Dichromatic Photocatalytic Substitutions of Aryl Halides with a Small Organic Dye

Article abstract of DOI:10.1002/chem.201705326

Photocatalytic bond activations are generally limited by the photon energy and the efficiency of energy and electron transfer processes. Direct two-photon processes provide sufficient energy but the ultra-short lifetimes of the excited states prohibit chemical reactions. The commercial dye 9,10-dicyanoanthracene enabled photocatalytic aromatic substitutions of non-activated aryl halides. This reaction operates under VIS-irradiation via sequential photonic, electronic, and photonic activation of the simple organic dye. The resultant highly reducing excited photocatalyst anion readily effected C?H, C?C, C?P, C?S, and C?B bond formations. Detailed synthetic, spectroscopic, and theoretical studies support a biphotonic catalytic mechanism.

Full text of DOI:10.1002/chem.201705326

A Journal of
Accepted Article
Title: Dichromatic Photocatalytic Substitutions of Aryl Halides with a
Small Organic Dye
Authors: Axel Jacobi von Wangelin, Michael Neumeier, Raul Perez,
Michal Majek, Diego Sampedro, and Victor de la Pena
O'Shea
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To be cited as: Chem. Eur. J. 10.1002/chem.201705326
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10.1002/chem.201705326
Chemistry - A European Journal
DOI: 10.1002/anie.200((will be filled in by the editorial staff))
Two-Photon Processes
Dichromatic Photocatalytic Substitutions of Aryl Halides with a Small
Organic Dye
Michael Neumeier,[a] Diego Sampedro,[b] Michal Májek,[a] Víctor A. de la Peña O’Shea,[c] Axel
Jacobi von Wangelin[a],[d]* and Raúl Pérez-Ruiz[c]*
Abstract: Photocatalytic bond activations are generally limited by well understood with simple model systems,[8] their applications to
the photon energy and the efficiency of energy and electron transfer more complex organic synthesis settings are scarce. Recent
processes. Direct two-photon processes provide sufficient energy examples of biphotonic activations of aryl halides toward aromatic
but the ultra-short lifetimes of the excited states prohibit chemical substitutions include consecutive photo-induced SET cascades[7a-d]
reactions. The commercial dye 9,10-dicyanoanthracene enabled and triplet-triplet annihilation[7e-f] (Scheme 1, bottom). These
photocatalytic aromatic substitutions of non-activated aryl halides. approaches constitute new modes of reductive bond activation by
This reaction operates under VIS irradiation via sequential photonic, the accumulation of two visible photons which significantly expand
electronic, and photonic activation of the simple organic dye. The the “energy window” of photo-catalytic aromatic substitutions.
resultant highly reducing excited photocatalyst anion readily However, the overall photocatalytic efficiency is still rather low, the
effected C-H, C-C, C-P, C-S, and C-B bond formations. Detailed reaction scope barely explored, the reaction conditions mostly
synthetic, spectroscopic, and theoretical studies support
biphotonic catalytic mechanism.
a
complex, and the mechanistic minutiae of the multicomponent
reactions not fully understood. Therefore, we have initiated a
program that aimed at the extension of the concept of sequential
photonic and electronic activations in order to populate a highly
reducing excited radical anion state of the photocatalyst which
engages in facile reductive bond activation of various aryl-Br/Cl
electrophiles. We believed that a powerful photocatalyst would be a
single small weight organic dye that combines the benefits of
commercial availability, low price, high solubility, high absorbance
of the ground state and the radical anion in the visible region, long
lifetime of the excited states, and facile access to the radical anion.
T
he efficient utilization of visible light for the activation of organic
molecules has been developed to great maturity over the past
decade.[1] However, many of the photocatalytic processes require
activated substrates that facilitate the generation of radical inter-
mediates in the vicinity of heteroatomic functional groups (amines,
carbonyls)[2] or by irreversible reaction steps[3]. Consequently,
photocatalytic activations of unbiased or non-activated substrates
have received very little attention. Generally, the scope of photo-
catalytic bond activations is limited by the energy of the visible
photon (which is sufficient for the cleavage of weak C-I, Csp3-Br and
π-bonds) and the energetic losses during the involved energy and
electron transfers.[4] The reductive cleavage of non-activated aryl
bromides/chlorides by photocatalytic energy transfer or single
electron transfer (SET) is beyond the range of the visible spectrum
which constitutes a severe limitation of arene functionalizations.
Apart from direct UV processes,[5] recent examples of successful
activations of non-activated aryl halides with visible light include
the use of strongly reducing excited iridium photocatalysts (with
transition metal co-catalysts)[6] and indirect two-photon processes
(Scheme 1).[7] The latter approach holds great potential due to its
high modularity by combining different photocatalysts with
photonic activation, energy transfer, and electronic activation steps.
While the physical properties of such biphotonic processes are fairly
E
Scheme 1. Methods of photocatalytic aryl halide activation.
With these framework conditions, we investigated 9,10-dicyano-
anthracene (DCA), a simple molecule that fulfills all afore-
mentioned criteria. The photophysical data of DCA and its radical
anion were reported (Figure 1).[9] While DCA itself is a moderate
photo-oxidant,[10] the oxidation potential (2.5 eV)[11] and lifetime
(~5 ns)[9a] of the excited radical anion DCA●−* are prime qualifica-
tions for its use as a strongly reducing photocatalyst. Applications of
DCA●−* to reductive activations of non-activated aryl halides were
so far not reported. Herein, we demonstrate the competence of DCA
to act as a simple yet powerful photo-reductant in the presence of
low-power visible light. This combination exhibits tangible
advances over the current state of photocatalytic reductive activation
of aryl halides in terms of catalyst and reagents loading, reaction
conditions, and applicability to various aromatic functionalization
reactions. Further, a detailed mechanistic picture of the underlying
photophysical and chemical events was drawn from laser flash
photolysis, steady-state fluorescence, and DFT calculations.
[a] M. Neumeier, M. Majek, Prof. Dr. A. Jacobi von Wangelin
Dept. of Chemistry, University of Regensburg (Germany)
[b] Dr. D. Sampedro
Dept. of Chemistry, CISQ, University of La Rioja (Spain)
[c] Dr. V. A. de la Peña O’Shea and Dr. R. Pérez-Ruiz*
Photoactivated Processes Unit, IMDEA Energy Institute
Ramón de la Sagra 3, 28935, Móstoles (Spain)
[d] Prof. Dr. A. Jacobi von Wangelin*
Dept. of Chemistry, University of Hamburg
Martin Luther King Pl 6, 20146 Hamburg (Germany)
e-mail: axel.jacobi@chemie.uni-hamburg.de
Supporting information for this article is given via a link at
the end of the document.
1
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10.1002/chem.201705326
Chemistry - A European Journal
The optimized conditions (entry 2, Table 1) were applied to various
aryl bromides and chlorides (Scheme 2). Rapid conversions of
challenging electrophiles with an oxidation potential of up to -2.5 V
(vs. SCE in acetonitrile) were observed.[11] Aryl halides bearing
electron-withdrawing substituents showed higher reactivity which is
a direct consequence of the oxidation potentials and the activation
barriers of the SET.[11] The same conditions could be applied to the
alkylation of N-methyl pyrrole.[12]
DCA•¯
DCA
green LED
white LED
blue LED
350
400
450
500
550
600
λ [nm]
Figure 1. Normalized spectra of white, blue, green LED emission (dashed
lines) and DCA (blue line), transient DCA●− absorption (green line).
The small organic dye DCA has three distinct absorption bands in
the visible near-UV-to-blue region while the radical anion DCA●−
absorbs green light.[9] The need of simultaneous irradiation with
green and blue light was circumvented by an operationally simpler
setup with a single cold-white LED that exhibits very similar
emission and no tailing into the UV (Figure 1). We studied the
reaction of 4-bromobenzonitrile (1) and the electron-rich N-methyl
pyrrole (Table 1).[11] Initially, we adopted literature conditions[7a] in
the presence of a high excess of N-methyl pyrrole and diisopropyl-
ethylamine (DIPEA) which afforded with 10 mol% photocatalyst
very good yields of 2a (entry 1). The high catalytic efficiency of
DCA even allowed a significant optimization of the reaction
conditions under irradiation with a single cold-white LED for 5 h at
20 °C (higher substrate concentration, lower excess of N-methyl
pyrrole, no excess of amine, entry 2). In the absence of either
component (catalyst, pyrrole, base, light), no cross-coupling was
observed (entries 3-5). The poor reactivity with either blue (455 nm)
or green light (525 nm) irradiation supports the notion of a dual
photo-activation by excitation of DCA and its radical anion (entry
6). It is important to note that the photocatalyst exhibited good
solubility in acetonitrile and good stability toward bleaching and
Scheme 2. Substrate scope of the 2-aryl pyrrole synthesis. Conversions in
parentheses if not >90%. [a] 40 equiv. N-methyl pyrrole.
We postulate a reaction mechanism that commences with the
selective excitation of DCA with blue light to the excited singlet
1
state DCA* (Scheme 3). From fluorescence quenching studies in
the presence of DIPEA (Figure 2, top), a quenching rate constant of
kq(S1) = 2.3·1010M -1s-1 was calculated[11] which indicates that the
radical ion pair formation (DIPEA●+ DCA●−) in the first catalytic
turnover occurs at diffusion rates. Fluorescence studies documented
that the quenching with DIPEA is the major deactivation pathway of
1DCA* (99%) which proves the high efficiency of catalytic reaction
initiation.[11] Excitation of DCA●− with green light results in the
formation of DCA●−*. This highly reducing species effects
mesolysis of aryl bromides and chlorides to give Ar● which was
confirmed by TEMPO trapping.[11] Reaction of Ar● with N-methyl
pyrrole gives a cyclic vinylogous amino radical which undergoes
thermodynamically favoured oxidation by DCA* (G = -2.7 eV).
Experimental support for this process rather than the SET from
DIPEA comes from the high synthetic efficiency of reactions in the
presence of only 1.1 equiv. DIPEA despite the consumption of
1 equiv. base in the terminal acid-base reaction with HBr (entry 2,
Table 1 and Scheme 2). SET between the cyclic -enamine radical
intermediate with ground state DCA is 4.55 kcal mol-1 (0.2 eV)
uphill. The quasi co-catalytic role of amine for the initiation of
photocatalysis is also evident from the fact that little to no hydro-
dehalogenation was observed under standard conditions as, unlike
literature protocols,[7a] no excess of DIPEA was employed and the
majority of amine resides as HBr salt. Reaction of 1a in d3-
acetonitrile gave no deutero-benzonitrile.
decomposition. Quantitative analysis of
a standard reaction
documented a loss of less than ¼ of the catalyst concentration at
total conversion of 1.[11]
Table 1. Optimization of reaction conditions.[a]
Entry Deviations from conditions above
2 [%] [b]
0.04 M 1, 10 mol% DCA, 2 equiv. DIPEA, 40
equiv. N-methyl pyrrole, 2 h
1
87 [c]
2
3
4
5
no
85
as entry 1, w/out N-methyl pyrrole
as entry 1, w/out photocatalyst or w/out base
as entry 1, in the dark
0 (64) [d]
0 (0)
0 (0)
6
as entry 1, blue (455 nm) or green LED (525 nm) <4 (<10)
[a]
1 (0.2 M), DCA (5 mol%), DIPEA (1.2 equiv.), N-methyl pyrrole (20
equiv.) in MeCN (1 mL); irradiation (cold-white LED, >410 nm), 20 °C,
[b]
[c]
5 h. GC yields of 2; conversion in parentheses if not >95%. 82%
isolated yield. [d] 45% benzonitrile as single product.
2
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10.1002/chem.201705326
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Laser flash photolysis
and kinetic analysis was derived from DFT calculations (CAM-
B3LYP/6-31++G**).[11] The 1e-reductions of 1a and the other
reactive electrophiles by DCA●−* are thermodynamically feasible
(ΔG2 0). The kinetic barriers toward the radical anion ArX●− are
generally small (ΔG2 = 0-0.3 eV). The trend of substrate reactivity
is very accurately mirrored by the thermodynamic and kinetic data
which predict unfavourable Gibbs energies and higher activation
barriers only for the reactions of electron-rich aryl halides.[11]
However, low reactivity can be a direct consequence of reversibility
of the electron transfer and subsequent mesolysis. The insufficient
reducing power of ground-state-DCA●− (-0.6 to -0.89 V vs. SCE) for
the reductive activation of aryl bromides (DFT: ΔG1 >0) was
demonstrated by laser flash photolysis experiments which showed
identical decay traces of DCA●− in the absence and in the presence
of 1a, respectively (at 520 nm, see Figure 2, bottom). This
observation is in full agreement with the thermodynamics of this
hypothetical SET event.[11]
DFT: G1 >0
Eox  2.5 eV vs. SCE
Fluorescence quenching
dichromatic
photocatalysis
DFT: G2<0
G2 <0.3 eV
DFT:
G =
2.7 eV
No radical
chain mechanism
Scheme 3. Key experimental and theoretical data in support of a reaction
mechanism that involves sequential photonic, electronic, and photonic
activation of DCA.
The scope of dichromatic photocatalytic aromatic substitutions
could also be extended to other C-heteroatom functionalizations
(Scheme 4). The DCA-catalyzed reaction enabled phosphorylation
at low catalyst loading and catalytic (10 mol%!) amine
concentration,[13] sulfide formation from disulfide,[14] and the metal-
200
150
free borylation from diborane[15]
.
Emission
[a.u.]
100
50
0
400
450
500
550
600
λ [nm]
0.01
Scheme 4. Method extensions to C-Het couplings. [a] 10 mol% DIPEA.
In conclusion, we have developed an operationally simple photo-
catalytic reductive activation of aryl halides under mild conditions.
Synthetic, spectroscopic, and theoretical studies support the notion
of a dichromatic photocatalysis mechanism which does not require a
sacrificial reductant. Sequential photonic, electronic, and photonic
activation of 9,10-dicyanoanthracene, a simple, low-molecular
weight, soluble, and photostable organic dye, resulted in the
formation of the strongly reducing excited radical anion DCA●−*
that is capable of cleaving unactivated C-halide bonds. Photo-
catalytic applications to aromatic C-H, C-C, C-S, C-P, and C-B
bond formations were demonstrated. Further endeavours toward the
development of effective biphotonic activations with simple organic
dyes are currently being investigated.
A
[a.u.]
0.00
0
25
75
100
150
50
125
t [ms]
Figure 2. Top: Fluorescence quenching of DCA (0.01 mM) with DIPEA (0,
4, 8, 11, 15, 19, 28, 39 mM) in MeCN/air. DCA absorption: 0.5 (λexc 400 nm).
Inset: Stern-Volmer plot for kq(S1). Bottom: DCA decay monitored at
520 nm after laser flash photolysis (355 nm; 10 mJ/pulse): DCA (10-4 M),
Et3N (6·10-2 M), MeCN, Ar: without 1 (black), with 10-3 M 1 (red).[11]
−
●
Acknowledgement
We thank the Marie Curie program of the European Union (PIEF-GA-
2013-625064, R.P.R.), the Comunidad de Madrid (2016-T1/AMB-
1275), the Fonds der Chemischen Industrie (fellowship, M.N.) and
MINECO/FEDER (CTQ2014-59650-P). We acknowledge the
Supercomputing Centre of Galicia (CESGA) for CPU time and the
DFG Graduate School “Photocatalysis”.
An alternative radical chain mechanism via SET from the 2-aryl-
2H-pyrrol-3-yl radical to ArX is thermodynamically prohibited
(G >30 kcal mol-1).[11] Likewise, the halogen atom transfer from
ArHal to the same intermediate is an uphill process. We believed
that the SET from the excited radical anion DCA●−* (-2.5 eV vs.
SCE) to the aryl halide would constitute the rate-limiting step in
reactions with deactivated electrophiles. A detailed thermodynamic
Conflict of interest
3
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10.1002/chem.201705326
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Keywords: photocatalysis · two-photon processes · aryl halides ·
cross-coupling · organic dyes
The authors declare no conflict of interest.
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Published online on ((will be filled in by the editorial staff))
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4
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Chemistry - A European Journal
Entry for the Table of Contents
Two-photon processes
Michael Neumeier, Michal Majek, Diego
Sampedro, Víctor A. de la Peña O’Shea,
Axel Jacobi von Wangelin,* and Raúl
Pérez-Ruiz* __________ Page – Page
Dichromatic Photocatalytic
Substitutions of Aryl Halides with a
Small Organic Dye
Two photons to tango: A highly reducing photocatalytic system was
developed that involves the sequential combination of photonic, electronic, and
photonic activation of 9,10-dicyanoanthracene, a simple commercial and
soluble organic dye. The ultimately formed excited radical anion DCA•−*
enables the reductive activation of various aryl bromides and chlorides under
mild conditions and the application to hetero-biaryl cross-coupling and
heteroatom functionalizations. Detailed spectroscopic and theoretical studies
support the postulated dichromatic photocatalytic mechanism.
5
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10.1002/chem.201705326
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6
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