2010/05/12 (Wed)Noriaki Takasu (D1)

Literature Seminar (D1 Part)

Photoredox Catalyst in Organic Chemistry~Toward Green & Efficient Reaction~

Ru(bpy)32+Ir(ppy)2(dtb-bpy)+

Photochemical reaction has a large potential in green chemistry. In various areas, photochemicalenergy was used. Nature's ability to convert solar energy to chemical energy in photosynthesis
has inspired the development of a host of photoredox systems in efforts to mimic this process.
Today's theme "Photoredox Catalyst" is discovery and development with a lot of potential of suchNature-mimic system in all area of science, including organic chemistry.

Contents
1. Introduction -Photochemistry- (P.2)
2. Photoredox Catalyst (P.3-4)
3. Photoredox Catalyst in Organic Reaction
3-1. Early Important Report (MacMillan's Work) (P.5-7)
3-2. Various Reactions Using Photoredox Catalyst (P.8-9)
3-3. Reaction Using Ir Catalyst (P.10-11)
4. Other Catalysts (Other Recent Applications) (P.12)
5. Summary & Future (P.13)

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1. Introduction -PhotochemistryPhotocatalyst(ref. Itano's Lit. (M2 Part))

Inorganic Photocatalyst

Organic Photocatalyst (Sensitizer)

Photocatalyst is applied to many fields;
antibacterial, sterilization, deodorization, antifouling,antifogging, water / air purification...

Most of photo reactions of organic compound undergo inTriplet Excited State.

TiO2 is employed in most area.

Organic
Compoundh(UV)(Semiconductor)

Singlet Excited State

Triplet Sensitizer

Figure. Photocatalysis Principle of TiO2
hTriplet Excited State

electronconductive bande-Figure. Example of Triplet Sensitizer

bandgap forbidden
bandenergyExamples;VariousEffectO

valence bandOBenzophenone (BP)positiveholeO
Anthraquinone (AQ)
Ovalence electron excitation by photo energy(Light Souce : UltraViolet (< 400 nm))Cl

Other Application : water splitting
conversion of CO2 into hydrocarbon

ClCl
NO25-Nitroacenaphthen (NAN)So Important Tool in Our Life

Photo Reaction (Photochemistry in Organic Reaction)

ClO
ChloranilChem. Rev., 2007, 107, 2725.
Chem. Rev., 2008, 108, 1052.

Scheme. Example of Photo Reaction[2+2] Photocycloaddition

Electron-Transfer Reaction

Intermolecular Addition onto Unsaturated C-C Bond

These reactions' "reagent" is light source. These are high atom economy and green reaction.
But, Most light source is ultraviolet, which is reactive for unsaturated bond and some functional group, and is not
Nature's light.

=
Visible light
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2. Photoredox Catalyst
Catalyst that shows oxidative and reductive property by absorbing visible-photoenergy
Most of photoredox catalyst is metal-ligand complex molecules.
Metal : Ru, Ir, Cr, Rh, Co...
Ligand : 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen)...
Among them, Ru(bpy)32+ is most studied one-electron photoredox catalyst.

2-1. Photophysical Property of Ru(bpy)32+ K. Kalyanasundaram, Coord. Chem. Rev., 1982, 46, 159.
A. Julis et al., Coord. Chem. Rev., 1988, 84, 85.

Photoabsorption and Excited StateRu(bpy)32+hMLCT

Ru(bpy)32+*
excited state=
Metal-to-Ligand Charge Transfer

2+ charge of Ruthenium is transferred to Ligand (trisbipyridine) byphotoenergy. so high energy state, triplet excited state.

Figure. Absorption and emission spectrum for Ru(bpy)32+ in aqueous solution
at room temperature along with the assignments for the various bands.
Absorption

MLCT absorption bandEmission

MLCT excited state absorption;
max= 452 nm

Visible Light

By irradiated with visible light,Ru(bpy)32+ is excited high energy state.
Excited state energy was computed;
E 0[Ru(bpy)32+/2+*] = -2.10 V(vs. SCE in MeCN)

Energetics of Various Redox State

A.J. Bard et al., JACS, 1973, 95, 6582.

T able. Oxidation and Reduction Potential evaluated by Cyclic Voltammetry.

Ox + eRe , E(V)E > 0 : potent oxidant
E < 0 : potent reductant+2 state : stable ground state;+3 state : good oxidant+1 state : good reductantcf) oxidising water to O2 (E0(O2/H2O) = +1.23 V

SCE : Saturated Calomel Electrodea reference electrode based on the reaction between
elemental mercury and mercury(I) chloride in KCl sat. aq.;use mesurement of Redox potential

NHE : Normal Hydrogen Electrode (= SHE)a redox electrode which forms the basis of thethermodynamics scale of oxidation - reduction potentials;
use mesurement of Redox potential

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The excited state redox potentials are obtainable from the redox potentials of the corresponding ground state.
(Probably, the excited state energy is all available as free energy for the excited state redox processes.)
C. Creutz, N. Sutin, Inorg. Chem., 1976, 15, 496
T. J. Meyer et al., JACS, 1979, 101, 4815

Calculated (vs. SCE);

Figure. Redox potential diaglam- 2.10 + 1.29 = - 0.81 V

reductantoxidantoxidant

reductant- 1.33 - (-2.12) = + 0.77 V
Table. Formal Reduction Potentials at Room Temperature ( = 0.1 M)

potent oxidant
potent reductant
Excited state Ru(bpy)32+* is good oxidant and good reductant

Redox Quenching of excited state

Table. Rate parameters in the quenching of Ru(bpy)32+* byinorganic ions and molecules (kq ; quenching rate constant,
k2 :decrease rate constant of Ru(bpy)32+* )generation of singlet oxigen

Several Application (Using Visible Light)
Water split

Reduction of Carbon DioxideRu(bpy)32+ + CO2

H2 & O2 Productionh (400 nm)
N(CH2CH2OH)3-DMF

HCO2H

CO2 + 2H+ + 2e- HCO2H E = -0.61 V
Ru(bpy)3Cl2
photosensitizerh (400 nm)

Ru(bpy)32+*protonsourceRu(bpy)32+* + N(CH2CH2OH)3
Ru(bpy)3+ + N(CH2CH2OH)3
reductant
proton source 1/2 HCO2HRu(bpy)3+ + 1/2 CO2Ru(bpy)32+

G. Christou et al., J. Chem. Soc., Chem. Comm., 1985, 56. 4/13

3. Photoredox Catalyst in Organic Reaction
3-1. Early Important Report (MacMillan's Work)
Background and Consideration
Many fundamental organic reactions rely on thegeneration and use of radicals or singleelectron intermediates; metal-mediatedreaction, photoreaction, polymerization, etc...

Ru(bpy)32+ : one-electron photoredox
catalyst, important development of H2,
O2, energy storage, etc...

Application as initiator ofsingle-electron intermediates??
On the other hand....
Previous MacMillan's work : organo-HOMO, LUMO, SOMO-activation catalysis (ref. Mihara's Lit. (D1 Part))
D. W. C. MacMillan et al., Science, 2007, 316, 582.
= Single Occupied Molecular Orbital

SET (Single Electron Transfer)=One-Electron Oxidation

O
O
5H

Mealdehyde+

MeSiMe3N+N
H

Ph

allylsilaneOMe

20 mol% catalyst

5CAN (2.0 eq)

H

NaHCO3, 24 h
DME, -20°C
88%, 91% eeMeProductIn later report...
Many Applications of SOMO catalysis via SET;
Aldol, Friedel-Crafts, Vinylation, Allylation,Arylation, Enolation, Enal Reduction, ....

Me

JACS, 2007, 129, 7004.
JACS, 2008, 130, 16494.
JACS, 2009, 131, 11332.
JACS, 2010, 132, 5027.

O
N

R1

See these literature;

Me

JACS, 2008, 130, 398.
JACS, 2009, 131, 11640.
ACIE, 2009, 48, 5121.
et cetera...

N
H

In other examples,-allyl aldehyde was provided
in high yield & enantioselectivity.

MeO
N
HX or
HX R1, R2t21R
R
R2 = Me, Bn, BuN
H

SET Reagent : CAN, Fe complexSuggestion of New Catalytic System
Ru(bpy)32+
Powerful Inorganic
Electron-Transfer
Catalyst+MacMillan's Catalyst
Powerful Organic
Enantioselective
Catalyst

CombineNew
Catalytic System

Enantioselective Reactionin Mild & Green Conditions

Merging photoredox catalysis with organocatalysis

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-Alkylation of Aldehyde Using New Catalytic System

D. W. C. MacMillan et al., Science, 2008, 322, 77.

Proposed Mechanism (Theoretical Hypothesis)
Figure. Merging Photoredox Cataysis with Organocatalyis. Proposed Mechanism.
H2OSOMOphileSOMO

E = -0.92 ~ -1.12 V vs. SCE in MeCN
a low barrier to oxidation
Chem. Phys. Lett., 1986, 131, 189

H2O

E = -1.33 V vs. SCE in MeCN
(potent reductant)
JACS, 1979, 101, 4815

MLCT excited state
potent oxidant or reductant

Phenacyl bromide wasreducted in this reductant.
(Half-reduction potential;
E 1/2 = -4.9 V vs. SCE in MeCN)
J. Phy.Chem, 1990, 94, 722

light(photosensitizer)

MeO

Start of cycle : 2 (MLCT exited state, high energyintermediate) removes a single electron from atrace quantify of enamine (slowly). Generated
radical amine quenched in photoredox cycle.

MeNNt BuMeRu(bpy)32+*2MeON

Nt BuRu(bpy)3+R3R
not participate in reaction

Figure. Ru(bpy)3Cl2 Emission Quenching by Enamine 8
I0 = Emission intensity of Ru(bpy)32+.
I = Emission intensity of Ru(bpy)32+ in the presence of quencher.
Small decrease of emission intensity in presence of enamine.
2 behaves as an oxidant, and enamine can be reactedwith Ru(bpy)32+ (but so slowly).

Electron-deficient radical 5 is reactive, so it reacts with enamine 8 (fast).
Stereocontrol and reaction surfice control of enamine 8;
R Re face covered Substituent on N is away from vulky tert-butyl group.
NON

To minimize with non-bonding electron pair, (E)-configuration.
Methyl group effectively shields the Re face.
Enantioselective radical addition from Si face

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ResultOO+R(2 eq.)

OX

YOBr
racemicO

CO2Et

ROO

CO2Et

Etb) 86%, 90% ee

CO2EtO

CO2Et

CO2Et

3a) 93%, 90% ee

Ru(bpy)3Cl21MeBuN
0.5mol%6 H HOTf
photoredox
20 mol%catalyst
organocatalystt

CO2Et
CO2EtHexMeNXY

2,6-lutidine, DMF
5 - 16 h, rt

CO2Et

OO

catalyst combination
1&615W fluorescent lightOOCO2EtPhc) 92%, 90% eed) 83%, 95% ee

PhPhPhPh

83% (1:1 mixture)radical clock substrate
OCO2EtPhOMeO

Previous SOMO activation;
MeO

Hex ONHex ONBoce) 66%, 91% eef) 63%, 93% ee

OCy

CO2Et

CO2Et

OOg) 84%, 96% eeMeh) 87%, 96% ee

Nt Bu

active spieces
Enamine is SOMORNO2OOOCH2CF3O Me CO Et
2CO2EtHex O

Hex Oi) 84%, 95% eek) 80%, 92% eeHexl) 80%, 88% ee

cyclopropyl ring opening(not undergo)tBuO2COHex Om) 70%, 5:1 dr, 99% ee

In this reaction systems,enamine is SOMOphile.
(see Proposed Mechanism)

Chemical functionalities that are prone to redox (olefins, esters, carbamates, and arenes) were inert to these mild
redox conditions (b-f). Chemoselective Reaction.
Vulkiness of R has little impact of yield & ee.
Electron-deficient -bromo carbonyls effectively serve as alkylating agents (g-m).
Tertiary bromo-substituted alkylating agents are readily employed (l, m).
A 2g alkylation was readily accomplished (g).
Exclusion of light failed to produce even trace quantities of the coupling adduct.
Removal of Ru(bpy)32+ resulted in small quantities of product (24 h).
Light source tuned to the Ru(bpy)32+ MLCT absorption band resulted in a acceleration (90 min).

Participationof theRu(bpy)32+*
excited state

It does not require any heating or cooling, all of the components are commercially available and inexpensive.
Simple household 15-W fluorescent light bulb can be employed as a suitable light source

Visible Light

Chemoselective Reaction, and Decrease of Side Reaction
diastereoselectivity of m;
RRO

R'NO

R' NNONO

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3-2. Various Reactions Using Photoredox Catalysis
Reductive Dehalogenation

Intramolecular Radical Addition (Tin-Free)

Classical Method
ClN
NH
Br

C. R. J. Stephenson et al., Org. Lett., 2010, 12, 368.
Scheme. Intramolecular Radical Addition of Indole and pyrrole

ClBu3SnH, AIBNN

C6H6, reflux
99%

NHNOrg. Lett., 2005, 7, 2965.

Br CO2Et
CO2Et

Using trialkyltin, toxic and environmental pollutants.

Using Photoredox Catalyst (Tin-Free Method))N

Br CO2Et
CO2Et

C. R. J. Stephenson et al., J. Am. Chem. Soc., 2009, 131, 8756.

Scheme. Reductive Debromination

CO2Me
CO2Me

15W fluorescent light
DMF, rt, 12 h73%

NRu(bpy)3Cl2 (1 mol%)
Et3N (2 eq)

CO2Me
CO2Me

15W fluorescent light
DMF, rt, 12 h
80%

N

Other several examples was performed, in moderate - high yields.

i Pr NEt (10 eq), HCOOH (10 eq) (90%)
2BrRu(bpy)3Cl2 (1 mol%)
Et3N (2 eq)

Hori Pr NEt (2.0 eq), Hantzsh ester (1.1 eq) (95%)
2NHBocNBoc Ru(bpy)3Cl2 (2.5 mol%), 14W fluorescent bulb
DMF, rt, 4 hNHBocNBoc

T able. Reductive Dehalogenation Using Photoredox Catalysis
Single Diastereomer
H

MeO2C
MeO2CHN

H

Various chemical functionalities were inert to these
redox conditions.
Tin-Free, and mild conditions

3 : Hantzsh ester

Scheme. Proposed Mechanism

cyclopropyl (radical clock) : opening ring
OOX

R1R2R1NOONBrHHOOR2Ru* - Amine electron transfer was reported;JACS, 1979,
101, 4007

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[2+2] Cycloaddition (Enone Cycloaddition)
Previous Method (Kirsche)

R = 2-naphtyl
R = phenyl

J. Am. Chem. Soc, 2002, 124, 9448.

0%
12%

90%
43%

Slow addition (60 s) of Me2CuLi (25 mol%) to a solutionof substrate (100 mol%)J. Org. Chem, 2004, 69, 7979.

Problem of these reaction systems; Chemoselectivity, Yield, Narrowness of sabstrate scope
New Method Using Photoredox Catalyst
ORO
R'Ru(bpy)3Cl2 (5 mol%)
iPr2NEt (2.0 eq)
LiBF4 (2.0 eq)
275W floodlight

T. P. Yoon et al., J. Am. Chem. Soc., 2008, 130, 12886.
OOHH

R

Aliphatic enone and enoate do not cyclize (entries 5, 6)
because of more negative reduction potential
R'Table. Visible Light Photocatalysis of Enone Cycloadditiona

RR

e-JACS, 1972, 94, 8471.

OO
E 1/2 (V) vs.SCE : R = Ph > Alkyl

Alloxyno reaction in the absence of i Pr2NEt
Cycloaddition is not directly initiated by Ru(bpy)32+*,Ru(bpy)3+ formed by reductive quenching of amine.
no reaction occurs in the absence of LiBF4
Ru(bpy)3Cl2 : sparingly soluble++Ru(bpy)3(BF4)2 : soluble+Na , Bu4N : low reactivity
Li is involved in reaction.
cf.
E 1/2 = -1.58 V (vs. SCE)
PhPhRu(bpy)3+ : lack of reductive power
H
COPh So, Li+ is essential
Scheme.

gram scale
Scheme. Proposed Mechanism

Yoon, JACS, 2009,
131, 14604

O
Ri

Pr2NEt

OO

e-R

R'O
R

O
R'O
RO
R'O
R'

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3-3. Reaction Using Ir CatalystIr(ppy)2(dtb-bpy)+

S. Bernhard et al., J. Am. Chem. Soc., 2004, 126, 2763.
S. Bernhard et al., J. Am. Chem. Soc., 2004, 126, 14219.
Various Ir photoredox catalyst was synthesized and investigated property;
It readily accepts a photon from a visible light, and excites.
high reductive ability of one-electron oxidative stateIr(ppy)2(dtb-bpy)+
stable ground statevisible light
MLCT

oxidative quenchingIr(ppy)2(dtb-bpy)+

Ir(ppy)2(dtb-bpy)+*
3MLCT excited stateIr(ppy)2(dtb-bpy)
one-electron oxidative state
E = -1.51 V vs. SCE in MeCN

potent powerful reductantAza-Henry Reaction via C-H Activation

C. R. J. Stephenson et al., J. Am. Chem. Soc., 2010, 132, 1464.

Table. Oxidative Iminium Ion Generation and Trapping

Table. Oxidative Aza-Henry Reaction

15W fluorescent lamp, open to air

3: Ru(bpy)3Cl2.

Reactivity : Ru cat. < Ir cat.
Scheme. Plausible Mechanism
open to air.

Although the process was slowly, C-H oxidation of anonbenzylic amine afforded (entry 9).

lack of O2

decrease of reactivity

Although reaction using Cu(I) and TBHP is faster thanthese reactions (ref. JACS, 2005, 127, 3672), thesereactions provide desired products in higher yields.

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-Trifluoromethylation of Aldehyde

D. W. C. MacMillan et al., J. Am. Chem. Soc., 2009, 131, 10875.

Table. Enantioselective -Trifluoromethylation: Initial Studies

Table. Enantioselective -Trifluoromethylation: Aldehyde Scope

Yield of the corresponding alcohol.

Racemization was detected in room temperature,but in low temperature, racemization was not detected.
Reactivity and selectivity : Ru cat. < Ir cat.

Table. Enantioselective -Perfluoroalkylation: Alkyl Iodide Scope
Scheme. Proposed Merger of Catalytic Cycles for CF3-Alkylation

E 1/2 = -1.21 V
vs SCE in DMF

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4. Other Catalysts (Other Recent Applications)
Ru-Pd complex (Dimerization of Methystyrene)

M. Akita et al., Chem. Comm., 2005, 5468.
M. Akita et al., Inorg. Chem., 2007, 46, 2432.

Scheme . Proposed Mechanism
Scheme . Transition-metal complex containing
a visible-light-absorning unit

Solv.: acetone

cat.Ru-Pd

2150W Xe lamp(> 420 nm)
CH3NO2, rt
90%

Figure . Consumption rate of the monomer in thereaction of 9-11 under irradiated conditions.

Cr Complex

J. M. Kelly et al., Dalton Trans., 2010, 3990.

strongly binding and interact with DNA
Phosphorescence of complex is efficiently quenched.

[Cr(phen)2(X2dqqz)]3+

When it binds with DNA, it shows property to photoenergy.

Potential as nucleic acid probes
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5. Summary & Futureconserves energy in absorbing visible light, and functions
development in the field related to the environment.
After that
In organic chemistry, using this catalyst, radical-mediated efficient and green
reaction was developed. However, application examples is still few.

Next study
Development of more efficient catalyst (Metal, Ligand, ...)
Expand of this catalytic system in many fields (In organic reaction, new radical-reaction)

And...
Thess "efficient and chemoselective" methodology represents a potential means for accessinga variety of medicinally and biologically active natural or non-natural products.
Synthesis of Complex Molecules

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