Photoredox Organocatalysis

Literature seminar#2
M1 Hiromu Fuse
2017/07/15(Sat)Introduction

Nicewicz, D. A. et al. Science 2015, 349, 1326.

• Organic photoredox catalyzed reaction!
• Direct C-H amination!
• Access to simple aniline derivatives from ammonium

What stage did
the photoredox achieve?

2Introduction
Dave was born and raised in central New Jersey. He
completed his B.S. (2000) and M.S. (2001) in Chemistry at
the University of North Carolina at Charlotte under thedirection of Craig Ogle. Dave then went on to the Universityof North Carolina at Chapel Hill, where he did his Ph.D.
studies under the tutelage of Jeffrey Johnson. Under Jeff’sdirection, Dave investigated the use of the Brook
rearrangement in synthetic methodology and its application
to the total synthesis of zaragozic acid C. Upon completionof his Ph.D. studies in 2006, Dave returned to his native
New Jersey where he was a Ruth L. Kirschstein National
Institutes of Health Postdoctoral Researcher in thelaboratories of Professor David MacMillan at Princeton
University. While in MacMillan’s lab, Dave helped develop
the budding area of photoredox organocatalysis. In July of2009, Dave returned to UNC as an Assistant Professor ofChemistry.
http://www.chem.unc.edu/people/faculty/nicewicz/group/biography.html

The pioneer of Photoredox Catalysis!

3Introduction

Nicewicz, D. A.; MacMillan, D. W. C. Science. 2008, 322, 77.

The pioneer of Photoredox Catalysis!

4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
5MacMillan, D. W. C. et al. Chem. Rev. 2013, 113, 5322.

High potential of Mes-Acr+Ir(dFCF3ppy)2(dtbpy)+

Ir(III)*/Ir(II)= 1.21 V
Ir(IV)/Ir(III)= 1.69 V
ex. S2O82- = 1.85 V
HOCl = 1.39 V

Ru(bpy)32+
Ru(II)*/Ru(I)= 0.77 V
Ru(III)/Ru(II)= 1.29 V

Mes-Acr+Et (S*/S )= 2.06 V

http://chemlabs.princeton.edu/macmillan/photoredox/
6Today’s Content

1. Mechanistic study of Mes-Acr+ catalyzed
anti-Markovnikov hydro-functionalization
2. Direct C-H amination

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Today’s Content

1. Mechanistic study of Mes-Acr+ catalyzed
anti-Markovnikov hydro-functionalization
2. Direct C-H amination

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Anti-Makovnikov hydro-functionalization• Although anti-Markonikov hydro-functionalization was developed, there
is no general way.
• In many cases, substrates are limited such as vinylarenes orprefunctionalized heteroatom reagents.

Studer, A. et al. J. Am. Chem. Soc. 2007, 129 , 4498.

Buchwald, S. L. et al. J. Am. Chem. Soc. 2013, 135, 15746.
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Photoredox-catalyzed anti-Makovnikov
hydro-functionalization

Nicewicz, D. A. et al. J. Am. Chem. Soc. 2012, 134, 18577.
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2013, 135, 10334.
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2013, 135, 9588.
Nicewicz, D. A. et al. Angew., Chem. Int. Ed. 2014, 53, 6198.
Nicewicz, D. A. et al. Nat. Chem. 2014, 6, 720.
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Nicewicz, D. A. et al. Chem. Sci. 2013, 4, 3160.

Proposed mechanism

How does this reaction proceed?
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Difficulty of mechanistic study

1. Multicomponent catalytic systems

2. Short-lived intermediate
3. SET (Single Electron Transfer)

Spectroscopic study was employed.
12Proposed mechanism• SET between alkene
and Mes-Acr+• State of Mes-Acr+

How does this reaction proceed?
13
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

The state of Mes-Acr+• Which state was involved?

Confirm potentialof Mes-Acr+

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Fate of excited state

In today’s case,
M: Mes-Acr+
Q: alkenes
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photochemistry.wordpress.com

Stern-Volmer PlotKSV= kq τ0(KSV: Stern-Volmerconstant)grow linearly with [Q]16Stern-Volmer Plotkq (rate of deactivation by quencher)
τ: lifetime of M* (excited state of M)
KSV: Stern-Volmer constantτ0/τ= 1+kq[Q]τ0= 1+KSV[Q]kq = KSV / τ0possible17
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Rate of quenchingk1 = kq (rate of deactivation byquencher)
KSV: Stern-Volmer constant
k1 = kq= KSV / τ0

SET is possible.

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

How to confirm potential of excited state?
• Rehm-Weller plot
– Experimental techniques• E*red = E0,0 + Ered
– Calculation approach

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Rehm-Weller plot(＋)

E (消光剤の電位)(－)

金属錯体の電子移動と電気化学 （錯体化学選書）• Potential could be revealed by Rehm-Weller plot.

20Rehm-Weller plot

• Potential of Singlet State was needed.

Which is the dominant state, LES or CTS?
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

What is the motivation?

CTS• mesityl radicalcation islimited toredox
potential.

LES• Suppressing
intramolecularchargetransfer could
lead moreoxidizing
acridinium
catalyst.

22
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

How to confirm?

compare the spectrums of these two species

23Comparing spectrum

LE• There waspossibility that CT
was not
necessary?

CTdominant species?
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Proposed mechanism• Cation radical intermediate• k2(rate of cyclization)

How does this reaction proceed?
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Transient absorption spectroscopy• It can detect the chemicals which have short life.
金属錯体の電子移動と電気化学 （錯体化学選書）

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Transient absorption spectroscopy• It can detect the chemicals which have short life.
金属錯体の電子移動と電気化学 （錯体化学選書）

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Detection of cation radical intermediate(OD= absorbance)• The spectrum of cation radical is obtained by subtraction of Mes-Acr ·from the transient absorption spectrum at 500 ns.

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Detection of cation radical intermediate• Each cation radical could be observed.

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Detection of cation radical intermediate• Transient absorption spectroscopy at 40 ns

T: triplet state of Mes-Acr+
CR: cation radical• In 40 ns, cyclization was finished. ➡ k2> 2.5× 107 s-1

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Proposed mechanism

When PhSH is used as
HAT catalyst, (PhS)2 isobserved as byproduct.

How does this reaction proceed?
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Disulfide crossover experiment• Disulfides were competent HAT catalysts .
• Disulfide bond was cleaved by visible light irradiation.
32
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Proposed mechanism

SET between MesAcr・and radicalspecies

How does this reaction proceed?
33
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

How to confirm?

observed at 520 nm
observed at 445 nm• Reduction by CoCp2 produces Mes-Acr・.
• λex= 410 nm, where Mes-Acr· absorption is at a minimum.

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Transient absorption spectroscopy• 520 nm indicates Mes-Acr・.
• 445 nm indicates a combination of Mes-Acr+ growth and PhS·decay.
• kobs confirms that MesAcr+ grows in at the same rate that MesAcr· disappears.
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Control experiment• In the absence of (PhS)2, no change was confirmed.

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Proposed mechanism

Computational study
Why PhSH or (PhS)2
is superior to PMN?

How does this reaction proceed?
37
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

HAT process
lowest energy
configuration

PhSH

PMN

transition state• The calculated activation
free energy barrier for
HAT is 9.5 kcal mol-1 for
PhSH, as compared with
15.1 kcal mol-1 for PMN.

• Owing to structure
reorganization, HAT
process is less costly forPhSH.
• k4 for PhSH is 6.2×105 M-1
s-1(for PMN is 5.0×101 M-1s-1)
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Preparative scale reaction kinetics• In condition D, reaction proceeded faster.
• In both conditions, PhSH is dominant species.
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Preparative scale reaction kinetics

UV-vis spectroscopy

Red= 0 min, Orange= 1 min, Yellow= 2 min, Cyan= 3 min
Time traces of absorbance at 450 nm (Mes-Acr+) and 520 nm (Mes-Acr・)are highlighted in blue.

• In both cases, Mes-Acr+ and Mes-Acr・were not detectable in earlystages.

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Resting state of Mes-Acr+• Reversible adduct can explain that absorption for both Mes-Acr+and Mes-Acr・ was not detectable, but Mes-Acr+ could be isolated
after reaction was completed.

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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Recovery of Mes-Acr+• Recovery of Mes-Acr+ was observed.
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Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Rate-limiting factors

1. Deprotonation step has rate-limitingeffect?
– (PhS)2 does not depend on HAT for generation of thiyl
radical.
– PhSH is required to encounter radical 4 (benzyl radical).

2. Off-cycle intermediate

43
Nicewicz, D. A. et al. J. Am. Chem. Soc. 2014, 136, 17024.

Today’s Content

1. Mechanistic study of Mes-Acr+ catalyzed
anti-Markovnikov hydro-functionalization
2. Direct C-H amination

44

Direct C-H amination

Nicewicz, D. A. et al. Science 2015, 349, 1326.
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Outline of arene C-H amination

Nicewicz, D. A. et al. Science 2015, 349, 1326.
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Photoredox-Catalyzed Reaction• Improve yield• Diminish byproductNicewicz, D. A. et al. Science 2015, 349, 1326.
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Optimization of Mes-Acr+

In initial study, cat A or cat B could not be
observed in crude NMR.

Nicewicz, D. A. et al. Science 2015, 349, 1326. 48

Plausible catalytic cycle

Nicewicz, D. A. et al. Science 2015, 349, 1326. 49

Substrate scope for arenes

For 16 and 17, reactions run with 2.0 equivalents of arene, 1.0 equivalent ofamine, and 1.0 equivalent of TEMPO under an N2 atmosphere for 44 hours.
Nicewicz, D. A. et al. Science 2015, 349, 1326.
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Substrate scope for amines
For 38, a reaction run under N2
with 1.0 equivalent of TEMPO.

Nicewicz, D. A. et al. Science 2015, 349, 1326.
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Application for late-stage functionalization

Nicewicz, D. A. et al. Science 2015, 349, 1326.
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Synthesis of aniline from ammonia

Hartwig, J. F. et al. J. Am. Chem. Soc. 2009, 131,11049.

• Ammonia is one of the most abundant N1 sources.
• However, metal-catalyzed amination using ammonia is very rare.

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Synthesis of aniline• Benchtop-stable solid salt which is less costly on a molar basis thanliquid ammonia could be used as N1 source.

Nicewicz, D. A. et al. Science 2015, 349, 1326.
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Substrate scope for aniline

Nicewicz, D. A. et al. Science 2015, 349, 1326.
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Direct C-H amination

Nicewicz, D. A. et al. Science 2015, 349, 1326.
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The photoredox organocatalyst

1. High potential in catalytic amount– Access to unstable intermediate

2. Easily tunable system– Changing stability and redox potential based on organicstructure57