Cite this:Chem.Soc.Rev .,2011,40,102–113Visible light photoredox catalysis:applications in organic synthesis
Jagan M.R.Narayanam and Corey R.J.Stephenson*
Received 17th March 2010DOI:10.1039/b913880n
The u of visible light nsitization as a means to initiate organic reactions is attractive due to the lack of visible light absorbance by organic compounds,reducing side reactions often
associated with photochemical reactions conducted with high energy UV light.This tutorial review provides a historical overview of visible light photoredox catalysis in organic synthesis along with recent examples which underscore its vast potential to initiate organic transformations.
Introduction
Synthetic organic chemists’pursuit towards new reactions and chemolective transformations under mild and green conditions is a continuous process.Nearly a century ago,Ciamician realized that ‘‘light’’is an abundant and renewable energy source for performing green chemical reactions.1Since then,photochemistry and photocatalysis (via photoinduced-electron-transfer,PET)have found broad utility in organic synthesis.2,3However,the lack of visible light absorption by many organic molecules has limited the application of photo-chemical synthesis.Hence,employing visible light absorbing photocatalysts and utilizing their electron/energy transfer process to nsitize organic molecules to carry out required photochemical reactions would rve as a valuable tool for overcoming this barr
ier.
Nature’s ability to u various visible light absorbing chromophores/photocatalysts for converting solar energy to
chemical energy has inspired various rearch groups to develop a plethora of hosts involving photoredox systems in an effort to mimic natural photosynthesis.4–7The systems have provided a platform to understand and elucidate the electron or energy transfer pathways involved in natural photosynthesis.Among the,photoredox catalysts are of notable importance due to their applications in water splitting,solar energy storage,proton coupled electron transfer,and photovoltaics.8–11In particular,Ru(II )polypyridine complexes are quite interesting due to their ea of synthesis,stability at room temperature,and excellent photoredox properties.Among the complexes,Ru(bpy)3Cl 2,a commercially available complex,is one of the most widely employed photo-catalyst.In this tutorial review,we intend to highlight recent advances and potential applications of photoredox catalysts in organic synthesis.
Photophysical properties of Ru(bpy)32+
Irradiation of Ru(bpy)3Cl 2with visible light (l max =452nm)populates the excited state Ru(bpy)32+*vi
a metal to ligand
Department of Chemistry,Boston University,Boston,Massachutts 02215,USA.E-mail:crjsteph@bu.edu
Jagan M.R.Narayanam
Jagan M.R.Narayanam was born in Peteru (AP),India,in 1979.He received an MSc from the University of Hyderabad in 2001and a PhD in 2008from ETH Zu ¨rich working under the direction of Prof.A.Valla.Since May 2008,he is working as a Swiss National Science Foundation postdoctoral fellow in the group of Prof.Corey Stephenson.His rearch in Stephenson’s group focud on the develop-ment of visible light photo-redox catalysis in organic synthesis and its application in the synthesis of complex natural products.
Corey R.J.Stephenson
Corey R.J.Stephenson was born in Collingwood,Ontario,Canada,in 1974.He received a BSc degree in 1998from the University of Waterloo working with J.Michael Chong,and a PhD in 2004from the University of Pittsburgh working under the direction of Peter Wipf.After carrying out post-doctoral res
earch in the Laboratory of Organic Chemistry at the ETH Zu ¨rich,Switzerland,with Erick M.Carreira,he joined the faculty
at Boston University as an assistant professor of chemistry in 2007.
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charge transfer(MLCT).Relative to the ground state species,
this excited species can be easily oxidized or reduced(Fig.1).
Several oxidative and reductive quenchers of the excited state
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are known and some of them are shown in Fig.1.Oxidative
quenching of Ru(bpy)32+*provides Ru(bpy)33+,a strong
oxidant(1.29V vs.SCE=Standard Calomel Electrode,in
CH3CN),while reductive quenching provides Ru(bpy)3+,a
strong reducing agent(À1.33V vs.SCE in CH3CN).Hence,
depending upon the conditions employed and the
proper lection of the quencher,Ru(bpy)32+*can be utilized
as a single electron oxidant or reductant.
Photoredox catalysis in organic synthesis
Despite the excellent photoredox properties and their ea of
preparation from commercially available precursors,tris-
(bipyridine)ruthenium complexes have attracted very little
attention of synthetic organic chemists.In1984,Cano-Yelo
and Deronzier reported one of thefirst examples,demonstrating
a photocatalytic Pschorr reaction for the synthesis of
phenanthrene and substituted phenanthrenes(Scheme1).12
The Pschorr reaction involves an intramolecular arylation
upon reduction of a diazonium salt by a reducing agent,
electrochemical reduction,or simple heating.13The authors
have chon stilbenediazonium ion1to promote the photo-
英语朗读器catalytic Pschorr reaction.Visible light irradiation of1in the
prence of Ru(bpy)32+in acetonitrile produced phenanthrene
carboxylic acid2in quantitative yield.
The propod mechanism of this reaction is outlined in
Scheme2.Excitation of Ru(bpy)32+by visible light generates
Ru(bpy)32+*(Ru(bpy)33+/Ru(bpy)32+*À0.86V vs.SCE)
which transfers an electron to1(E1/2=À0.1V vs.SCE in
CH3CN)to produce aryl radical4.Intramolecular radical
arylation furnishes radical5which undergoes oxidation by
Ru(bpy)33+and subquent deprotonation to give2while
regenerating the catalyst Ru(bpy)32+.
More interestingly,the direct photolysis of1yielded only
10–20%of2.The remainder of the reactant was converted to
the acetamide3,obtained by trapping of the aryl cation with
acetonitrile followed by hydrolysis.The obrvations also
suggest that the intramolecular arylation does not occur via a
cationic pathway.In subquent studies,the authors found
that para substituted aryl diazonium salts can also oxidatively
quench the excited state species Ru(bpy)32+*to provide
Ru(bpy)33+and corresponding aryl radicals,which are
reduced to arenes.14Inspired by their initial success,
Cano-Yelo and Deronzier extended the application of photo-
redox catalysis to the oxidation of benzylic alcohols to the
corresponding aldehydes(Scheme3).15
Visible light irradiation of benzylic alcohol6in the prence
of RuL32+,8,and collidine in acetonitrile provided the Fig.1General photoredox paradigm of Ru(bpy)3Cl2.
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aldehyde 7in quantitative yield.The yield of the aldehyde decread as the half-wave oxidation potential of alcohol incread.On the other hand,addition of excess ba improved the yield of aldehyde (yield of 9improved from 61%to 90%by addition of 3additional equiv.of collidine).In the abnce of collidine,the yield of aldehyde was markedly decread (30%of 7and o 10%of 9formed from their corresponding alcohols).In all of the reported reactions,a 3:1ratio of benzophenone and fluorenone were formed as byproducts.
In accordance with their obrvations,the authors propod a mechanism initiated by quenching of Ru(bpy)32+*by the aryldiazonium ion 8to generate Ru(bpy)33+and aryl radical 13.Although the authors did not provide a clear mechanism for the oxidation of alcohol to aldehyde,presumably the first step might be the donation of a single electron to Ru(bpy)33+from benzylic alcohol 16to form the radical cation 18while regenerating Ru(bpy)32+.Hydrogen atom abstraction by 13from the radical cation 18followed by deprotonation gives the aldehyde 17(Scheme 4).Fluorenone 15was obrved as a byproduct of the previously described Pschorr reaction (e Scheme 4).
Nearly 20years after Deronzier’s first application of photo-redox catalysis for the synthesis of organic compounds,Zen and co-workers reported the lective and efficient photo-catalytic oxidation of sulfides to sulfoxides.16For this
oxidation,a Nafion membrane doped with a lead ruthenate pyrochlore (Pyc)catalyst and Ru(bpy)32+(designated as |NPyc x –Ru(bpy)|)was ud.Irradiation of the sulfide 20with visible light in the prence of |NPyc x –Ru(bpy)|in CH 3CN/H 2O and continuous purging with O 2for 3h afforded the sulfoxide 21in 97%yield (Scheme 5).It is important to note that no over oxidation of the sulfoxide to the corresponding sulfone,a common problem in classical approaches,was obrved.This photocatalytic oxidation reaction is highlighted by its high sulfoxide lectivity,environmentally benign reagents,ea of purification,and excellent yields.
A propod reaction mechanism is shown in Scheme 5,where Pyc plays a dual catalytic role as the reducing agent in the oxygen reduction reaction (ORR)to produce H 2O 2and also as an electron acceptor from the excited Ru(bpy)32+*to form Ru(bpy)33+.Hydrogen peroxide generated in situ oxidizes the sulfide to sulfoxide while regenerating Ru(bpy)32+.
All of the examples highlighted thus far have dealt with the oxidative quenching of Ru(bpy)32+*to Ru(bpy)33+and utilization of its high oxidation potential for chemical trans-formations.Fukuzumi and co-workers demonstrated the reduction of phenacylbromides using dihydroacridines and Ru(bpy)32+,either in the prence or abnce of acid.17During the studies,Fukuzumi and co-workers demonstrated the modulation of the excited state quenching mechanism by varying the con
centration of Brønsted acid.Although the same product is formed in both cas,in the abnce of acid,the reaction proceeds via reductive quenching of Ru(bpy)32+*to Ru(bpy)3+(Scheme 6,Path A),while at high acid concentration,the reaction proceeds via oxidative quenching
Scheme 5Photocatalytic oxidation of sulfides to sulfoxides.Scheme 6Reductive dehalogenation of phenacyl halides.
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of Ru(bpy)32+*to Ru(bpy)33+since Acr-H2is propod to be
protonated(Scheme6,Path B).The results further display
the ability of modulating the reactivity of photoredox
complexes by varying the reaction conditions.
Subquently,the reductive quenching pathway was utilized
by Okada,Oda and co-workers for the decarboxylation of
acyloxyphthalimides to generate alkyl radicals(Scheme7).可怜的拼音
Visible light irradiation of acyloxyphthalimide25in the
prence of Ru(bpy)32+and BNAH(1-benzyl-1,4-dihydro-
nicotinamide)in aqueous THF furnished the alkyl radical26
which was trapped by a a,b-unsaturated ketone or ester to
produce27and28,respectively,through C–C bond
formation.18Delighted with this success,the authors have
further expanded the scope of the reaction to form C–H19
and C–Se20,21bonds.U of t BuSH in the reaction gave the
alkane29,whereas the reaction in the prence of PhSeSePh
furnished the phenyllenyl ether30.
The propod mechanism depicted in Scheme8begins with
single electron transfer to the visible light excited Ru(bpy)32+*
from BNAH to provide the strong reductant Ru(bpy)3+and
BNAH radical cation,which further decompos to BNA
radical and a proton.The single electron reduction of
acyloxyphthalimide either by Ru(bpy)3+or BNA radical
provides the radical anion31.Protonation generates the
radical32and removal of CO2and phthalimide provides the
alkyl radical26,which could be trapped by radical acceptors
to form C–C,C–H and C–Se bonds.
In2006,Hagawa and co-workers reported the photo-
catalytic reductive opening of C a–O bond of ketoepoxides to
afford b-hydroxy ketones.22In this report,the authors ud
N,N-dimethylbenzimidazolines(Scheme9,35or36)as
sacrificial electron and hydrogen atom donors.The low
oxidation potentials of ADMBI35(+0.28V vs.SCE)and
HPDMBI36(+0.30V vs.SCE)suggest that the reaction is
occurring via reductive quenching of Ru(bpy)32+*to Ru(bpy)3+.
Protonation of the ketone enables single electron transfer from
Ru(bpy)3+to the p*of carbonyl of33.Subquent opening of
epoxide and hydrogen atom abstraction afforded the obrved
b-hydroxy ketone34.Although the yields and conversion are
moderate,this reaction rved to demonstrate the potential of
Ru(bpy)3+as a uful reducing agent.
In2008,Yoon and co-workers reported the photoredox-
mediated highly diastereolective[2+2]cycloaddition of
enones.23Pioneering studies by Bauld and Krische demon-
strated that bis-enones could undergo copper-and cobalt-
mediated single electron transfer initiated formal[2+2]
cycloaddition reactions.24–26
Formation of[2+2]cycloadducts under electrochemical
conditions also supported the intermediacy of radical anion
intermediates.27,28This inspired Yoon and co-workers to
speculate that the formation of a similar radical anion could
be feasible by using Ru(bpy)3+intermediates generated using
visible light irradiation and reductive quenching of
Ru(bpy)32+*by an electron donor.Irradiation of an aryl
dienone37with visible light in the prence of Ru(bpy)32+,
i Pr
2
NEt,and LiBF4in acetonitrile gave the desired intra-
molecular formal[2+2]cycloaddition product38in89%
yield with a>10:1diastereomeric ratio(Scheme10).A
current limitation to this methodology is that one of the
cycloaddition partners for this reaction must be an aryl enone
to initiate the single electron reduction to form the required
radical anion.Aryl enones bearing both electron-withdrawing
or-donating groups and a variety of a,b-unsaturated carbonyl
compounds were shown to be suitable partners for this
reaction.In all the intramolecular cycloadditions reported,
the cis-cyclobutanes were obtained preferentially.This
reaction also facilitates the formation of quaternary centers
in the ca of a-substituted enones.In contrast,intermolecular
cycloaddition reaction of aryl enones provided the homo-
dimerization products(45and46)in very good yields and
high diastereomeric ratio(dr).Unlike intramolecular D
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reactions,this reaction provided all trans -cyclobutanes (meso -isomers)in preference to all cis .However,as mentioned above,this reaction is limited to only aryl enones and no reaction was obrved in the ca of alkyl enones.Omission of any of the reagents,including light,resulted in no obrved [2+2]cycloaddition product 38.In addition,the abnce of product formation without the addition of i Pr 2NEt suggests that the cycloaddition is not initiated by electron transfer from the photoexcited Ru(bpy)32+*to the enone,rather it is initiated by Ru(bpy)3+that is generated by the reductive quenching of Ru(bpy)32+*by i Pr 2NEt.Also,no reaction occurred in the abnce of LiBF 4,a result which has been
attributed to its Lewis acidic nature and ability to improve the solubility of Ru(bpy)3Cl 2in acetonitrile.On the basis of the obrvations,the authors propod the mechanism shown in Scheme 11.
The authors propod that excitation of Ru(bpy)32+by visible light generates the photoexcited state Ru(bpy)32+*,which is followed by single electron transfer from i Pr 2NEt forming Ru(bpy)3+,a strong reductant (À1.33V vs.SCE).A single electron reduction of lithium coordinated enone 49produces the radical 51,eventually leading to the cyclobutane product 48.Presumably,a 1,4-addition of radical 50to another molecule of 49(for intramolecular,another enone or a ,b -unsaturated carbonyl),followed by r
adical cyclization,furnishes the cyclobutane radical 52.Oxidation of 52can be achieved either by excited Ru(bpy)32+*or by the i Pr 2NEt radical cation and produces the cyclobutane 48along with Ru(bpy)3+or i Pr 2NEt.29
Expanding upon the intermolecular homo-dimerization of aryl enones (e 45and 46in Scheme 10),Du and Yoon reported crosd intermolecular formal [2+2]cyclo-additions.30Similar to the intramolecular cycloadditions,one of the reaction partners must be an aryl enone.To overcome the major undesired pathway of homodimerization of the aryl enone,the authors strategically lected more reactive Michael acceptors as the cond reaction partner (Scheme 12).
A mixture of methyl vinyl ketone 54and aryl enone 53(2.5:1),Ru(bpy)32+(5mol%),i Pr 2NEt,and LiBF 4was subjected to visible light irradiation for 4h and provided the crosd [2+2]cycloadduct 55(84%,>10:1dr)in a highly chemolective fashion.Only trace amounts of homo-coupled product derived from 53were obrved.Both electron-rich and -poor substrates are compatible under the conditions.Variation of the substituents at the b -position was possible;
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