer [Ir(ppy)2(dtbbpy)]PF6 in >1 g quantities in less than 5 h of bench time. We envision this method will help accelerate future developments in visible-light-dependent chemistry.
- Monos, Timothy M.,Sun, Alexandra C.,McAtee, Rory C.,Devery, James J.,Stephenson, Corey R. J.
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p. 6988 - 6994
(2016/08/30)
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- Catalytic Carbocation Generation Enabled by the Mesolytic Cleavage of Alkoxyamine Radical Cations
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A new catalytic method is described to access carbocation intermediates via the mesolytic cleavage of alkoxyamine radical cations. In this process, electron transfer between an excited state oxidant and a TEMPO-derived alkoxyamine substrate gives rise to a radical cation with a remarkably weak C?O bond. Spontaneous scission results in the formation of the stable nitroxyl radical TEMPO.as well as a reactive carbocation intermediate that can be intercepted by a wide range of nucleophiles. Notably, this process occurs under neutral conditions and at comparatively mild potentials, enabling catalytic cation generation in the presence of both acid sensitive and easily oxidized nucleophilic partners.
- Zhu, Qilei,Gentry, Emily C.,Knowles, Robert R.
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supporting information
p. 9969 - 9973
(2016/08/16)
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- Facile synthesis and complete characterization of homoleptic and heteroleptic cyclometalated Iridium(III) complexes for photocatalysis
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Herein we describe an improved synthesis for homoleptic iridium(III) 2-phenylpyridine based photocatalysts that allows rapid access to these compounds in good to high yields which have recently become a vital component within the field of catalysis. In addition, we synthesized a number of heteroleptic iridium(III) 2-phenylpyridine photocatalysts and report their photophysical and electrochemical properties. The emission energies span the range of 473-560 nm and reduction potentials from -2.27 V to -1.23 V and oxidation potentials ranging from 1.81 V to 0.69 V. Additionally, we provide the calculated excited state properties and comment on the role of these properties in designing catalytic cycles.
- Singh, Anuradha,Teegardin, Kip,Kelly, Megan,Prasad, Kariate S.,Krishnan, Sadagopan,Weaver, Jimmie D.
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- Single-electron transmetalation: An enabling technology for secondary alkylboron cross-coupling
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Single-electron-mediated alkyl transfer affords a novel mechanism for transmetalation, enabling cross-coupling under mild conditions. Here, general conditions are reported for cross-coupling of secondary alkyltrifluoroborates with an array of aryl bromides mediated by an Ir photoredox catalyst and a Ni cross-coupling catalyst.
- Primer, David N.,Karakaya, Idris,Tellis, John C.,Molander, Gary A.
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supporting information
p. 2195 - 2198
(2015/03/04)
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- Photoredox Cross-Coupling: Ir/Ni Dual Catalysis for the Synthesis of Benzylic Ethers
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Single-electron transmetalation has emerged as an enabling paradigm for the cross-coupling of Csp3 hybridized organotrifluoroborates. Cross-coupling of α-alkoxymethyltrifluoroborates with aryl and heteroaryl bromides has been demonstrated by employing dual catalysis with a combination of an iridium photoredox catalyst and a Ni cross-coupling catalyst. The resulting method enables the alkoxymethylation of diverse (hetero)arenes under mild, room-temperature conditions. (Chemical Equation Presented).
- Karakaya, Idris,Primer, David N.,Molander, Gary A.
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supporting information
p. 3294 - 3297
(2015/07/15)
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- Cyclometalated iridium(III) complexes as photosensitizers for long-range electron transfer: Occurrence of a coulomb barrier
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Six cyclometalated iridium(III) complexes were investigated to assess their potential as photosensitizers for long-range electron transfer, and two of them were incorporated directly into covalent donor-bridge-acceptor molecules. The influence of ligarid substitutions on the excited-state properties and the photoredox behavior of the iridium complexes was explored by optical absorption, steady-state and time-resolved luminescence spectroscopy, as well as by electrochemical methods. Bimolecular electron transfer between the photoexcited complexes and 10-methylphenothiazine and methylviologen was found to be only weakly dependent on the ligand substitutions. Intramolecular long-range electron transfer from phenothiazine to photoexcited iridium(III) in the dyads is slow due to the occurrence of a Coulomb barrier. Consequently, an electron-transfer photoproduct is only observable in the transient absorption spectrum, of a donorbridge-acceptor molecule with a fluorinated photosensitizer that exhibits a very long excited-state lifetime. A flashquench technique is necessary for detection of an electrontransfer product in the dyad with a non-fluorinated photosensitizer. The occurrence of a Coulomb barrier associated with intramolecular (excited-state) long-range electron transfer in the dyads with cyclometalated iridium(III) photosensitizers represents an important difference to previously investigated similar donor-bridge-acceptor molecules with photosensitizers based on d6 metal diimine complexes.
- Hanss, David,Freys, Jonathan C.,Bernardinelli, Gerald,Wenger, Oliver S.
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experimental part
p. 4850 - 4859
(2010/05/11)
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