Hybridization of Nickel Catalysis
and Photoredox Catalysis

Literature seminar#1
B4 Hiromu Fuse
2017/02/04(Sat)Introduction

MacMillan, D. W. C. et al. Science 2016, 352, 1304.

• Novel cross coupling was reported!
• Highly selective sp3 C-H functionalization!
• New possibility of Photoredox Catalysis!

What lies behind this discovery?

2

Introduction

The pioneer of Photoredox Catalysis!

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Today’s Content

1. Nickel-catalyzed cross-coupling via
radical pathway
2. Hybrid catalysis of photoredox
catalysis and nickel catalysis
3. Hybrid catalysis of photoredox
catalysis, nickel catalysis and HAT
catalysis4Today’s Content

1. Nickel-catalyzed cross-coupling via
radical pathway
2. Hybrid catalysis of photoredox
catalysis and nickel catalysis
3. Hybrid catalysis of photoredox
catalysis, nickel catalysis and HAT
catalysis5Comparing Cross-Couplings• Traditional cross-coupling• Mainly for sp2-sp2 bond formation
because of slow oxidative addition into alkyl halide and β-hydride elimination asside reaction

Ni catalyst has other possibility.

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Nickel Catalysis

Jamison, T. F. et al. Nature 2014, 509, 299.
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Nickel-Catalyzed Cross-CouplingFu, G. C. et al. J. Am. Chem. Soc. 2008, 130, 12645.

• sp3 electrophile can be used!
• enantioselective cross-coupling from a racemic compound.

How does this reaction proceed?
8Firstly Proposed Cycle• Transmetalation before oxidative addition?
9Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Synthesis of Nickel Complex(BArF4 = tetrakis(3,5-bis(triﬂuoromethyl)phenyl)borate)• Nickel(I)complex (2) wasconfirmed byboth ESI-MS andEPR spectrum
10Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Stoichiometric Reaction• Although in both cases reactions occurred, the reaction ofphenylnickel(II) was more consistent with the normal reaction.
11Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Oxidative Addition via Radical Pathway• TEMPO traps propargylic radical. It is confirmed by ESI-MS.
(calculated for C19H37NOSi+H+: 324.2717, observed: 324.2724)
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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Radical Propagation• Is Ni(I) complex (3) serves aninitiator for carbon-carbon bondformation through radical chainprocess?
• Is enantioselectivity determined byNi(II) complex (1)?

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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Radical Propagation• ((iPrPybox)Ni(I)Br) initiates radical process.
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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Radical Chain Mechanism• Oxidative addition through bimetallic mechanism
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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Stoichiometric Reaction• When the reaction ismonitored by EPRspectroscopy, no signal isobserved. So, nickel(I) andnickel (III) complexes are notpresent in significant
quantities.

Analyzed by 19F-NMR• The consumption ofnickel(II) complex (4)directly correlates theformation of couplingproduct.

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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Newly Proposed Cycle

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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Confirmation of Transmetalation Step

UV-vis spectroscopy• The result suggests that transmetalation step is rational.
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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Confirmation of Transmetalation StepESI-MS• ESI-MS also suggests that transmetalation step is rational.
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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Catalytic Reaction

UV-vis spectroscopy• The result confirms rapid formation of ((iPrPybox)Ni(II)Ph)+.
• When the catalytic process is analyzed by EPR spectroscopy, it isfound to be EPR silent. It suggests that most of nickel complex
exist as ((iPrPybox)Ni(II)Ph)+.
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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Catalytic Reaction• (iPr-pybox)Ni(II)Ar was generated more than propargylic radical,
otherwise homocoupling of propargylic radical would occur.
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Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Catalytic Reaction• In the presence of TEMPO, (iPr-pybox)Ni(II)Ar was consumed, andcross-coupling product was not observed.
22

Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Nickel-Catalyzed Cross-Coupling• sp3-sp2 cross-coupling!
• Nickel(II) can intercept
radical species!
• However, nucleophile islimited, and it sometimes
diminishes functional grouptolerance.

23

Fu, G. C. et al. J. Am. Chem. Soc. 2014, 136, 16588.

Today’s Content

1. Nickel-catalyzed cross-coupling via
radical pathway
2. Hybrid catalysis of photoredox
catalysis and nickel catalysis
3. Hybrid catalysis of photoredox
catalysis, nickel catalysis and HAT
catalysis24Hybrid Catalysis of Photoredox Catalysis andNickel Catalysis

25

Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

Photoredox Catalysis• MLCT and ISC give longlived triplet photoexcitedstate.
• Photoredox catalyst canwork as both strong oxidant
and strong reductant.

MLCT: metal to ligand charge transfer
ISC: intersystem crossing
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MacMillan, D. W. C. et al. Chem. Rev. 2013, 113, 5322.

Photoredox-Catalyzed Reaction

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MacMillan, D. W. C. et al. J. Am. Chem. Soc. 2014, 136, 11602.

Photoredox-Catalyzed Reaction
Ex.

• Photoredox catalysis can generate carbon-centered radical.
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MacMillan, D. W. C. et al. J. Am. Chem. Soc. 2014, 136, 11602.

Working Hypothesis•• Generate carbon-centeredradical•• However, electrophile islimited such as vinyl sulfone,or cyanoarene.

C-C bond formation via
radical pathway
However, nucleophile islimited such as organoboron, organo-zinc, organostannanes, or Grignard
reagents.

Ni catalyst can intercept radical species
generated by photoredox catalyst and catalyze
cross-coupling?

29Hybrid Catalysis of Photoredox Catalysis
and Nickel Catalysis

30

Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

Proposed Catalytic Cycle

31

Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

E1/2 (Half-Wave Potential)• E1/2…The tool for discussion about whether single electron transfer
proceeds or notred→ red⁺ + e⁻ …largely negative E1/2 = strong reductant
ex. Cp2Co (E1/2= -1.16 V)
ox + e⁻ → ox⁻…largely positive E1/2 = strong oxidant
ex. TCNQ-F4 (E1/2= +0.61 V)• E1/2 (oxidant) - E1/2 (reductant)>0…reaction proceeds (single electron transfer can proceed)
32<0…reaction does not proceed (single electron transfer cannot)

How to determine E1/2? -Cyclic Voltammetry-

http://www.tek.com/blog/performingcyclic-voltammetry

金属錯体の電子移動と電気化学（錯体化学選書）• The experiment to measure E1/2
• In this experiment, voltage is changed in certain rate in solvent
which contains electrolyte.
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How to determine E1/2? -Cyclic VoltammetryElectric Current

Mainly exist as A↔

Mainly exist as A+Voltage• Cyclic Voltammetry reveals E1/2
• E1/2 = (Epc+Epa)/2金属錯体の電子移動と電気化学 （錯体化学選書）
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Reaction proceeds or not?

35Other Possibility

Ni(0) undergo oxidativeaddition more readily
than Ni(I).
Amatore, C. Organometallics, 1988, 7, 2203

So proposed as previous slide
36
Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

Substrate Scope• N-Heterocycles also work as electrophile.
37

Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

Substrate Scope• Thioether can tolerate reaction conditions.
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Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

Substrate Scope

KOH is used as base.

• Direct C-H functionalization was also achieved in case of anilinederivatives.

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Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

Hybrid Catalysis of Photoredox catalysis andNickel Catalysis• sp3-sp2 bond formation via feedstock chemicals!
• However, nucleophile was limited. (only easy to abstract one
electron (ex. sp3 C-COOH))
40

Doyle, A. G.; MacMillan, D. W. C. et al. Science 2014, 345, 437.

Today’s Content

1. Nickel-catalyzed cross-coupling via
radical pathway
2. Hybrid catalysis of photoredox
catalysis and nickel catalysis
3. Hybrid catalysis of photoredox
catalysis, nickel catalysis and HATcatalysis

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Ternary Catalysis

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MacMillan, D. W. C. et al. Science 2016, 352, 1304.

HAT Process• HAT (Hydrogen Atom Transfer) process iseffective way to access radical intermediates.
ex.

Ishii, Y. et al. J. Org. Chem. 1995, 60, 3934.

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Polar Effect of HAT Process• Although BDE is important, polar effect isalso important.
El·+ H–Nuc → El–H+Nuc·｝favored
Nuc· + H–El→ Nuc–H +El·
El1· + H–El2 → El1–H +El2·｝disfavored
Nuc1· + H–Nuc2 → Nuc1–H +Nuc2·
El·: elecrophilic radicalNuc·: nucleophilic radicalRoberts, B. P. Chem. Soc. Rev. 1999, 28, 25.
44Quinuclidine as HAT Catalyst• Strong BDE (H-N+ BDE= 100 kcal/mol vs S-H BDE= 87 kcal/mol)• Amine radical cation could abstract hydridic C-H bond
• Rigid bicyclic structure prevents α-deprotonation
MacMillan, D. W. C. et al. Science 2015, 349, 1532.
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Working Hypothesis

Nickel catalyst mightintercept radicalspecies like this?
MacMillan, D. W. C. et al. Science 2015, 349, 1532.
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Ternary Catalysis

Nickel catalyst

Photoredox catalyst

HAT catalyst47

MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Proposed Catalytic Cycle

48

MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Cyclic Voltammetry

Epc could not beconfirmed maybe
because ofdecomposition orside reaction.
Irreversible oxidation event at +1.22 V vs SCE in MeCN
So, Epa= +1.22 V

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MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Reaction proceeds or not?

50

MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Substrate Scope• N-Heterocycles also can tolerate reaction conditions.
51

MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Substrate Scope• Fluorine and hydroxyl group could tolerate reaction condition.
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MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Substrate Scope• Regioselectivity is unique about unsymmetrical amine. Maybe, it ishighly influenced by kinetics.
• α-Oxy sp3 C-H bond and benzylic C-H bond are also functionalized.
53

MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Other Possibility• There is possibility of nickeluncatalyzed cycle like this54

MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Control ExperimentControl experiment for N-Heterocycles as electrophiles was performed
Deny nickel-uncatalyzed cycle
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MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Ternary Catalysis• Selective functionalization of sp3 C-H bond which is mostabundant structure on the organic compounds.

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MacMillan, D. W. C. et al. Science 2016, 352, 1304.

Conclusion

1. Nickel-catalyzed cross-coupling via
radical pathway– sp3-sp2 bond formation via radical pathway

2. Hybrid catalysis of photoredox
catalysis and nickel catalysis– sp3-sp2 bond formation with simple and readily available
organic molecules as nucleophile

3. Hybrid catalysis of photoredox
catalysis, nickel catalysis and HAT
catalysis– sp3-sp2 bond formation with sp3 C-H bond as nucleophile57