| Revision as of 22:53, 1 December 2013 editAMayfield (talk | contribs)156 edits →Photochemistry of Transition-Metal Photocatalysts← Previous edit |
Latest revision as of 22:50, 7 February 2023 edit undoDsuke1998AEOS (talk | contribs)Extended confirmed users37,990 edits This redirect has a relatively long page history, part of which was concurrent with Photoredox catalysis's history. I have therefore used both {{R with history}} and {{R from duplicated article}}, in addition to the standard rcats. |
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'''Photoredox catalysis''' is a branch of ] that harnesses the energy of ] to accelerate a ] via a ].<ref>{{cite journal|last=Tucker|first=Joseph W.|coauthors=Stephenson, Corey R. J.|title=Shining Light on Photoredox Catalysis: Theory and Synthetic Applications|journal=The Journal of Organic Chemistry|date=17 February 2012|volume=77|issue=4|pages=1617–1622|doi=10.1021/jo202538x}}</ref> <ref>{{cite journal|last=Prier|first=Christopher K.|coauthors=Rankic, Danica A.; MacMillan, David W. C.|title=Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis|journal=Chemical Reviews|date=10 July 2013|volume=113|issue=7|pages=5322–5363|doi=10.1021/cr300503r}}</ref> This area is named as a combination of “photo-” referring to light and ], a condensed expression for the chemical processes of ] and ]. In particular, photoredox catalysis employs small quantities of a light-sensitive compound that, when excited by light, can mediate the transfer of ] between chemical compounds that otherwise would not react. Photoredox catalysts are generally drawn from three classes of materials: transition-metal complexes, organic dyes, and semiconductors. While each class of materials has advantages, transition-metal complexes are used most often because, unlike semiconductors, they are homogeneous catalysts and because they tend to have stronger redox capabilities than most organic dyes. |
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Study of this branch of catalysis has led to the development of many new methods to accomplish important, but well known, chemical transformations, and additionally has led to the development of new chemical transformations. Some advantages that photoredox catalysts offer in well-known transformations compared to traditional reagents is that photoredox catalysts are often less toxic than other reagents often used to generate ], such as organotin reagents. Furthermore, while photoredox catalysts are potent redox agents while directly exposed to light, they are also very stable to ambient conditions and do not change oxidation state. This can make transition-metal complex photoredox catalysts much easier to work with than stoichiometric redox agents such as quinones. Finally, the properties of photoredox catalysts can be easily modified by changing the type of metal used in the catalyst or by changing one or more of the ligands bound to the metal center. The somewhat modular nature of the catalyst allows straightforward synthesis of a range of analogs and makes it easy to "tune" the catalysts to the needs of a particular chemical system. |
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== Photochemistry of Transition-Metal Photocatalysts == |
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The activity of a photoredox catalyst can be described in three steps. First, a molecule of the catalyst in its ], where the electrons are distributed among the lowest-energy combination of states, interacts with light and moves into a long-lived ], where the electrons are not distributed among the lowest-energy combination of available states. Second, the photoexcited catalyst interacts by an ] process to “quench” the excited state and to activate one of the other components of the chemical reaction. Finally, a second single electron transfer occurs to return the catalyst to its original oxidation state and electron arrangement. |
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The first step of this process, ], is initiated by absorption of a ], promoting an electron from the highest occupied molecular orbital (HOMO) of the photocatalyst to another spin-allowed state. Thus, since the ground state of the photocatalyst is a singlet state (a state with no total ]), the photon absorption excites the catalyst to another singlet state of higher energy. This excitation is realized as a ], where the electron moves from an orbital centered on the metal (e.g. a d orbital) to an orbital localized on the ligands (e.g. the π* orbital of an aromatic ligand). While absorption of a photon can occur for any energy corresponding to the difference between two singlet states, the excited electronic state quickly relaxes to the lowest energy singlet excited state through ], a process where energy is dissipated as vibrational energy rather than as electromagnetic radiation. This singlet excited state can relax further by two distinct processes: the catalyst may ], radiating a photon and returning to the singlet ground state, or it can move to the lowest energy triplet excited state (a state where two unpaired electrons have the same spin) by a second non-radiative process termed ]. Direct relaxation of the excited triplet to the ground state, termed ], requires both emission of a photon and inversion of the spin of the excited electron. The spin-forbidden nature of this pathway means that it is a slow process and therefore that the triplet excited state has a substantial average lifetime. For the common photocatalyst ] (also known as Ru(bipy)<sub>3</sub><sup>2+</sup>), the lifetime of the triplet excited state has been measured to be approximately 1100 ns. This span of time is long enough that other relaxation pathways, specifically electron-transfer pathways, can occur more rapidly than decay of the catalyst to its ground state. |
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The long-lived triplet excited state accessible by photoexcitation is chemically interesting because it is both a more potent ] and a more potent ] than the ground state of the catalyst molecule. In other words, the catalyst can more readily give up one its electrons or accept an electron from an external source. The catalyst excited state is a stronger reductant because its highest energy electron has been excited to an even higher energy state through the photoexcitation process. Similarly, the excited catalyst is a stronger oxidant because one of the catalyst’s lowest energy orbitals, which is fully occupied in the ground state, is only singly occupied after photoexcitation and is therefore available for an external electron to occupy. Since organometallic photocatalysts consist of a coordinatively saturated metal complex, i.e. a structure that cannot form any additional bonds, electron transfer cannot take place by an ] mechanism through a direct bond of the metal complex to another reagent. Instead, electron transfer must take place via an ] process, where the electron ] between the catalyst and another molecule. |
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The ], developed by ], predicts that such a tunneling process will occur most quickly in systems where not only is the electron transfer thermodynamically favorable (i.e. between strong reductants and oxidants) but also where the electron transfer has a low intrinsic barrier. The intrinsic barrier of electron transfer derives from the ], stating that electron transfer takes place more quickly than the atomic nuclei can rearrange. Therefore, immediately after electron transfer, the nuclear arrangement of the molecule exists in a vibrationally excited state and must relax to its new equilibrium geometry. Rigid systems, whose geometry is not greatly dependent on oxidation state, will therefore experience less vibrational excitation during electron transfer, and will have a lower intrinsic barrier. Photocatalysts such as Ru(bipy)3, are held in a rigid arrangement by flat, bidentate ligands arranged in an octahedral geometry around the metal center. Therefore, the complex will not undergo much reorganization during an electron transfer and the process is therefore likely to be fast. Since electron transfer of these complexes is fast, it is very likely to take place within the duration of the catalyst’s active state, i.e. during the lifetime of the triplet excited state. |
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The final step in the photocatalytic cycle is the regeneration of the photocatalyst in its ground state. At this stage, the catalyst exists as the ground state of either its oxidized or reduced forms, depending on whether it acted received or gave up an electron from its photoexcited state. These oxidation states of the catalyst have a strong driving force to return to their equilibrium oxidation state and will act as a potent single-electron reductant or oxidant in order to satisfy that driving force. In order to regenerate the original ground state, the catalyst must participate in a second outer-sphere electron transfer. In many cases, this electron transfer takes place with a stoichiometric two-electron reductant or oxidant, although in some recent cases this step has also been implemented to activate a second reagent. The case where the excited state catalyst first is reduced a reaction component and then is oxidized to return to its resting state is known as a reductive quenching cycle. Conversely the case where the excited state catalyst first is oxidized and then reduced to return to its resting state is known as an oxidative quenching cycle. These two possible cycles can be distinguished by a ]. Since the electron transfer step of the catalytic cycle takes place from the triplet excited state, it competes with phosphorescence as a relaxation pathway. The Stern-Volner experiment measures the intensity of phosphorescence while varying the concentration of each possible quenching agent. When the concentration of the actual quenching agent is varied, the rate of electron transfer therefore the degree of phosphorescence is affected. |
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== Photophysical Properties of Common Photoredox Catalysts == |
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In the study of photoredox catalysis, it is essential to choose a catalyst for which the reduction and oxidation potentials are matched to the other components of the reaction. While ground state redox potentials are easily measured by cyclic voltammetry or other electrochemical methods, measuring the redox potential of an electronically excited state cannot be accomplished directly by these methods.<ref>{{cite journal|last=Jones|first=Wayne E.|coauthors=Fox, Marye Anne|title=Determination of Excited-State Redox Potentials by Phase-Modulated Voltammetry|journal=The Journal of Physical Chemistry|year=1994|month=May|volume=98|issue=19|pages=5095–5099|doi=10.1021/j100070a025}}</ref> However, two methods exist that allow estimation of the excited-state redox potentials and one method exists for the direct measurement of these potentials. To estimate the excited-state redox potentials, one method is to compare the rates of electron transfer from the excited state to a series of ground-state reactants whose redox potentials are known. A more common method to estimate these potentials is to use an equation developed by Rehm and Weller that describes the excited-state potentials as a correction of the ground-state potentials: |
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E*<sub>1/2</sub><sup>red</sup> = E*<sub>1/2</sub><sup>red</sup> + E<sub>0,0</sub> + w<sub>r</sub> |
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E*<sub>1/2</sub><sup>ox</sup> = E*<sub>1/2</sub><sup>ox</sup> - E<sub>0,0</sub> + w<sub>r</sub> |
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In these formulas, E*<sub>1/2</sub> represents the reduction or oxidation potential of the excited state, E<sub>1/2</sub> represents the reduction or oxidation potential of the ground state, E<sub>0,0</sub> represents the difference in energy between the zeroth vibrational states of the ground and excited states, and w<sub>r</sub> represents the work function, an electrostatic interaction that arises due to the separation of charges that occurs during electron-transfer between two chemical species. The zero-zero excitation energy, E<sub>0,0</sub> is usually approximated by the corresponding transition in the fluorescence spectrum. This method allows calculation of approximate excited-state redox potentials from more easily measured ground-state redox potentials and spectroscopic data. |
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Direct measurement of the excited-state redox potentials is possible by applying a method known as phase-modulated voltammetry. This method works by shining light onto an electrochemical cell in order to generate the desired excited-state species, but to modulate the intensity of the light sinusoidally, so that the concentration of the excited-state species is not constant. In fact, the concentration of excited-state species in the cell should change exactly in phase with the intensity of light incident on the electrochemical cell. If the potential applied to the cell is strong enough for electron transfer to occur, the change in concentration of the redox-competent excited state can be measured as an alternating current (AC). Furthermore, the phase shift of the AC current relative to the intensity of the incident light corresponds to the average lifetime of an excited-state species before it engages in electron transfer. |
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! Photocatalyst !! Structure !! E<sub>1/2</sub>(C<sup>+</sup>/C) (V vs SCE) !! E<sub>1/2</sub>(C/C<sup>-</sup>) (V vs SCE) !! E<sub>1/2</sub>(C<sup>+</sup>/C*) (V vs SCE) !! E<sub>1/2</sub>(C*/C<sup>-</sup>) (V vs SCE) !! Excited-State Lifetime (ns) !! Peak Excitation Wavelength (nm) !! Peak Emission Wavelength (nm) !! Reference |
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| tris-(2,2'-bipyrimidine)ruthenium<sup>2+</sup> (Ru(bpm)<sub>3</sub><sup>2+</sup>) || ] || 1.69 || -0.91 || -0.21 || 0.99 || 131 || 454 || 639 ||<ref>{{cite journal|last=Rillema|first=D. Paul|coauthors=Allen, G.; Meyer, T. J.; Conrad, D.|title=Redox properties of ruthenium(II) tris chelate complexes containing the ligands 2,2'-bipyrazine, 2,2'-bipyridine, and 2,2'-bipyrimidine|journal=Inorganic Chemistry|year=1983|volume=22|issue=11|pages=1617-1622}}</ref> |
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| tris-(2,2'-bipyrazine)ruthenium<sup>2+</sup> (Ru(bpz)<sub>3</sub><sup>2+</sup>) || ] || 1.86 || -0.80 || -0.26 || 1.45 || 740 || 443 || 591 ||<ref>{{cite journal|last=Crutchley|first=R. J.|coauthors=Lever, A. B. P.|title=Ruthenium(II) tris(bipyrazyl) dication - a new photocatalyst|journal=Journal of the American Chemical Society|year=1980|month=September|volume=102|issue=23|pages=7128–7129|doi=10.1021/ja00543a053}}</ref> |
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| tris-(2,2'-bipyridine)ruthenium<sup>2+</sup> (Ru(bipy)<sub>3</sub><sup>2+</sup>) || ] || 1.29 || -1.33 || -0.81 || 0.77 || 1100 || 452 || 615 ||<ref>{{cite journal|last=Juris|first=Alberto|coauthors=Balzani, Vincenzo; Belser, Peter; von Zelewsky, Alex|title=Characterization of the Excited State Properties of Some New Photosensitizers of the Ruthenium (Polypyridine) Family|journal=Helvetica Chimica Acta|date=4 November 1981|volume=64|issue=7|pages=2175–2182|doi=10.1002/hlca.19810640723}}</ref> |
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| tris-(1,10-phenanthroline)ruthenium<sup>2+</sup> (Ru(phen)<sub>3</sub><sup>2+</sup>) || ] || 1.26 || -1.36 || -0.87 || 0.82 || 500 || 422 || 610 ||<ref>{{cite journal|last=Young|first=Roger C.|coauthors=Meyer, Thomas J.; Whitten, David G.|title=Electron transfer quenching of excited states of metal complexes|journal=Journal of the American Chemical Society|year=1976|month=January|volume=98|issue=1|pages=286–287|doi=10.1021/ja00417a073}}</ref> |
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| bis-(2-(2',4'-difluorophenyl)-5-trifluoromethylpyridine)(di-tert-butylbipyridine)iridium<sup>+</sup> (Ir(dF(CF<sub>3</sub>)ppy)<sub>2</sub>(dtbbpy)<sup>+<sup>) || ] || 1.69 || -1.37 || -0.89 || 1.21 || 2300 || 380 || 470 ||<ref>{{cite journal|last=Lowry|first=Michael S.|coauthors=Goldsmith, Jonas I.; Slinker, Jason D.; Rohl, Richard; Pascal, Robert A.; Malliaras, George G.; Bernhard, Stefan|title=Single-Layer Electroluminescent Devices and Photoinduced Hydrogen Production from an Ionic Iridium(III) Complex|journal=Chemistry of Materials|year=2005|month=November|volume=17|issue=23|pages=5712–5719|doi=10.1021/cm051312}}</ref> |
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| bis-(2-phenylpyridine)(di-tert-butylbipyridine)iridium<sup>+</sup> (Ir(ppy)<sub>2</sub>(dtbbpy)<sup>+</sup>) || ] || 1.21 || -1.51 || -0.96 || 0.66 || 557 || || 581 ||<ref>{{cite journal|last=Lowry|first=Michael S.|coauthors=Goldsmith, Jonas I.; Slinker, Jason D.; Rohl, Richard; Pascal, Robert A.; Malliaras, George G.; Bernhard, Stefan|title=Single-Layer Electroluminescent Devices and Photoinduced Hydrogen Production from an Ionic Iridium(III) Complex|journal=Chemistry of Materials|year=2005|month=November|volume=17|issue=23|pages=5712–5719|doi=10.1021/cm051312}}</ref> |
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| fac-(tris-(2,2'-phenylpyridine))iridium (Ir(ppy)<sub>3</sub><sup>+</sup>) || ] || 0.77 || -2.19 || -1.73 || 0.31 || 1900 || 375 || 494 ||<ref>{{cite journal|last=Flamigni|first=Lucia|coauthors=Barbieri, Andrea; Sabatini, Cristiana; Ventura, Barbara; Barigelletti, Francesco|title=Photochemistry and Photophysics of Coordination Compounds: Iridium|journal=Topics in Current Chemistry|year=2007|pages=143-203|doi=10.1007/128_2007_131}}</ref> |
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The relative reducing and oxidizing natures of these photocatalysts can be understood intuitively by considering the electronegativity of the ligands and the metal center of the catalyst complex. More electronegative metals and ligands will tend to stabilize electrons better than their less electronegative counterparts. Therefore, complexes with more electronegative complexes will be more easily reduced (i.e. be more powerfully oxidizing) than more electropositive complexes. For example, the ligands 2,2'-bipyridine and 2,2'-phenylpyridine are isoelectronic structures, containing the same number and arrangement of electrons. However, phenylpyridine replaces one of the nitrogen atoms in bipyridine with a carbon atom. Carbon is less electronegative than nitrogen is, so it holds electrons less tightly than nitrogen. Since the remainder of the ligand molecule is identical, this effect is transferred to the structure as a whole: phenylpyridine holds is electrons less tightly than bipyridine, i.e. it is more strongly electron-donating and less electronegative as a ligand. Complexes with phenylpyridine ligands will therefore be more strongly reducing and less strongly oxidizing than complexes with bipyridine ligands because the phenylpyridine complexes are more electron-rich and hold their electrons with slightly less strength. In the same way, a fluorinated derivative of phenylpyridine will be more electronegative than the corresponding simple phenylpyridine and complexes with fluorine-containing ligands will be more strongly oxidizing and less strongly reducing than the unsubstituted phenylpyridine complex. |
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The electronic influence of the metal center on the complex is somewhat more complex than the effect of the ligands. According to the Pauling scale of electronegativity, both ruthenium and iridium have an electronegativity of 2.2. If this was the sole factor relevant to the redox potentials, then complexes of ruthenium and iridium with the same ligands should be equally powerful photoredox catalysts. However, considering the Rehm-Weller equation, the spectroscopic properties of the metal also play a role in determining the redox character of the excited state.<ref>{{cite journal|last=Tucker|first=Joseph W.|coauthors=Stephenson, Corey R. J.|title=Shining Light on Photoredox Catalysis: Theory and Synthetic Applications|journal=The Journal of Organic Chemistry|year=2012|volume=77|issue=4|pages=1617-1622|doi=10.1021/jo202538x}}</ref> In particular, the parameter E<sub>0,0</sub> is related to the emission wavelength of the complex, and therefore to the size of the Stokes shift - the difference in energy between the maximum absorption and emission of a molecule. Ruthenium complexes typically have large Stokes shifts, and therefore have low energy emission wavelengths and small zero-zero excitation energies, when compared to iridium complexes. In effect, this means that although ground-state ruthenium complexes can be potent reductants, that the excited-state complex will be a much less potent reductant or oxidant than a comparable iridium complex. This makes iridium photocatalysts more favorable for the development of general organic transformations because the stronger redox potentials of the excited catalyst allows the use of weaker stoichiometric reductants and oxidants or the use of less reactive substrates.<ref>{{cite journal|last=Tucker|first=Joseph W.|coauthors=Stephenson, Corey R. J.|title=Shining Light on Photoredox Catalysis: Theory and Synthetic Applications|journal=The Journal of Organic Chemistry|year=2012|volume=77|issue=4|pages=1617-1622|doi=10.1021/jo202538x}}</ref> |
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== Applications of Photoredox Catalysis in Organic Chemistry == |
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=== Reductive Dehalogenation === |
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Reductive dehalogenation is a convenient method for removing ] atoms that are introduced into a molecule by a method such as ]. However, the standard method for removing halogen atoms requires the use of stoichiometric ] reagents, such as ]. While this reaction is very powerful and orthogonal to other functional groups commonly present in organic molecules, organotin reagents are highly toxic and the development of alternative reagents is desirable. The cleavage of activated and reductively labile functional groups including sulfoniums and halogens is the earliest application of photoredox catalysis to organic synthesis, but early attempts were hampered by the need for specific or uncommon substrates or by the preferential formation of dimeric coupling products.<ref>{{cite journal|last=Hedstrand|first=David M.|coauthors=Kruizinga, Wim H.; Kellogg, Richard M.|title=Light induced and dye accelerated reductions of phenacyl onium salts by 1,4-dihydropyridines|journal=Tetrahedron Letters|year=1978|month=January|volume=19|issue=14|pages=1255–1258|doi=10.1016/S0040-4039(01)94515-0}}</ref> <ref>{{cite journal|last=Willner|first=Itamar|coauthors=Tsfania, Tamar; Eichen, Yoav|title=Photocatalyzed and electrocatalyzed reduction of vicinal dibromides and activated ketones using ruthenium(I) tris(bipyridine) as electron-transfer mediator|journal=The Journal of Organic Chemistry|year=1990|month=April|volume=55|issue=9|pages=2656–2662|doi=10.1021/jo00296a023}}</ref> <ref>{{cite journal|last=Hironaka|first=Katsuhiko|coauthors=Fukuzumi, Shunichi; Tanaka, Toshio|title=Tris(bipyridyl)ruthenium(II)-photosensitized reaction of 1-benzyl-1,4-dihydronicotinamide with benzyl bromide|journal=Journal of the Chemical Society, Perkin Transactions 2|year=1984|issue=10|pages=1705|doi=10.1039/P29840001705}}</ref> <ref>{{cite journal|last=Kern|first=Jean-Marc|coauthors=Sauvage, Jean-Pierre|title=Photoassisted C?C coupling via electron transfer to benzylic halides by a bis(di-imine) copper(I) complex|journal=Journal of the Chemical Society, Chemical Communications|year=1987|issue=8|pages=546|doi=10.1039/C39870000546}}</ref> <ref>{{cite journal|last=Fukuzumi|first=Shunichi.|coauthors=Mochizuki, Seiji.; Tanaka, Toshio.|title=Photocatalytic reduction of phenacyl halides by 9,10-dihydro-10-methylacridine: control between the reductive and oxidative quenching pathways of tris(bipyridine)ruthenium complex utilizing an acid catalysis|journal=The Journal of Physical Chemistry|year=1990|month=January|volume=94|issue=2|pages=722–726|doi=10.1021/j100365a039}}</ref> Recently, the Stephenson lab developed a more general method for photoredox-mediated reductive dehalogenation.<ref>{{cite journal|last=Narayanam|first=Jagan M. R.|coauthors=Joseph W. Tucker, and Corey R. J. Stephenson|title=Electron-Transfer Photoredox Catalysis: Development of a Tin-Free Reductive Dehalogenation Procedure|journal=JACS|date=06/05/2009|volume=131|issue=25|pages=8756-8757|doi=10.1021/ja9033582|accessdate=10/28/2013}}</ref> Stevenson's original method employs Ru(bipy)<sub>3</sub><sup>2+</sup> as the photocatalyst and a stoichiometric amine reductant to reduce "activated" carbon-halogen bonds, such as those with an adjacent carbonyl group or arene. These bonds are considered to be activated because the radical they produce upon fragmentation is stabilized by conjugation with the carbonyl group or arene, respectively. The stoichiometric reductant present in this reaction transfers an electron to reduce the excited-state catalyst to the Ru(I) oxidation state. The reduced catalyst can then shuttle the transferred electron to the halogenated substrate, reducing the weak C-X bond and inducing fragmentation. |
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In subsequent work published in 2012, Stephenson accomplished the reduction of unactivated carbon-iodine bonds using the strongly reducing photocatalyst tris-(2,2’-phenylpyridine)iridium (Ir(ppy)<sub>3</sub><sup>2+</sup>).<ref>{{cite journal|last=Nguyen|first=John D.|coauthors=D'Amato, Erica M.; Narayanam, Jagan M. R.; Stephenson, Corey R. J.|title=Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated free radical reactions|journal=Nature Chemistry|year=2012|volume=4|issue=10|pages=854-859|doi=10.1038/nchem.1452|accessdate=10/28/2013}}</ref> This updated reaction is mechanistically distinct from the previous transformation of activated bromides and chlorides. In this version of the reaction, fac-Ir(ppy)<sub>3</sub> is used as a photocatalyst. The increased reduction potential of this catalyst compared to Ru(bipy)<sub>3</sub><sup>2+</sup> allows direct reduction of the carbon-iodine bond without first interacting with a stoichiometric reductant. Thus, the iridium complex transfers an electron to the substrate, causing fragmentation of the substrate and oxidizing the catalyst to the Ir(IV) oxidation state. The oxidized photocatalyst is then easily returned to its original oxidation state through interaction with one of the reaction additives. |
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Just as tin-mediated radical dehalogenation reactions can be used to initiate cascade cyclizations to rapidly generate molecular complexity, Stephenson's tin-free reductive dehalogenation allows access to the same types of complex products.<ref>{{cite journal|last=Tucker|first=Joseph W.|coauthors=Nguyen, John D.; Narayanam, Jagan M. R.; Krabbe, Scott W.; Stephenson, Corey R. J.|title=Tin-free radical cyclization reactions initiated by visible light photoredox catalysis|journal=Chemical Communications|date=28 May 2010|volume=46|issue=27|pages=4985-4987|doi=10.1039/c0cc00981d}}</ref> In this work, Stephenson et al. presented a radical cascade cyclization that closed two five-membered rings and formed two new stereocenters, proceeding in good yield. |
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Furthermore, the Stephenson group has made use of their reductive dehalogenation protocol in a key step of their total synthesis of the natural product (+)-Gliocladin C.<ref>{{cite journal|last=Furst|first=Laura|coauthors=Narayanam, Jagan M. R.; Stephenson, Corey R. J.|title=Total Synthesis of (+)-Gliocladin C Enabled by Visible-Light Photoredox Catalysis|journal=Angewandte Chemie International Edition|date=4 October 2011|volume=50|issue=41|pages=9655–9659|doi=10.1002/anie.201103145}}</ref> |
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=== Oxidative Generation of Iminium Ions === |
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] ions are potent ] useful for generating C-N bonds in complex molecules. However, the condensation of ] with ] compounds to form iminium ions is often an unfavorable process, sometimes requiring harsh dehydration conditions. For this reason, alternative methods for the generation of iminium ions, particularly by oxidation from the corresponding amine, is a valuable synthetic tool. The discovery by the Stephenson lab that amines could act as the stoichiometric reductant in their photoredox reductive dehalogenation suggested that photoredox catalysis would be an effective means of oxidatively generating iminium ions from the corresponding amine. In fact, the Stephenson lab achieved the generation of iminium ions from activated amines by the use of Ir(dtbbpy)(ppy)<sub>2</sub>PF<sub>6</sub> as a photoredox catalyst.<ref>{{cite journal|last=Condie|first=Allison G.|coauthors=González-Gómez, José C.; Stephenson, Corey R. J.|title=Visible-Light Photoredox Catalysis: Aza-Henry Reactions via C−H Functionalization|journal=Journal of the American Chemical Society|date=10 February 2010|volume=132|issue=5|pages=1464–1465|doi=10.1021/ja909145y}}</ref> The substrates investigated for this reaction were aryltetrahydroisoquinolines, substrates which would stabilize generation of nitrogen-centered radicals through conjugation with one of the arenes and would promote rapid and regioselective H-atom abstraction to generate the conjugated benzylic imine. Stephenson et al. propose that this transformation occurs by oxidation of the amine to the aminium radical cation by the excited photocatalyst, which is strongly oxidizing due to the electrophilicity of iridium and due to the electron-poor nature of the fluorinated ligands, followed by H-atom transfer to a superstoichimetric oxidant, such as ] (also functioning in the reaction as a nucleophile and as the solvent) or molecular oxygen. Finally, the reactive iminium ion formed by the H-atom transfer is quenched by reaction with any nucleophile present in the reaction. Among the nucleophiles for which photoredox addition to iminium ions has been investigated are nitromethane (aza-]), ] (]), ] (]), allyl silanes (aza-]), and ] (]).<ref>{{cite journal|last=Condie|first=Allison G.|coauthors=González-Gómez, José C.; Stephenson, Corey R. J.|title=Visible-Light Photoredox Catalysis: Aza-Henry Reactions via C−H Functionalization|journal=Journal of the American Chemical Society|date=10 February 2010|volume=132|issue=5|pages=1464–1465|doi=10.1021/ja909145y}}</ref> <ref>{{cite journal|last=Rueping|first=Magnus|coauthors=Zhu, Shaoqun; Koenigs, Rene M.|title=Visible-light photoredox catalyzed oxidative Strecker reaction|journal=Chemical Communications|year=2011|volume=47|pages=12709-12711}}</ref> <ref>{{cite journal|last=Zhao|first=Guolei|coauthors=Yang, Chao; Guo, Lin; Sun, Hongnan; Chen, Chao; Xia, Wujiong|title=Visible light-induced oxidative coupling reaction: easy access to Mannich-type products|journal=Chemical Communications|year=2012|volume=48|pages=2337-2339}}</ref> <ref>{{cite journal|last=Freeman|first=David B.|coauthors=Furst, Laura; Condie, Allison G.; Stephenson, Corey R. J.|title=Functionally Diverse Nucleophilic Trapping of Iminium Intermediates Generated Utilizing Visible Light|journal=Organic Letters|date=6 January 2012|volume=14|issue=1|pages=94–97|doi=10.1021/ol202883v}}</ref> |
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=== Oxidative Generation of Oxocarbenium Ions === |
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The development of orthogonal protecting group chemistry is a crucial problem in organic synthesis because it is the use of these protecting groups that allows each instance of a common functional group, such as the hydroxyl group, to be distinguished during the synthesis of a complex molecule. One very common protecting group for the hydroxyl functional group is the ''para''-methoxy benzyl (PMB) ether. This protecting group is chemically very similar to the less electron-rich benzyl ether. The usual method for selective cleavage of a PMB ether in the presence of a benzyl ether is through the use of strong stoichiometric oxidants such as ] (DDQ) or ] (CAN). PMB ethers are far more susceptible to oxidation than benzyl ethers because they are more electron-rich. Research by Stephenson, et al. has shown that the selective deprotection of PMB ethers can be achieved through the use of bis-(2-(2',4'-difluorophenyl)-5-trifluoromethylpyridine)-(4,4'-ditertbutylbipyridine)iridium(III) hexafluorophosphate (Ir<sub>2</sub>(dtbbpy)PF<sub>6</sub>) and a mild stoichiometric oxidant such as bromotrichloromethane, CBrCl<sub>3</sub>.<ref>{{cite journal|last=Tucker|first=Joseph W.|coauthors=Narayanam, Jagan M. R.; Shah, Pinkey S.; Stephenson, Corey R. J.|title=Oxidative photoredox catalysis: mild and selective deprotection of PMB ethers mediated by visible light|journal=Chemical Communications|year=2011|volume=47|issue=17|pages=5040-5042}}</ref> The photoexcited iridium catalyst is reducing enough to fragment the polyhalomethane compound to form trichloromethyl radical, bromide anion and the Ir(IV) oxidation state of the catalyst. The electron-poor nature of the fluorinated ligands means that this iridium complex can be readily reduced: in particular, by an electron-rich arene such as a para-methoxy benzyl ether. After the arene is oxidized, it will readily participate in H-atom transfer with trichloromethyl radical to form chloroform and an ] ion, which is readily hydrolyzed to reveal the free hydroxide. This reaction was demonstrated to be orthogonal to many common protecting groups, especially with the addition of a base to counteract the buildup of HBr during the reaction. |
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=== Cycloadditions === |
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] and other ] are powerful transforms in organic synthesis because of their potential to rapidly generate complex molecular architectures and particularly because of their capacity to set multiple adjacent ] in a highly controlled manner. However, only certain cycloadditions are allowed under thermal conditions according to the ] of orbital symmetry, or other equivalent models such as ] (FMO) or the Dewar-Zimmermann model. Cycloadditions which are not thermally allowed, such as the cycloaddition, can be enabled by photochemical activation of the reaction. Under uncatalyzed conditions, this activation requires the use of high energy ultraviolet light capable of altering the orbital populations of the reactive compounds. Alternatively, metal catalysts such as cobalt and copper have been reported to catalyze thermally-forbidden cycloadditions via single electron transfer. |
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Recent work by the Yoon lab has demonstrated that the required change in orbital populations can be achieved by electron transfer with a photocatalyst sensitive to lower energy visible light.<ref>{{cite journal|last=Ischay|first=Michael A.|coauthors=Anzovino, Mary E.; Du, Juana; Yoon, Tehshik P.|title=Efficient Visible Light Photocatalysis of Enone Cycloadditions|journal=Journal of the American Chemical Society|year=2008|month=October|volume=130|issue=39|pages=12886–12887|doi=10.1021/ja805387f}}</ref> <ref>{{cite journal|last=Du|first=Juana|coauthors=Yoon, Tehshik P.|title=Crossed Intermolecular Cycloadditions of Acyclic Enones via Visible Light Photocatalysis|journal=Journal of the American Chemical Society|date=21 October 2009|volume=131|issue=41|pages=14604–14605|doi=10.1021/ja903732v}}</ref> <ref>{{cite journal|last=Ischay|first=Michael A.|coauthors=Lu, Zhan; Yoon, Tehshik P.|title= Cycloadditions by Oxidative Visible Light Photocatalysis|journal=Journal of the American Chemical Society|date=30 June 2010|volume=132|issue=25|pages=8572–8574|doi=10.1021/ja103934y}}</ref> <ref>{{cite journal|last=Tyson|first=Elizabeth L.|coauthors=Farney, Elliot P.; Yoon, Tehshik P.|title=Photocatalytic Cycloadditions of Enones with Cleavable Redox Auxiliaries|journal=Organic Letters|date=17 February 2012|volume=14|issue=4|pages=1110–1113|doi=10.1021/ol3000298}}</ref> <ref>{{cite journal|last=Ischay|first=Michael A.|coauthors=Ament, Michael S.; Yoon, Tehshik P.|title=Crossed intermolecular cycloaddition of styrenes by visible light photocatalysis|journal=Chemical Science|year=2012|volume=3|issue=9|pages=2807|doi=10.1039/c2sc20658g}}</ref> Yoon's work has demonstrated the efficient intra- and intermolecular cycloadditions of activated olefins: particularly enones and styrenes. Enones, or electron-poor olefins, were discovered to react via a radical-anion pathway, utilizing diisopropylethylamine as a transient source of electrons. For this electron-transfer, Ru(bipy)<sub>3</sub><sup>2+</sup> was discovered to be an efficient photocatalyst. Interestingly, the anionic nature of the cyclization proved to be crucial: performing the reaction in acid rather than with a lithium counterion favored a non-cycloaddition pathway.<ref>{{cite journal|last=Du|first=Juana|coauthors=Espelt, Laura Ruiz; Guzei, Ilia A.; Yoon, Tehshik P.|title=Photocatalytic reductive cyclizations of enones: Divergent reactivity of photogenerated radical and radical anion intermediates|journal=Chemical Science|year=2011|volume=2|issue=11|pages=2115|doi=10.1039/c1sc00357g}}</ref> Zhao et al. have likewise discovered that a still different cyclization pathway is available to chalcones with a samarium counterion.<ref>{{cite journal|last=Zhao|first=Guolei|coauthors=Yang, Chao; Guo, Lin; Sun, Hongnan; Lin, Run; Xia, Wujiong|title=Reactivity Insight into Reductive Coupling and Aldol Cyclization of Chalcones by Visible Light Photocatalysis|journal=The Journal of Organic Chemistry|date=20 July 2012|volume=77|issue=14|pages=6302–6306|doi=10.1021/jo300796j}}</ref> Conversely, electron-rich styrenes were found to react via a radical-cation mechanism, utilizing methyl viologen or molecular oxygen as a transient electron sink. While Ru(bipy)<sub>3</sub><sup>2+</sup> proved to be a competent catalyst for intramolecular cyclizations using methyl viologen, it could not be used with molecular oxygen as an electron sink or for intermolecular cyclizations. For intermolecular cyclizations, Yoon et al. discovered that the more strongly oxidizing photocatalyst Ru(bpm)<sub>3</sub><sup>2+</sup> and molecular oxygen provided a catalytic system better suited to access the radical cation necessary for the cycloaddition to occur. Ru(bpz)<sub>3</sub><sup>2+</sup>, a still more strongly oxidizing photocatalyst, proved to be problematic because it was not only strong enough to oxidize the reagents and catalyze the desired cycloaddition, but also was strong enough to oxidize the cycloadduct and catalyze the retro- reaction. This comparison of photocatalysts highlights the importance of tuning the redox properties of a photocatalyst to the reaction system as well as demonstrating the value of polypyridyl compounds as ligands due to the ease with which they can be modified to adjust the redox properties of their complexes. |
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Research on photoredox-catalyzed cycloadditions has also been performed by Nicewicz et al. as part of their study of cyclobutane lignans.<ref>{{cite journal|last=Riener|first=Michelle|coauthors=Nicewicz, David A.|title=Synthesis of cyclobutane lignans via an organic single electron oxidant–electron relay system|journal=Chemical Science|year=2013|volume=4|issue=6|pages=2625|doi=10.1039/c3sc50643f}}</ref> |
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In addition to research on the thermally-forbidden cycloaddition, research in the Yoon group has also studied photoredox catalysis of the cyclization, also known as the Diels-Alder reaction. Yoon et al. discovered that bis-enones, similar to the substrates used for the photoredox cyclization, but with a longer linker joining the two enone functional groups, underwent intramolecular radical-anion hetero-Diels-Alder reactions more rapidly than cycloaddition.<ref>{{cite journal|last=Hurtley|first=Anna E.|coauthors=Cismesia, Megan A.; Ischay, Michael A.; Yoon, Tehshik P.|title=Visible light photocatalysis of radical anion hetero-Diels–Alder cycloadditions|journal=Tetrahedron|year=2011|month=June|volume=67|issue=24|pages=4442–4448|doi=10.1016/j.tet.2011.02.066}}</ref> |
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Similarly, Yoon et al. discovered that electron-rich styrenes participated in intra- or intermolecular Diels-Alder cyclizations via a radical cation mechanism.<ref>{{cite journal|last=Lin|first=Shishi|coauthors=Ischay, Michael A.; Fry, Charles G.; Yoon, Tehshik P.|title=Radical Cation Diels–Alder Cycloadditions by Visible Light Photocatalysis|journal=Journal of the American Chemical Society|date=7 December 2011|volume=133|issue=48|pages=19350–19353|doi=10.1021/ja2093579}}</ref> <ref>{{cite journal|last=Lin|first=Shishi|coauthors=Padilla, Christian E.; Ischay, Michael A.; Yoon, Tehshik P.|title=Visible light photocatalysis of intramolecular radical cation Diels–Alder cycloadditions|journal=Tetrahedron Letters|year=2012|month=June|volume=53|issue=24|pages=3073–3076|doi=10.1016/j.tetlet.2012.04.021}}</ref> In contrast to the Yoon's lab discovery that Ru(bipy)<sub>3</sub><sup>2+</sup> was competent for intramolecular, but not intermolecular cyclizations, Yoon et al. discovered that Ru(bipy)<sub>3</sub><sup>2+</sup> was a competent catalyst for intermolecular, but not intramolecular, Diels-Alder cyclizations. One particular advantage of this photoredox-catalyzed Diels-Alder reaction is that it allows cycloaddition between two electronically mismatched substrates. The normal electronic demand for the Diels-Alder reaction calls for an electron-rich diene to react with an electron-poor olefin (or "dienophile"), while the inverse electron-demand Diels-Alder reaction takes place between the opposite case of an electron-poor diene and a very electron-rich dienophile. The photoredox case, since it takes place by a different mechanism than the thermal Diels-Alder reaction, allows cycloaddition between an electron-rich diene and an electron-rich dienophile, allowing access to new classes of Diels-Alder adducts. |
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=== Photoredox Organocatalysis === |
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] is a seperate subfield of catalysis that explores the potential of organic small molecules as catalysts, particularly for the enantioselective creation of chiral molecules. One major strategy in this subfield is the use of chiral secondary amines to activate carbonyl compounds. In this case, condensation of the amine with the carbonyl compound generates a nucleophilic enamine. The chiral amine is designed so that one face of the enamine is sterically shielded and so that only the unshielded face is free to react. Despite the power of this approach to catalyze the enantioselective functionalization of carbonyl compounds, certain valuable transformations, such as the catalytic enantioselective α-alkylation of aldehydes, remained elusive. Recent work by the MacMillan group revealed that the synergistic combination of organocatalysis with photoredox methods provides a simple catalytic solution to this problem.<ref>{{cite journal|last=Nicewicz|first=D. A.|coauthors=MacMillan, D. W. C.|title=Merging Photoredox Catalysis with Organocatalysis: The Direct Asymmetric Alkylation of Aldehydes|journal=Science|date=3 October 2008|volume=322|issue=5898|pages=77–80|doi=10.1126/science.1161976}}</ref> |
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In the MacMillan group's approach for the α-alkylation of aldehydes, Ru(bipy)<sub>3</sub><sup>2+</sup> reductively fragments an activated alkyl halide, such as bromomalonate or phenacyl bromide, which can then add to catalytically-generated enamine in an enantioselective manner. The oxidized photocatalyst then oxidatively quenches the resulting α-amino radical to form an iminium ion, which hydrolyzes to give the functionalized carbonyl compound. This photoredox transformation was shown to be mechanistically distinct from another organocatalytic radical process developed in the MacMillan lab, termed singly-occupied molecular orbital (SOMO) catalysis. The method of SOMO catalysis employs superstoichiometric ceric ammonium nitrate (CAN) to oxidize the catalytically-generated enamine to the corresponding radical cation, which can then add to a suitable coupling partner such as allyl silane. Nicewicz and MacMillan were able to exclude this type of mechanism from the photocatalytic alkylation reaction because whereas enamine radical cation was observed to cyclize onto pendant olefins and open cyclopropane radical clocks in SOMO catalysis, these structures were unreactive in the photoredox reaction. |
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Continued research in the MacMillan has expanded the scope of this transformation to include alkylation with other classes of activated alkyl halides of synthetic interest. In particular, the use of the photocatalyst Ir(dtbbpy)(ppy)<sub>2</sub><sup>+</sup> allowed the direct and enantioselective α-trifluoromethylation of aldehydes while the use of Ir(ppy)<sub>3</sub> allowed the enantioselective coupling of aldehydes with electron-poor benzylic bromides.<ref>{{cite journal|last=Nagib|first=David A.|coauthors=Scott, Mark E.; MacMillan, David W. C.|title=Enantioselective α-Trifluoromethylation of Aldehydes via Photoredox Organocatalysis|journal=Journal of the American Chemical Society|date=12 August 2009|volume=131|issue=31|pages=10875–10877|doi=10.1021/ja9053338}}</ref> <ref>{{cite journal|last=Shih|first=Hui-Wen|coauthors=Vander Wal, Mark N.; Grange, Rebecca L.; MacMillan, David W. C.|title=Enantioselective α-Benzylation of Aldehydes via Photoredox Organocatalysis|journal=Journal of the American Chemical Society|date=6 October 2010|volume=132|issue=39|pages=13600–13603|doi=10.1021/ja106593m}}</ref> |
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MacMillan and coworkers have also developed the first direct β-arylation of saturated aldehydes and ketones through the combination of photoredox and organocatalytic methods.<ref>{{cite journal|last=Pirnot|first=M. T.|coauthors=Rankic, D. A.; Martin, D. B. C.; MacMillan, D. W. C.|title=Photoredox Activation for the Direct -Arylation of Ketones and Aldehydes|journal=Science|date=28 March 2013|volume=339|issue=6127|pages=1593–1596|doi=10.1126/science.1232993}}</ref> The only previous method to accomplish any direct β-functionalization of a saturated carbonyl consisted of a one-pot consists of a two-step process, both catalyzed by a secondary amine organocatalyst: stoichiometric reduction of an aldehyde with IBX followed by addition of an activated alkyl nucleophile to the beta-position of the resulting enal.<ref>{{cite journal|last=Zhang|first=Shi-Lei|coauthors=Xie, He-Xin; Zhu, Jin; Li, Hao; Zhang, Xin-Shuai; Li, Jian; Wang, Wei|title=Organocatalytic enantioselective β-functionalization of aldehydes by oxidation of enamines and their application in cascade reactions|journal=Nature Communications|date=1 March 2011|volume=2|pages=211|doi=10.1038/ncomms1214}}</ref> MacMillan's transformation, which like other photoredox transformations takes place by a radical mechanism, is limited to the addition of highly electrophilic arenes to the same position. The severe limitations on the scope of the arene component in this reaction is due primarily to the need for an arene radical anion which is stable enough not to react directly with enamine or enamine radical cation. In MacMillan's proposed mechanism, the activated photoredox catalyst is quenched oxidatively by an electron-deficient arene, such as 1,4-dicyanobenzene. The photocatalyst then oxidizes transiently generated enamine. The resulting enamine radical cation usually reacts as a 3 π-electron system, but due to the stability of the radical coupling partners, deprotonation of the β-methylene position gives rise to a 5 π-electron system with strong radical character at the newly accessed β-carbon. |
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== References == |
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{{Reflist}} |
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