Chemistry of First-Row Transition Metal Photocatalysts
David Kornfilt
MacMillan Group Meeting10/17/2018
Introduction
� Triplet Sensitizationwith chromium
� Ligand-directed photochemistry with copper
� Direct photo-HAT with iron
Cr Fe Cu
Why should we care about first-row transition metal photocatalysts?
Properties of Organometallic Photocatalysts
Wenger, O. Chem. Eur. J. 2018, 24, 2039
� Long lived phosphorescent T1 state
� Tunable oxidation and reduction potential
� Singlet ground state
� Highly optimized for SET
� Weak fluorescence, usually TADF
� Ligand dependent absorption spectra
� Singlet or higher spin ground states
� Can do SET and other chemistry
NIr
N
NCr N
NMe
N
NMe
N
N
NMe
N
NMe
N
2nd and 3rd row TM Photocatalysts First row transition metal photocatalysts
Introduction
� Triplet Sensitizationwith chromium
� Ligand-directed photochemistry with copper
� Direct photo-HAT with iron
Cr Fe Cu
Why should we care about first-row transition metal photocatalysts?
Chromium-Based Photocatalysts
Heinze, K., Angew. Chem. Int. Ed., 2015, 54, 11572
Cr N
NMe
N
NMe
N
N
NMe
N
NMe
N
4A2 ground statet2g
3
(t2g)2(eg)1 4T2
ISC 2T22T12E435 nm 500 nm
775 nm
�Quartet ground state (3 unpaired electrons)
�High photon absorption, Φ = 12.1% (Cr[bpy]3+, Φ = 0.09%)
�Long-lived lifetimes of 899, 898, 1164 μs (Cr[bpy]3+, 63 μs)
Oxygen Sensitization with Organic Dyes
3O2
light
photosensitizer
1O2
O
O
O
ClCl
Cl
Cl I
OHII
I
HO
Rose bengal
Spin statistics suggest that TTA produces an overall singlet state only 11% of the time (exclusions apply)
� Singlet Oxygen Production
Photobleaching of photosensitizer can be problematic
3D 3A3D 1A
1D 1A
pentet
triplet
singlet
*
*
*
Heinze, K., Angew. Chem. Int. Ed., 2015, 54, 11572
Oxygen Sensitization with Chromium
Quartet ground state carries away spin, so 4 out of 6 microstates lead to singlets
6-fold increase in collision efficiency
2D 3A
2D 1A
quartet
doublet
*
*
Heinze, K., Angew. Chem. Int. Ed. 2015, 54, 11572
Cr N
NMe
N
NMe
N
N
NMe
N
NMe
N
ISC 2T22T12E
775 nm
Excited state doublet
Amine α-cyanation with Cr
Opatz, T. ChemPhotoChem, 2017, 1, 344
Cr N
NMe
N
NMe
N
N
NMe
N
NMe
NR N
R
R O2, TMSCN 462 nm lightMeCN, 6 h
[Cr(ddpd)2](BF4)3 (1 mol %)R N
R
R
5 examples
CN
N
CN
Me N
CN
Me
Me
47 % yield99% yield
N Pr
Pr
Me
CN
99% yield
NNC
O
O
OH
Ph
63% yield
Radical Cation [4+2] with Chromium Photocatalysts
Ferreira, E. M. Angew. Chem. Int. Ed. 2015, 54, 6506
Me
MeO
Me Cr(Ph2phen)3(BF4)3 (1 mol %)
300-420 nm lightCH3NO2, air,
Ar
Me Me
N N
Ph Ph
Ph2Phen
Ar
EtO2C
Me
Reversed regioselectivity with respect to Diels Alder!
Φ = 0.21in degassed solvent
MeOTs
PMP
Me MeOMe
Me Me
OTBS
Me
PMPC6H13
Me
PMP
Me
Me
Me
PMP
Me
C6H13
89% yield15:1 endo/exo
86% yield19:1 d.r.
74% yield6:1 endo:exo
96% yield 76% yield 78% yield23W CFL, 50% yield
Radical Cation [4+2] with Chromium Photocatalysts
Shores, M. P. J. Am. Chem. Soc. 2016, 138, 5451
CO2Et
MeO
Me Cr(Ph2phen)3(BF4)3
CH3NO2, air, 23W CFL Ar
EtO2C Me
N NAr
EtO2C Me
Ar
HO2C Me
Ar
OHC Me
Ar
EtO2C Me
CH2OAc
75% yield19:1 r.r.
78% yield 6:1 r.r.
Ph Ph
Ph2Phen57% yield 17:1 r.r.
53% yield11:1 r.r.
Ar
EtO2C
Me
Reversed regioselectivity with respect to Diels Alder!
Ar
Ph(O)COAc
Ar
Ph(O)CO
MeMe
61% yield 7:1 r.r.
72% yield 7:1 r.r.
Φ = 0.21in degassed solvent
Oxygen Sensitization for [4+2] Cycloadditions
Shores, M. P. J. Am. Chem. Soc. 2016,138, 5451
LnCr3+*
LnCr3+
1O2
3O2 O2-
LnCr3+ LnCr3+*
LnCr2+
MeAr
MeAr
SET
Me
Me
Ar
Me
Me
Ar
Me
dienophile
diene[4+2] adduct
ET SET
� Double photon mechanism
Energy transfer and electron transfer from same photocatalyst
Formation of Radical Cation Intermediate
CO2Et
MeO
Me Cr(Ph2phen)3(BF4)3
2.00 eV 1.98 eV
CO2Et
MeO1.33 eV vs. SCE
Me Cr(Ph2phen)3(BF4)3
Ph(O)C
Ar Me
CO2Et
MeO
Me hv Me
Ar
Ph(O)C
Ph(O)C C(O)Ph
PMP PMP
1.40 eV
1.66 eV
CO2Et
MeO
Me
Possible Alternative Oxidations
Cr Me
Ar
Ph(O)C
Cr
hv
530 nm LED
Shores, M. P. J. Am. Chem. Soc. 2016, 138, 5451
Convergent Reactivity
PMP
Ph(O)C
Me23W CFL, airCH3NO2, 10 h
67% yieldMe
Me
MePh(O)C
PMP
MePh(O)C
PMP Me
not detected
Ph(O)C C(O)Ph
PMP PMP 23W CFL, airCH3NO2, 6 h PMP
Ph
O
16% yield
MePh(O)C
PMP
Me20% yield
� Cyclobutane A is competent
� Cyclobutane B is competent
Cr Cr
Cr Cr
A
B
Shores, M. P. J. Am. Chem. Soc. 2016, 138, 5451
All roads lead to Rome!
Introduction
� Triplet Sensitizationwith chromium
� Ligand-directed photochemistry with copper
� Direct photo-HAT with iron
Cr Fe Cu
Why should we care about first-row transition metal photocatalysts?
Ligand Substitution on Organometallic Photocatalysts
Wenger, O. Chem. Eur. J. 2018, 24, 2039
� Ir,Ru tris-complexes are usually inert to ligand exchange
� Ligand exchange is usually through two-point binding
� LMCT, MLCT bands interrupted by substitution
� Cu substitution is facile
� Ligand-Metal complex can be directly excited
NIr
N
N
NN
NN
RuN
N
N
N
N
N
N
N
Ir(ppy)3 Ru(bpz)3
NN Cu
LiCuCz2
N
NCu
PMP
PMP
Cl
Cu(dap)Cl
Ligand Directed Cu Photocatalysts
Han, S. B. Org. Lett. 2014, 16, 1310Reiser, O. Angew. Chem. Int. Ed. 2015, 127, 6999
F3CS
Cl
OO
F3CS
ONa
O
Langlois Reagentsource of CF3 radical
ATRA reagentfor CF3 and Cl transfer
RCF3SO2Cl
RCF3
Cl
Me
Cu(dap)2Cl
CF3SO2ClBlue LEDs Me
SO2ClCF3
N NPMP PMP
Ligation to photoactive metal center can directly affect radical stability
Ru
� Trifluoromethylchlorination
� Trifluoromethylsulfonylation
dap ligand
Trifluoromethylchlorosulfonylation with Copper
Me
L2CuCl (1 mol %)
K2HPO4, CF3SO2Cl530nm LED, MeCN, 24 h Me
SO2ClCF3
N NPMP PMP
SO2ClCF3
CF3
SO2ClMeO
SO2ClCF35
CF3
SO2Cl
67 % yield7:3 rr ratio
76% yield
71% yield
56% yield
No Lewis Basic donors
OCF3
Cl
57% yield
Cl
Cl
N
O
O
Cl CF3
53% yield
Lewis basic donors
Reiser, O. Angew. Chem. Int. Ed. 2015, 127, 6999
Ligand-Directed Photocatalysis with Copper
Reiser, O. J. Org. Chem. 2016, 81, 7139
HOOMe
SO
F3C
OO
OMe
SO
F3C
OO
OOH
NHtBu
HOS
F3C
OOO
��Sultone formation is rare
� SO2Cl moiety tolerates alcohols
SO
F3C
OO Me
MeS
O
F3C
OO S
O
F3C
OO S
O
F3C
OO
73% yield 74% yield
H
H
90% yield1.1:1 d.r. 67% yield
*
Cu
530 nm LED
Cu
530 nm LEDβ-blocker derivative
Ligand Excitation of Copper Complexes
CuCl
Non-absorptive
NLi
NN Cu
Absorbs at short and long UVCompetent intermediate for cross-coupling
I CuI (10 mol %), CzLi
CFL or Hg lamp, 10 h
NHAr� Light necessary for reaction
��Amine deprotonation requires base
��Yield increased with Hg lamp
� Radical pathway65 % yield
Formation of UV-active Cu Complexes
Fu, G. Science, 2012, 338, 647
Photoinduced Ullmann Couplings
N-Arylation of Heteroarenes
MeCN, rt, 10h
40% yield
N
Fu, G. Science, 2012, 338, 647
NPh
CuPPh3
PPh3
PhBr, 13W CFL
254 nm lightMeCN, rt, 10h
56% yield
10% CuI, LiOtBuNH
N
Br
� Catalytic copper can be used
Photoinduced Ullmann Couplings
Fu, G. J. Am. Chem. Soc. 2014, 136, 2162Fu, G. Science, 2012, 338, 647
254 nm lightMeCN, rt, 10h
56% yield
10% CuI, LiOtBuNH
N
Br
� Catalytic Ullmann couplings
OH SH
NH2
O
� Nucleophiles
Br Cl
I
� Electrophile
BrC N
Copper Arylation with UV Light
Fu, G. J. Am. Chem. Soc. 2013, 135, 13107
NN Cu
Cu NR2R2N*
Cl
CNCu NR2R2N
CN
Cu NR2X
Cz
CN
CzHLiOtBu
C-N productLiCl
SET
Aryl halide
LiCl
CopperPhotocatalytic
Cycle
Cu
UV light mediated C-N coupling
254-365 nmlight
Mechanistic Investigation of CuCz System
Fu, G. J. Am. Chem. Soc. 2017 139 12716
� Copper carbazolide system selected for further study
Me
Br
LiCz (1.5 equiv)Cz2CuLi (5 mol %)
100W Hg LampMeCN, 8 h, 0 oC
Me
Cz
64% yield
Me
Br 100W Hg LampMeCN, 8 h, 0 oC
Me
Cz
96% yield
Cz2CuILi
catalytic
stoichiometric
� 5% product obtained in absence of copper
� Yield increases over time
What is the source of this background reactivity ?
Cz2CuLi is quenched by alkyl bromide
� kq = 4.8 x 106 M-1 s-1
� t1/2, Cu = 910 ns
Mechanistic Investigation of CuCz System
Fu, G. J. Am. Chem. Soc. 2017 139 12716
LiCz also quenches alkyl bromide!
� kq = 4.9 x 108 M-1 s-1
� t1/2, CzLi = 31 ns
What is the source of this background reactivity ?
Mechanistic Investigation of CuCz System
Fu, G. J. Am. Chem. Soc. 2017 139 12716
Cz2CuLi is quenched by alkyl bromide
� kq = 4.8 x 106 M-1 s-1
� t1/2, Cu = 910 ns
� Alternative catalytic cycle
N
LiCuICz2 LiCuIICz3
Cz
LiCuIICz3 functions as a persistent radical
Br
LiCz*
SET
LiCz
Mechanistic Investigation of CuCz System
Fu, G. J. Am. Chem. Soc. 2017 139 12716
In photocatalysis with 1st row transition metals, multiple pathways are possible!
� Off-cycle reactivity observed as concentration of key LiCuCz3 builds up
Formation and change in absorption due to LiCuCz3 Ratio of Product/dimer increases over time
Mechanistic Investigation of CuCz System
Fu, G. J. Am. Chem. Soc. 2017 139 12716
Traditional SET with Copper Catalysts
Photoactive Ligands
� Formation of photoactive copper catalysts
CuX
Nu
Cu
Photoactive Cu Complex
� Substrate generality
� Wavelength modulation
� Catalyst Stability
OHOH
O
Me Me
PPh2PPh2
PPh NH
tBu
tBu
P(iPr)2
P(iPr)2
Traditional SET with Copper Catalysts
OtBu
O
NH2
1 mol % L110 mol % CuBrLiOtBu (3 equiv)
Blue LED, DME, rtOtBu
O
NHCy
Br
81% yield
NH
tBu
tBu
P(iPr)2
P(iPr)2
N
OCl
Et Ph
carbazoleligand (1.2 mol %)
CuCl (1 mol%)LiOtBu, blue LEDtoluene, -40 oC
N
ON
Et Ph
90% yield94% ee
PPh
NH2
CuI (5 mol%)BINOL (10 mol %)
BTPP, blue LEDMeCN/DMF, -10 oC, 24 h
I HN
Cy
92% yield
OHOH
Fu, G. J. Am. Chem. Soc. 2017, 139, 17707
Fu, G. Science 2016, 351, 681
Fu, G. J. Am. Chem. Soc. 2017, 139, 18101
Introduction
� Triplet Sensitizationwith chromium
� Ligand-directed photochemistry with copper
� Direct photo-HAT with iron
Cr Fe Cu
Why should we care about first-row transition metal photocatalysts?
Direct HAT with Photocatalysts
Wenger, O. S. Chem. Eur. J. 2018, 24 2039
MO
Photo HAT
MO
* H
MOH
+
alkyl radical
Non-Photo HAT
PivO
Fe(PDP) (5 mol %)
AcOH, H2O2, MeCN, 0.5 h, rt PivO
OHMeMe White, 2007
51% yield
Mn(TMP)Cl (1 mol%)
NaOCl, TBAClDCM, 12 h, rt
Cl51 yield4:1 r.r.
Groves, 2015
Direct HAT with Photocatalysts
� ~390 nm excitation
� Powerful oxygen centered abstractor
� Selective C-H abstraction
� Electronic properties not tunable
� ~420 nm Soret band
� Powerful oxygen centered abstractor
� Selective C-H abstraction
� Electronic properties highly tunable
� Short-lived photoexcited state!
WO
O
OW
W
OO
WO
O
O
OW
O
O
O
O
O
W
W
OO
WO
O
O
OW
O
O
O
WO
O
O
O
O
O
O
O
4–
O
Fagnoni, M. Acc. Chem. Res. 2016, 49, 2232Emily Scott Lab Webpage, umich.edu
Iron Photosensitizers for HAT
NN N
NFeIII
O
N
N NN
FeIII
C6F5
C6F5
C6F5 O C6F5
C6F5
C6F5
Pacman-Complex
Pacman (0.0007 mol%)Me
1 M in pyridine
Me
425 nm lightO2 (1 atm), 18 h
76 TONΦp =0.00151
425 nm light
NN N
NFeIV
O
N
N NN
FeII
C6F5
C6F5
C6F5O
C6F5
C6F5
C6F5
Active oxidation complex
reclamp
� Sole observed product
� Competitive reclamping
� KH/KD = 1.55
Light-driven HAT from Toluene
Nocera, D. G. J. Am. Chem. Soc. 2006, 128, 6546
Iron Photosensitizers for HAT
Me
287 TONΦp =0.0152
235 TONΦp = ND
160 TONΦp =0.00276
143 TONΦp =0.00199
H H H
HAT from weak C-H bonds
NN N
NFeIII
O
N
N NN
FeIII
C6F5
C6F5
C6F5 O C6F5
C6F5
C6F5
Pacman-Complex
425 nm light
NN N
NFeIV
O
N
N NN
FeII
C6F5
C6F5
C6F5O
C6F5
C6F5
C6F5
Active oxidation complex
reclamp
Nocera, D. G. J. Am. Chem. Soc. 2006, 128, 6546
Iron Photosensitizers for HAT
Fe FeO
Fe FeO
Me
Fe FeOH
OH
Fe Fe
O2
� Radical rebound
� No backgroud reaction
� Reclamp t1/2 = 2.3 ns
� KH/KD > 1 suggests PCET
Substrate
Product
Photocatalytic Fe H Atom Abstraction
Fe
Iron Photocatalytic
Cycle
Nocera, D. G. J. Am. Chem. Soc. 2006, 128, 6546
Introduction
� Triplet Sensitizationwith chromium
� Ligand-directed photochemistry with copper
� Direct photo-HAT with iron
Cr Fe Cu
Why should we care about first-row transition metal photocatalysts?
First row transition metal catalysts enable new photochemistry!
Introduction
� Triplet Sensitizationwith chromium
� Ligand-directed photochemistry with copper
� Direct photo-HAT with iron
Cr Fe Cu
Why should we care about first-row transition metal photocatalysts?
First row transition metal catalysts enable new photochemistry!