Polyoxometalate Photocatalysis

Thomas Brewer MacMillan Group Meeting December 13, 2017 What are polyoxometalates (POMs)?

Type I Type II Type III monooxo terminal groups cis-dioxo terminal groups monooxo and cis-dioxo terminal groups

6- 6- 10- Ex: [M10O28] (M = Nb, Ta, V) Ex: [W7O24] Ex: [H2W12O42]

≥ 3 transition metal oxyanions linked by shared oxygen atoms

closed, 3-dimensional frameworks typically group 6 (Mo, W) and group 5 (V, Nb, Ta) type I & III POMs shown to be reversibly reduced to “heteropoly blues”

Pope, M. T. Inorg. Chem., 1972, 11, 1973 structures from http://verahill.blogspot.com/search/label/molecules Outline

Polyoxometalate Fundamentals C–H Oxygenation/Fluorination Reactions

1 1 3 S0 S1 T1 h! ISC H X POM 1(O→M LMCT) 3(O→M LMCT)

C–C Bond-Forming Reactions

H R POM synthesis

[H+] n- t- [MO4] [MmOr] H2O isopolyoxometalates only TM and oxide ions

4- Ex: [W10O32]

[H+] n- q- t- [MO4] [XOpHh] [XxMmOr] H O 2 heteropolyoxometalates contain ≧1 ‘heteroatom’

3- Ex: [PMo12O40] (fun fact: discovered in 1826!)

O O O O O O O O via olation: M M M M + H2O HO O HO O O O O

can include heteroatoms “X” to form hetero-POMs frequently involve equilibria between several POMs

controlled by pH, counterion identity, temperature, cosolvent, M/X ratio

Berzelius, J. J. Pogg. Ann. 1826, 6, 380 Weinstock, I. A. Chem. Rev. 1998, 98, 113 Hill, C. L.; McCartha-Prosser, C. M. Catal. Met. Complexes Type I POMs have rich redox chemistry

2a1* + e* np

a1*

ns 2 2 b1* (x -y ) O L L e* (xz, yz) M L L (n-1)d b2 (xy) L !(z) e idealized local symmetry "(xy)

3a1 + b1 + e "(z)

MOL5 MO diagram (C4v, no xy !-bonding)

TM atoms in highest (d0) oxidation state ⇒ POMs act as oxidants

Type I POMs have formally nonbonding LUMO (b2) In type II POMs, former dxy orbital is !*

Polyoxometalate Molecular Science; Almenar-Borras, J. J., Coronado, E., Muller, A., Pope, M., Eds.; Springer: Dordrecht, 2003 POM photoredox reactivity

1 1 3 3 2 S0 S1 T1 (RP) D h! ISC D–H POM 1(O→M LMCT) 3(O→M LMCT) 3(POM– H∙ ∙ ∙D•) 2(POM– H) + 2(D•)

LUMO HOMO

4- 3- 3- 6- 3- [W10O32] [PW12O40] [PMo12O40] [V10O28] [V13O34]

"max 324 nm 263 nm 220 nm 240 nm 202 nm

0,0 transition 450 nm 415 nm 415 nm 490 nm 560 nm ground state reductiona -0.97 V -0.37 V +0.14 V -0.24 Vb +0.63 V excited state reductiona 2.44 V 2.63 V 2.67 V 2.01 V 2.84 V

Potentials are very approximatec V, Mo POMs strong oxidants, but difficult to re-oxidize to d0

V, Mo POMs can be sufficiently oxidizing in ground state to react with oxidizable intermediates POMs typically show long (100s of nm), tailing absorbance

apotential vs. NHE | birreversible reduction | cvarious reference electrodes and experimental conditions; literature not in agreement De Waele, V., Poizat, O., Fagnoni, M., Bagno, A., Ravelli, D. ACS Catal., 2016, 6, 7174 Hou, D., Hagen, K. S., Hill, C. L., J. Am. Chem. Soc., 1992, 114, 5864 Polyoxometalate Molecular Science; Almenar-Borras, J. J., Coronado, E., Muller, A., Pope, M., Eds.; Springer: Dordrecht, 2003 A closer look at decatungstate photochemistry

4- [W10O32] * τ < 1 ps 1 hot 4- ISC S1 [W10O32] * τ ~ 10 ps 1 S1 4- [W10O32] * η ~ 0.5 3 T1 h! η ~ 0.5 D–H τ ~ 50 ns 3 T1 HOMO-1 (A1g)

[W O ]4- 4- 10 32 oxidation [HW10O32] 1 a S0 E½ = -0.97 V

disproportionation

5 -1 -1 4- k = 6 x 10 M s [H2W10O32] a E½ = -1.4 V

3 after excitation, fast (τ ~ 10 ps) ISC yields the reactive T1 state 3 T1 HOMO-1 has highest (accessible) density on apical oxo ligands 4- 4- 4- Singly-reduced [HW10O32] can disproportionate to [W10O32] and [H2W10O32]

apotential vs. SCE De Waele, V., Poizat, O., Fagnoni, M., Bagno, A., Ravelli, D. ACS Catal. 2016, 6, 7174 Yamase, T., Takabayashi, N., Kaji, M. J. Chem. Soc. Dalton Trans. 1984, 793 Decatungstate redox potentials vary widely

e e 4- 5- 6- [W10O32] [W10O32] [W10O32] E½(1) E½(2)

a a MeCN : H2O E½(1) E½(2)

10 : 0 -0.94 -1.37

9 : 1 -0.72 -0.96

8 : 2 -0.62 -0.81

7 : 3 -0.59 -0.74

strongly dependent on solvent strongly dependent on protonation state

a potential vs. Ag/AgCl | protonation-dependent CV potentials vs. Ag/AgNO3 Renneke, R. F., Kadkhodayan, M., Pasquali, M., Hill, C. L. J. Am. Chem. Soc. 1991, 113, 8357 Yamase, T., Takabayashi, N., Kaji, M. J. Chem. Soc. Dalton Trans. 1984, 0, 793 POM photoredox catalysis

Sub Kinetics of POM photoredox POM K

- POM Sub O2 , H2, etc. "K[Sub] R = generalized POM 1 + K[Sub] h! photoredox cycle rate initial

O2, H2O, oxidants POM* Sub [Sub]

12 -1 -1 " ~ 10 M s preassociation POMred shows similar dependence on [POM]

Subox

Common POM photoredox catalysts Selected substrate classes

H O NR2 OH

alkanes ethers amines alcohols

Cl CN Ar R n- 4- [XM12O40] [W10O32] X = P, Si, Fe, H2, etc. alkyl-Cl nitriles alkenes benzylic M = W, Mo

Fox, M. A., Cardona, R., Gaillard, E. J. Am. Chem. Soc. 1987, 109, 6347 Papaconstantinou, E. Chem. Soc. Rev. 1989, 18, 1 Polyoxometalate Molecular Science; Almenar-Borras, J. J., Coronado, E., Muller, A., Pope, M., Eds.; Springer: Dordrecht, 2003 Site selectivity in decatungstate-mediated C–H abstraction

O O

W O W O O OO OO ‡ O O O W O W O + - O h! " " O H O W O O W O H O W O O O W W O O O O O O O O O O W O W O O Polar effects O Me O H H H Me O H O H Me N Me HO Me H H H

19% / 81%a 100%a 100%a 15% / 85%a 7% / 93%a

Me Me O H H H O H NC CN NC H H H N Me

100%a 14% / 86%a 29% / 71%b 9% / 91%a n.r.a

aMichael addition | boxygenation | decatungstate chemdraw provided by Ian Perry Ravelli, D., Fagnoni, M., Fukuyama, T., Nishikawa, T., Ryu, I. ACS Catal. 2017, just accepted Site selectivity in decatungstate-mediated C–H abstraction

O O

W O W O O OO OO ‡ O O O W O W O + - O h! " " O H O W O O W O H O W O O O W W O O O O O O O O O O W O W O O Steric effects

4-* Me [W10O32] O O H Me Me H O H Me t-Bu H Me Me Me Me H Me H Me 4-* Me [W10O32] 30% / 70%a n.r.a 100%a

weak C–H bonds

H Me H O H H O Me H H O H2N H

20% / 80%a 48% / 52%a 100%a 100%a 100%a

aMichael addition | decatungstate chemdraw provided by Ian Perry Ravelli, D., Fagnoni, M., Fukuyama, T., Nishikawa, T., Ryu, I. ACS Catal. 2017, just accepted Outline

Polyoxometalate Fundamentals C–H Oxygenation/Fluorination Reactions

1 1 3 S0 S1 T1 h! ISC H X POM 1(O→M LMCT) 3(O→M LMCT)

C–C Bond-Forming Reactions

H R Early work in decatungstate-catalyzed C–H oxygenation

Me H (Bu4N)4W10O32 (0.4 mol%) Me OOH Me Me Me h!, MeCN, O2 Me 55%, sole product

4- Me H [W12O32] * Me Initiation Me Me Me HAT Me

H Me Me Me O O Me O Me Me OOH Me Propogation O + Me Me Me Me Me Me Me Me

Me Me Me H Me Me O Me Termination Me Me + Me O t-BuOOt-Bu Me Me Me Me Me H Me Me

4- [HW10O32] turned over by O2 Alternative to organic radical intitiators

Chambers, R. C., Hill, C. L. Inorg. Chem. 1989, 28, 2509 Further studies on decatungstate-catalyzed C–H oxygenation

(Bu4N)4W10O32 H OH + O h!, O2

Oxygenative transformations OH O OH O R R R Me Me Me Me

2° alcohol ketone 2° benzylic C–H 2° alcohol aryl ketone

O OH O OH OH

1° benzylic alcohol benzoic acid 2° C–H 2° alcohol ketone

OH Me Me OH Me O

3° C–H 3° alcohol 2° allylic C–H allylic alcohol enone

Tzirakis, M. D., Lykakis, I. N., Orfanopoulos, M. Chem. Soc. Rev., 2009, 38, 2609 Oxyfunctionalization of remote C–H bonds of aliphatic amines

α-amino C–H polarity inversion

R 4- R H R 4- H R [W10O32] H+ [W10O32] N N N N h! h!

most hydridic C–H

Protonation inverts polarity of α-amino C–H bonds ⇒ distal C–H abstraction possible

Distal C–H oxygenation

Na W O (1 mol%) 4 10 32 H H R H H H SO (1.5 equiv.), H O (2.5 equiv.) N HSO4 derivitization N N 2 4 2 2 N or MeCN/H2O, h! O O RN

Uses desirable unprotected aliphatic amines keto-amine substitution pattern common motif in biologically-relevant molecules

amenable to flow (0.7 M, 5 g scale, 5.0 bar O2 as oxidant)

Schultz, D. M., Davies, I. W., et al. Angew. Chem. Int. Ed. 2017, 56, 15274 Oxyfunctionalization of remote C–H bonds of aliphatic amines

Substrate scopea

Boc Boc Boc Et N N N N

O BnO N O O

64% AY 68% AY (2:1 γ:β) 58% AY 46% AY 43% IY 43% IY (γ) 43% IY 33% IY

H NHCBz Me N CO2H H N CO2Me O

BocHN CO2Me N O O OBn 48% AY 53% AY 29% AY 51% AY 26% IY 43% IY 41% IY

H PhHN N N O O

NH2 NH2 Me Me NHBoc Me Me OH 57% AY 60% AY 36% AY (2:1 δ:γ) 64% AY 47% IY 50% IY

aAY = assay yield before derivitization; IY = isolated yield after derivitization Schultz, D. M., Davies, I. W., et al. Angew. Chem. Int. Ed. 2017, 56, 15274 TBADT-catalyzed fluorination of unactivated C–H bonds

H (TBA)4W12O32 (2 mol%), NaHCO3 (10 mol%) F PhO2S SO2Ph N R R’ h , MeCN F ! R R’ 1.5 equiv. Proposed mechanism 4- [W O ] PhO2S SO2Ph 10 32 N H h!

4- 4- [W10O32] * [HW10O32]

PhO2S SO2Ph N

H F R R’ R R’ R R’

PhO2S SO2Ph N F

synergistic H atom transfer/F atom transfer fluorinates C–H bonds potentially prone to oxidative metabolism

Halperin, S. D., Fan, H., Chang, S., Martin, R. E., Britton, R. Angew. Chem. Int. Ed. 2014, 53, 4690 TBADT-catalyzed fluorination of unactivated C–H bonds

H (TBA)4W12O32 (2 mol%), NaHCO3 (10 mol%) F PhO2S SO2Ph N R R’ h , MeCN F ! R R’ 1.5 equiv.

C–H substrate scope

Me Me Me Me O O F O Me Me F OMe OMe Me F Me Me Me Me Me O Me O 40% 17% (2:1 β:α) 14%

Me F Me Me O O F

H F OAc OAc OAc

79% Me Me Me Me Me Me 13% 15% (2.4:1 β:α) O O O Me Me Me Me O F O Me Me O F O Me OEt Me OEt Me OEt 3 3 Me Me F 58% (4.1:1 β:α) 33% 17%

Halperin, S. D., Fan, H., Chang, S., Martin, R. E., Britton, R. Angew. Chem. Int. Ed. 2014, 53, 4690 TBADT-catalyzed fluorination of leucine on large scale

O O H PhO2S SO2Ph Na4W12O32 (1 mol%) F Me N Me OMe OMe F h!, MeCN:H2O (9:1), 2 h residence time Me NH3HSO4 Me NH3HSO4 1.5 equiv. 90% isolated yield 44.7 g

Me F Me CF3 H N CN N H O

MeO2S

odanacatib potent and selective inhibitor of cathpesin K

large scale for the synthesis of odanacatib (development now discontinued) previously processes required 2-6 steps (F introduced by alkene or epoxide hydrofluorination)

Halperin, S. D., Kwon, D., Holmes, M., Regalado, E. L., Campeau, L.-C., DiRocco, D. A., Britton, R. Org. Lett. 2015, 17, 5200 Outline

Polyoxometalate Fundamentals C–H Oxygenation/Fluorination Reactions

1 1 3 S0 S1 T1 h! ISC H X POM 1(O→M LMCT) 3(O→M LMCT)

C–C Bond-Forming Reactions

H R Early work in TBADT-catalyzed C–C bond-forming reactions

H H

H H Et

3 – 25%

H H

H 4- [W10O32] 18 – 26%

h! O C O H

O 2 – 8% O NC OMe CN

CO2Me 22 °C or 90 °C

low yield & selectivity a b competitive product decomposition 3 – 11% (exclusively b) limited scope 4 – 6% (>13:1 a:b)

Jaynes, B. S., Hill, C. L. J. Am. Chem. Soc., 1993, 115, 12212 Jaynes, B. S., Hill, C. L. J. Am. Chem. Soc., 1995, 117, 4704 Zheng, Z., Hill, C. L. Chem. Commun., 1998, 2467 Hill, C. L. Synlett, 1995, 1995, 127 TBADT-catalyzed acetylation

O Mechanistic evidence H Na4W12O32 Me

h , MeCN H D ! Na4W12O32

h!, 5% D2O 48% yield, 77% selectivity

4- MeCN, 100 HAT [W12O32] * then hydrolysis 50

abundance% / 0 183 184 185 186 187 188 SET m/z before reaction partially reacted 4- 4- [HW12O32] or [H2W12O32]

rare example of a carbanion intermediate in POM photoredox

product deactivated toward further functionalization

Prosser-McCartha, C. M., Hill, C. L. J. Am. Chem. Soc. 1990, 112, 3671 TBADT-catalyzed alkylation of electrophilic alkenes

R H (Bu4N)4(W10O32) (2 mol%) R EWG + EWG R’ h!, MeCN R’ 5 equiv. 1 equiv.

Reaction scope

OH H O O H H H Me Me O

CN 72% 78% 76% 63%

Me CN 50% 75% 50% 65% Me CN

nucleophilic alkyl radicals trapped efficiently by electrophilic alkenes complete conversion " ranges from 0.06–0.58 depending on alkyl radical nucleophilicity

Dondi, D., Fagnoni, M., Molinari, A., Maldotti, A., Albini, A. Chem. Eur. J. 2004, 10, 142 Dondi, D., Fagnoni, M., Albini, A. Chem. Eur. J. 2006, 12, 4153 TBADT-catalyzed alkylation of electrophilic alkenes

R H (Bu4N)4(W10O32) (2 mol%) R EWG + EWG R’ h!, MeCN R’ 5 equiv. 1 equiv.

Proposed mechanism

R EWG R EWG H+ R EWG

R’ R’ R’

4- 4- [W10O32] [HW10O32]

EWG R EWG

R R’ h! R’

[W O ]4-* 10 32 H

R R’

4- electrophilic radical turns over [HW10O32] by SET

Dondi, D., Fagnoni, M., Molinari, A., Maldotti, A., Albini, A. Chem. Eur. J. 2004, 10, 142 Dondi, D., Fagnoni, M., Albini, A. Chem. Eur. J. 2006, 12, 4153 Further studies on TBADT-catalyzed alkylation of electrophilic alkenes

C–H nucleophiles Michael acceptors Me Me H Me CN O H H CO2Et Me Me O

3° C–H bridged bicyclic C–H benzylic C–H SO2Ph

O CN O O H N H R Me CO2Et H2N H H Me O α-amino C–H formamide C–H aldehyde C–H

O H Ph H H Si CO2Me iPrO C N 2 i N CO2 Pr Me Me N CO2Me

β-keto C–H silane Si–H β-pyridyl C–H

Scope has been extended to many classes of C–H nucelophile

Site selectivity is governed by a combination of steric and polar effects

Ravelli, D., Protti, S., Fagnoni, M.. Acc. Chem. Res. 2016, 49, 2232 Ravelli, D., Fagnoni, M., Fukuyama, T., Nishikawa, T., Ryu, I. ACS Catal. 2017, just accepted TBADT-catalyzed cross-dehydrogenative coupling

H (TBA)4W12O32 (4 mol%), K2S2O8 (2 equiv.)

N Me h!, MeCN/DCM 5:1 (0.1 M), 40 °C

20 equiv. N Me

2- + [S2O8] Minisci-type reaction 4- N Me [W10O32] requires 20 equiv. h! C–H nucleophile

[SO ]2- + [SO ]•- + 4 4 N Me 15 examples

H 4- 4- 40-81% yield [W10O32] * [HW10O32]

N Me H [SO ]•- H 4 -H+ N Me N Me H H

Quattrini, M. C., Fujii, S., Yamada, K., Fukuyama, T., Ravelli, D., Fagnoni, M., Ryu, I. Chem. Commun. 2017, 53, 2335 TBADT-catalyzed cross-dehydrogenative coupling

H (TBA)4W12O32 (4 mol%), K2S2O8 (2 equiv.)

N Me h!, MeCN/DCM 5:1 (0.1 M), 40 °C

20 equiv. N Me

C–H nucleophile scope Heteroarene scope Me

N

N 74% 77% 66% 81% 40% O N O O N O N N 53% 73% 69% 60% (24% bis-Cy) 43% (14% bis-Cy) O O O S Me Me N N Me N N H Me N 47% 73% 67% 60% 28% (20% bis-Cy)

Quattrini, M. C., Fujii, S., Yamada, K., Fukuyama, T., Ravelli, D., Fagnoni, M., Ryu, I. Chem. Commun. 2017, 53, 2335 A final comment on visible light-excitable POMs Visible light photocatalysis with polyoxovanadates

+ MeOH H2CO + 2 H h!

UV/vis spectra of [V4] ⇌ [V5]

ΔTa

4- 3- 4- [V4O12] [V5O14] [V10O26]

1 + H2O /2 O2 + 2 H

in situ thermal conversion of {V4} to {V5} allows visible light photoredox catalysis turnover by O2 is quite slow (weeks), but turnover by H2O2 is fast (seconds)

a80 °C Forster, J., Rösner, B., Khusniyarov, M. M., Streb, C. Chem. Commun. 2011, 47, 3114 Visible light photoredox catalysis with heteropolyoxovanadates

Cerium vanadate oxide clusters

2- [(Ce(dmso)3)2V12O33Cl] [(Ce(dmso)4)2V11O30Cl] [(Ce(nmp)4)2V12O32Cl] ( 1 ) ( 2 ) ( 3 )

UV/vis spectra explored for oxidation of pollutants

O H N

N H O indigo (model pollutant)

! ~ 2% for photooxidation of indigo at "ex = 450 nm

Seliverstov, A., Streb, C. Chem. Eur. J. 2014, 20, 9733 POM–photosensitizer co-catalyzed water oxidation

Water oxidation catalyst

2- 2 S2O8

h! >420 nm

2+ 3+ 4 [Ru(bpy)3] 4 [Ru(bpy)3]

Co-POM

10- [Co4(H2O)2(PW9O34)2] + O2 + 4 H 2 H2O key: Co, O, PO4, WO6 Co-POM

POM catalysis can be coupled to external photoredox processes 2+ [Ru(bpy)3] acts as electron shuttle between Co-POM and stoichiometric oxidant

Yin, Q., Hill, C. L., et al. Science 2010, 328, 342 Huang, Z., Hill, C. L., Lian, T., et al. J. Am. Chem. Soc. 2011, 133, 2068