Novel Oxidative Ugi Reaction for the Synthesis of Highly Active, Visible-Light, Imide-Acridinium Organophotocatalysts

Article abstract of DOI:10.1002/chem.201802830

A newly designed class of acridinium-based organophotocatalysts bearing an imide group at the C9-position is presented. To achieve these unprecedented structures, a synthetic strategy based on a novel straightforward oxidative Ugi-type reaction at the benzylic position of C9-unsubstituted acridanes was developed. The introduction of the imide-unit affords a notable photocatalytic activity enhancement, allowing efficient transformations in different oxidative and reductive visible-light catalytic reactions.

Full text of DOI:10.1002/chem.201802830

A Journal of
Accepted Article
Title: Novel Oxidative Ugi-Reaction for the Synthesis of Highly Active
Visible Light Imide-Acridinium OrganoPhotocatalysts
Authors: Andrea Gini, Mustafa Uygur, Thomas Rigotti, Jose Aleman,
and Olga García Mancheño
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To be cited as: Chem. Eur. J. 10.1002/chem.201802830
Link to VoR: http://dx.doi.org/10.1002/chem.201802830
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COMMUNICATION
Novel Oxidative Ugi-Reaction for the Synthesis of Highly Active
†
Visible Light Imide-Acridinium OrganoPhotocatalysts
Andrea Gini, Mustafa Uygur, Thomas Rigotti, José Alemán* and Olga García Mancheño*
Abstract:
A
newly designed class of acridinium-based
negative impact of this substitution in the kinetics of
photocatalytic reactions can be attributed to the steric hindrance
imposed by the mesityl group. Although there are several
publications related to the use of acridinium salts as
photocatalysts, only compounds that present alkyl and aryl
organophotocatalysts bearing an imide group at the C9-position
is presented. To achieve these unprecedented structures, a
synthetic strategy based on a novel straightforward oxidative
Ugi-type reaction at the benzylic position of C9-unsubstituted
acridanes was developed. The introduction of the imide-unit
affords a notable photocatalytic activity enhancement, allowing
efficient transformations in different oxidative and reductive
visible light catalytic reactions.
[
9,10]
substituents at the C9-position have been reported.
Therefore, in order to achieve a higher performance and
broaden synthetic applicability, new acridinium-type catalysts
bearing different functional groups are needed.
Visible light photoredox catalysis has been established as a
powerful tool for the synthesis of molecules by selective
activation of bonds under mild conditions. Therefore, access to
unique reactivities are possible, including those thermally
[
1]
forbidden or difficult to carry out by other methodologies. The
catalysts involved in most of the photocatalytic processes are
[
2]
based on Ru(II) and Ir(III) complexes. More recently, the
possibility of using organic photoredox catalysts for synthetic
Figure 1. Previous acridinium-photocatalysts and reactivity at the C9-position.
[
3]
transformations has been extensively investigated. This type of
photocatalysts are suitable for industrial applications because of
their remarkable photophysics and electrochemical properties
Based on our extended experienced on oxidative C-H
[
11]
functionalization
for the synthesis of biological and important
[
3]
[12]
(
e.g. as powerful oxidant). In addition, the low price and low
pharmaceutical compounds, we decided to introduce a polar
group at C9 by exploiting the direct C-H bond functionalization
technology on acridane scaffolds, followed by an oxidative
aromatization to the corresponding acridinium salts (Scheme
toxicity of these photoredox active organic dyes compared to the
commonly used transition metal-based photocatalysts make
them very attractive.
[
12a]
Among well-established organophotocatalysts, acridinium
derivatives represent a specific family that contains extended
conjugated π-systems and absorb light in the visible region
1).
For this purpose, we focused on the Ugi multicomponent
reaction (Ugi-MCR), as one of the most potent and convenient
methodology for the synthesis of a large variety of bisamides
[
4]
[13]
(
Figure 1, left). In the excited state, acridinium ions are usually
and imides. The Ugi reaction implies a cascade of elementary
powerful oxidants, whereas they are weak reductants. In
addition, they show good quantum yields in some reactions and
chemical transformations between amines, aldehydes (or
ketones), isocyanides and carboxylic acids to assemble, via the
formation of a key iminium intermediate, a single amide-type
product. Despite the outstanding applications developed in the
past decades, all the reported few examples on oxidative Ugi
multicomponent reactions (Ox-Ugi-MRC), which proceed by a
[
4d,5]
extremely long lifetime of fluorescence.
However, the first
generation of this group of photocatalysts, unsubstituted or C9-
aryl substituted N-methyl acridinium ions (type I), has only found
limited use due to its susceptibility to the nucleophile addition at
the 9-position in the ground state, or by the addition of radical
species to its corresponding acridinyl radical (Figure 1, I and II,
3
(sp )C-H bond oxidation at the substrate, relay on the formation
[
14]
of a key iminium salt.
Moreover, as far as we know, the
[
6,7]
respectively).
In order to avoid this drawback, in 2004
mesityl group at the C9-position.
synthesis of acridinium imide derivatives has not been reported
to date. In addition, the synthesis of these acridinium derivatives
(top, Scheme 1) required the use of Grignard or organolithium
Fukuzumi introduced
a
Therefore, the stability of the photocatalyst under the reaction
conditions was increased by blocking the access of the
nucleophiles and radical species to the photocatalyst (Figure 1,
[
15]
derivatives, high temperatures or strong acids,
making
essentially these methodologies functional group non-tolerant.
Concern by the lack of precedents, and in order to achieve our
targeted imide-photocatalyst, we envisioned the development on
a novel Ugi-multicomponent reaction based on an in situ
generated key carbocation electrophilic intermediate (or
arylogous iminium ion), which will allow to easily tune the
substitution on the final structure (Scheme 1, bottom).
8
III). Although the stability of the Fukuzumi´s catalyst III was
substantially enhanced to respect to the first generation, the
kinetic of the reactions was significantly diminished. The
[a]
Prof. O. García Mancheño, M. Uygur,
Organic ChemistryInstitute, University of Münster, 48149 Münster.
E-mail: olga.garcia@uni-muenster.de
Herein, the straightforward synthesis of a novel family of
imide-acridinium photocatalysts based on the first modular, mild
oxidative Ugi-type reaction on dibenzylic substrates is
presented. Furthermore, their photochemical properties,
applications as highly potent organophotocatalyst, and their
distinct reactivity respect to a commercially available and well-
established acridinium salt, are discussed.
[
b]
c]
Prof. O. García-Mancheño, Dr. A. Gini, Institute for Organic
Chemistry, University of Regensburg, 93053 Regensburg
Prof. J. Alemán, T. Rigotti, Organic Chemistry Department, Módulo
[
1, Universidad Autónoma de Madrid, 28049 Madrid
E-mail: jose.aleman@uam.es, www.uam.es/jose.aleman
Prof. J. Alemán, Institute for Advanced Research in Chemical
Sciences (IAdChem), Universidad Autónoma de Madrid, 28049
Madrid
[
d]
†
[
]
Supporting information is given via a link at the end of the document
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Chemistry - A European Journal
10.1002/chem.201802830
COMMUNICATION
2
withdrawing (R = Br, F; 3h-j, 32-63%) groups at the acridane
core. It is also interesting to note that the steric hindered
substrate 1k (1,4-dimethyl substituted) was also well tolerated,
leading to 3k in a good 57% yield. Regarding the isocyanide
reagent, the system worked well with other alkyl groups such as
nBu (3l-m), tBu (3n-o) and benzyl (3p-q), as well as aryl (3r-s)
substituents, providing the corresponding imides in moderate to
good yields.
[
a]
Table 1. Optmization of the conditions for the oxidative Ugi reaction with 1a.
O
Ph
H
N
oxidant
catalyst
O
N
CyNC (2a)
N
additive, solvent, r.t.
1
a
3a
[
b]
2a
eq.)
t
Yield-3a
(%)
Scheme 1. Described synthesis of acridinium salts and our synthetic approach. Ent
Catalyst (mol%)
Oxidant (eq.)
[c]
(
(h)
18
18
18
[
d]
1
Cu(OTf)
Cu(OTf)
Cu(OTf)
2
2
2
(10)/bpy (30)
(10)/bpy (30)
(10)/bpy (30)
tBuOOH (1.2)
1.2
1.2
1.2
--
--
We started the optimization of the oxidative Ugi-type
[d]
2
tBuOOtBu (1.2)
reaction with N-methyl acridane (1a) as model substrate and
3
(PhCO
PhCO
(1.2)
(PhCO ) (1.2)
2
)
2
(1.2)
29
commercially available cyclohexyl isocyanide (2a) in acetonitrile
(
2
)OtBu
4
Cu(OTf)
2
(10)/bpy (30)
1.2
18
--
at room temperature (Table 1). Initially, several common
peroxides were tested as oxidants (Table 1, entries 1-4).
5
6
Cu(OTf) (10)/bpy (30)
2.0
2.0
2.0
2.0
2.0
2.0
2.0
18
4
36
2
2 2
[
e]
Unexpectedly, the use of hydroperoxides such as tBuOOH
Cu(OTf) (10)/bpy (30)
(PhCO ) (1.2)
61(66)
2
2
2
2
2
2
2
2
2
2
2
[
f]
(
TBHP) in the presence of benzoic acid as additive, which was
7
Cu(OTf)
Cu(OTf)
2
2
(10)/bpy (30)
(15)/bpy (45)
(5)/bpy (15)
(10)/bpy (30)
(PhCO
(PhCO
(PhCO
(PhCO
)
)
)
)
(1.2)
(1.2)
(1.2)
(1.5)
4
35
already described in previous oxidative Ugi reactions with
8
4
42
52
22
[
14,16]
amine-substrates,
entry 1). Similarly, the aprotic dialkylperoxide tBuOOtBu or
PhCO-OO-tBu were also unsuccessful (entries 2 and 4). Next,
our recently developed Cu(OTf) /bipyridyl/benzoyl peroxide
did not lead to the desired product 3a
9
Cu(OTf)
Cu(OTf)
[Ru(bpy)
2
4
(
10
11
2
4
[
d,g]
3
](PF
6
)
2
(1)
air, blue LEDs
18
30
2
[a] 1a (0.1-0.2 mmol), oxidant, catalyst, CyNC in MeCN (0.1 M) at the room
temperature in a sealed tube. [b] Cu(OTf)2 was pre-dried under vacuum at 60
C. [c] Isolated yields. [d] Reaction in the presence of 1.2 equiv. of PhCO
e] 2 mmol scale reaction in brackets. [f] Cu(OTf) was not pre-dried. [g] Full
3
(
BPO) oxidative system for C(sp )-H bond functionalization
°
[
2
H.
[
11a]
reactions was employed (entry 3).
In this case, the reagent
2
conversion observed after 18 h (30% conv., 3.5 h). A mixture of 3a, acridone
and acridine was obtained.
BPO had a double role as both the oxidant and the carboxylic
acid or carboxylate source. Therefore, the addition of an external
carboxylic acid was not required to obtain the imide Ugi-products
Aiming to shed some light into the mechanism of the
oxidative Ugi-reaction, several experiments were carried out
3
. Accordingly, the desired product 3a was obtained in a
promising 29% yield. However, two of the main issues of this
reaction are the low stability of the products 3 under oxidative
conditions and the competition between the desired Ugi-type
reaction and the over-oxidation of the substrate to the acridone
or the aromatic acridine. Therefore, to avoid the formation of
undesired by-products, both shorter reaction times and an
excess of isocyanide were explored. We found that the use of
two equivalents of 2a and 4 hours reaction time led to the best
results, providing 3a in a synthetically useful 61% yield, which
was improved to 66% when the reaction was scaled up 20 times
(
Scheme 2). Firstly, the N-methyl acridinium salt 1a’ was
prepared by simple oxidation of the acridane 1a with trityl
[
12a]
perchlorate.
The carbocation salt 1a’ was then enrolled in the
Ugi-type reaction with cyclohexyl isocyanide (2a) with two
different reagents: p-toluic acid (equation i-a) or sodium p-
toluate (equation i-b, Scheme 2). While no reaction was
observed with p-toluic acid, the imide derivative 3t was obtained
-
in moderate yield (39%) when p-TolCO
2
was used as the
corresponding carboxylate. The lower yield obtained compared
to the reaction with the in situ generated cationic species could
be explained due to the high instability of the stoichiometrically
employed C9-unsubstituted acridinium salt 1a’, showing the
more synthetic utility of our employed oxidative C-H
functionalization approach. Therefore, under the catalytic
conditions the reactive carbocation intermediate is formed and
present in the media in low amounts, allowing an efficient and
(
entry 6). It is important to mention that the reaction was
sensitive to moisture (entry 7), being needed anhydrous
[
17]
conditions to achieve satisfactory results. Finally, the increase
or decrease of the catalyst loading (15 or 5 vs. 10 mol%, entries
8
and 9), the increase of the oxidant (entry 10), or the use of
standard oxidative aerobic photocatalytic conditions with
Ru(bpy) ](PF (entry 11), led to significant less efficient
reactions.
With the best conditions in hand, Cu(OTf)
[
3
6 2
)
selective conversion into the desired product 3. Next,
a
competition experiment was performed between the in situ
formed benzoate from the bezoyl peroxide and an external
added carboxylic acid with a similar pKa, such as p-toluic acid
2
/bipyridyl as
catalytic system and benzoyl peroxide as oxidant in acetonitrile
at r.t. (Table 1, entry 6), the reaction with different substituted
acridanes 1 was investigated (Table 2). Acridanes with various
N-protecting groups such as methyl, benzyl and phenyl
efficiently reacted, giving the desired products 3a-c in good
yields (61-70%). The reaction also tolerated different electron
(
Scheme 2, eq. ii). The reaction involved 1.2 equivalent of
benzoyl peroxide, forming at most 2.4 equivalents of benzoic
acid/benzoate, and 1.2 equivalents of the p-toluic acid. The two
possible Ugi-type products 3a and 3t were then obtained in a
perfect statistical 2:1 ratio (3a:3t, 66:33) in a 45% overall yield.
Based on the experimental observations, a plausible reaction
2
donating (R = Me, Ph, MeO; 3d-g, 41-68%,) and electron
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Chemistry - A European Journal
10.1002/chem.201802830
COMMUNICATION
O
N
pTol
mechanism was postulated (eq. iii, Scheme 2). Consequently,
i) Carbocation Formation
CyNC 2a
(2 equiv.)
pTol-CO2H
O
N
the reaction occurs via
a copper-catalyzed radical-initiated
Cy
oxidation of the benzylic C9-position to produce the carbocation
(1.2 equiv.)
[
18]
A.
Then, the addition of the isocyanide (to form B) and
MeCN, 4h, r.t.
a)
b)
sequential attack of the in situ formed benzoate, provides the
neutral intermediate C, which rapidly undergoes an Ugi-type
rearrangement process to give the desired product 3.
ClO4-
Me
3
t, --
+
-
Ph3C ClO4
CyNC 2a
O
pTol
DCM
N
N
(
2 equiv.)
O
N
Me
Me
-
+
pTol-CO2 Na
Cy
[
a,b]
Table 2. Scope for the oxidative Ugi-multicomponent reaction.
1a
1a'
(1.2 equiv.)
MeCN, 4h, r.t.
N
Me
3
t, 39%
ii) Competition experiment
O
N
Ph
Cy
+
O
pTol
Cu(OTf)2 (10 mol%)
Bipyridyl (30 mol%)
CyNC 2a (2 equiv.)
O
N
O
N
Cy
BPO (1.2 equiv.)
pTol-CO2H (1.2 equiv.)
MeCN, r.t.
N
N
3a + 3t
66 : 33
Me
Me
Me
4
5%
iii) Proposed Mechanism
O
N
Ph
Cy
O
N
N
Me 1a
Me
3a
[Cu]
(PhCOO)2
Cy
N
O
Ph
PhCO2H
PhCO2-
PhCO2-
O
N
Cy
C
N Cy
N
N
N
Me
A
Me
B
Me
C
Scheme 2. Oxidative Ugi-reaction: Mechanistic experiments and proposal.
[
[
a] The reactions were performed in a 0.1-0.4 mmol scale in CH
b] Isolated yields after flash chromatography. PMP = p-methoxylphenyl.
3
CN (see S.I.).
commercial catalyst III. In fact, when other less oxidative
[2]
3 4 2
catalysts like [Ru(bpy) ](BF ) (E*1/2 = +0.77 V vs SCE) or
[
3]
Eosin-Y (E*1/2 = +0.83 or 1.23 vs SCE) were employed, no
conversion was found. On the contrary, the stronger oxidant
For the synthesis of the photoactive acridinium salts, the
final aromatization process was carried out for some selected
imide-acridanes with tritylperchlorate as mild hydride
abstractor in dry acetonitrile,
acridinium perchlorate salts 4 in a range from 36 to 79% yield
top, Scheme 3). The photochemical properties of the newly
[3]
catalyst III (E*1/2 = +2.18 V vs SCE) gave the lactone 6 with a
3
moderate 30% yield (equation a, Scheme 3). Outstandingly, our
designed acridinium catalysts 4 led to the lactone 6 in notable
higher yields (46-93%, see Table in S.I.) under the same
conditions and reaction time. In particular, 4a and 4b turned out
to be the optimal photo-organocatalysts, providing 6 in 83% and
[
19]
yielding the corresponding
(
obtained acridiniums were next investigated. The acridinium
salts 4 display two maximum absorption bands (355-380 nm and
9
3% yield, respectively (eq. a, Scheme 3). In order to generalize
4
20-460 nm), which depend on the substituents at the imide and
the good catalytic performance of catalysts 4, the activity of both
the parent N-methyl derivative 4a and the best catalyst 4b was
compared with the Fukuzumi´s catalyst III in different photoredox
reactions (equations b-d). Initially, oxidative transformations
such as the oxidation of alcohols to aldehydes and ketones were
explored. Acridinium catalysts such as III can oxidize primary
acridinium nitrogen-atom (top right-Scheme 3, see S.I for further
1
2
details). As a result, modifications of the substituents (R , R and
3
R ) allowed an easy tuning of the excited state properties of
these acridinium salts. Interestingly, when a methoxy substituent
2
was present (R = MeO), acridiniums 4f and 4g showed a strong
bathochromic shift of both characteristic bands up to λmax =
[21]
and secondary benzylic alcohols under oxygen atmosphere
3
80 and 460 nm. Moreover, the ground-state redox potentials of
by oxidation of the arene to its radical cation and subsequent
the catalysts were determined by cyclic voltammetry (CV) in
acetonitrile as solvent (see S.I.). The ground state reduction of
catalysts 4 occurs at low potentials (around −0.3 V vs. SCE) with
[3]
deprotonation. To our delight, after one hour the alcohol 7 was
oxidized to 8 in 28% conversion with catalyst III, whereas 4a and
4
b gave a significant improved 75% and 92% conversion,
a
relative excited state reduction potential around 2.4
showing slightly variations depending on the substituents),
which are above the values of the Fukuzumi’s photocatalyst III
V
respectively (Scheme 4, eq. a). Furthermore, the anti-
Markovnikov hydro-functionalization of alkenes, which has
extensively been studied employing mesityl acridinium type
(
[
3]
(
E
1/2 = +2.18 V vs. SCE). After obtaining these appealing
[3]
catalysts, was investigated. In the chosen case of the
results, the catalytic activity of 4 was then investigated in the
dehydrogenative lactonization of 2-phenylbenzoic acid (5) as
intermolecular hydroetherification of alkenes such as 9 with
methanol (10 equiv.), a redox-active hydrogen atom transfer
[
20]
model reaction (see the optimization Table S2 in S.I.). This
transformation is known to proceed through reductive
quenching cycle and was already reported with the Fukuzumi´s
agent such as 2-phenyl malononitrile (0.5 equiv.) was used to
a
[22]
improve the yields.
As in the previous reaction, the
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Chemistry - A European Journal
10.1002/chem.201802830
COMMUNICATION
photocatalyts 4a and 4b gave higher conversions than the
F. Garrido-Castro, M. C. Maestro, J. Alemán, Tetrahedron Lett. 2018,
5
9, 1286.
K. P. Christopher, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013,
13, 5322.
Fukuzumi´s catalyst III under the same conditions (17 h, 67 and
[
2]
9
9% vs. 33%; Scheme 4, eq. b). In addition, although acridinium
1
salts are known to be weak reductants, the reduction of the
[
[
3]
4]
N. A. Romero, D. A. Nicewicz, Chem. Rev. 2016, 116, 10075.
a) K. A. Margrey, D. A. Nicewicz, Acc. Chem. Res. 2016, 49, 1997; b) A.
J. Perkowski, D. A. Nicewicz, J. Am. Chem. Soc. 2013, 135, 10334. c)
K. Ohkubo, T. Kobayashi, S. Fukuzumi, Angew. Chem. Int. Ed. 2011,
50, 8652.
bromo-ketone derivative 11 (E1/2 = -0.49 V vs SCE) with 4 was
[
2]
also challenged. Surprisingly, excellent results were also
obtained in this type of reaction, in which the N-methyl derivative
4
a showed better results than 4b (98% vs. 66% conversion).
Moreover, both photocatalysts 4 proved again to be more active
than III (29% conversion) (Scheme 3, eq. c).
[5]
a) G. Weber, F. W. J. Teale, Trans. Faraday Soc. 1957, 53, 646-655; b)
A. C. Benniston, A. Harriman, P. Li, J. P. Rostron, H. J. van
Ramesdonk, M. M. Groeneveld, H. Zhang, J. W. Verhoeven, J. Am.
Chem. Soc. 2005, 127, 16054.
O
Ph
O
Ph
[
6]
a) T. M. Bockman, J. K. Kochi, J. Phys. Org. Chem. 1997, 10, 542; b) K.
O
N
O
N
Suga, K. Ohkubo, S. Fukuzumi, J. Phys. Chem. A 2006, 110, 3860.
R3
R3
R2
R2
+
Ph3CClO4
[7]
Even if the Ph-Acr-Me catalyst did not show radical-radical reactivity it
dry MeCN, r.t.
is subject to nucleophilic deactivation: D. Zhou, R. Khatmullin, J.
Walpita, N. A. Miller, H. L. Luk, S. Vyas, C. M. Hadad, K. D. Glusac, J.
Am. Chem. Soc. 2012, 134, 11301.
N
R1
3
Yield= 36-79%
N
R1 ClO4
4
[
8]
a) S. Fukuzumi, H. Kotani, K. Ohkubo, S. Ogo, N. Tkachenko, H.
Lemmetyinen. J. Am. Chem. Soc. 2004, 126, 1600; b) Y.-C. Lin, C.-T.
Chen, Org. Lett. 2009, 11, 4858.
Photocatalytic Reactions[a]
(
a)
III: 30%[b]
III or 4 (2 mol%)
4
a: 83%[b]
b: 93%[b]
[9]
For acridinium C-9-esters with chemiluminescence applications, see
e.g.: Browne, K. A.; Deheyn, D. D.; El-Hiti, G. A.; Smith, K.; Weeks, I. J.
Am. Chem. Soc. 2011, 133, 14637.
MeCN, O2
blue LEDs, 1 h
4
CO2H
O
O
5
7
9
6
(b)
OH
O
III: 28%
[10] For phenyl-C9-acridinium derivatives in photocatalysis, see: L. Chen, H.
Li, P. Li, L. Wang, Org. Lett. 2016, 18, 3646, and references cited
therein.
III or 4 (2 mol%)
Me
Me
4
a: 75%
MeCN, O2
blue LEDs, 1 h
4b: 92%[92%][c]
8
[
11] Selected reviews: a) C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 2011,
111, 1780; b) S. A. Girard, T. Knauber, C.-J. Li, Angew. Chem. Int. Ed.
2014, 53, 74; c) Special issue on C-H activation, Chem. Rev. 2017, 117,
8481.
(c)
Me
Br
III or 4 (5 mol%)
Me
OMe
III: 33%
4
a: 67%
DCE, MeOH
NCCHPhCN
blue LEDs, 17 h
MeO
MeO
4b: 99%[80%][c]
MeO
10
O
O
[12] a) T. Stopka, L. Marzo, M. Zurro, S. Janich, E. U. Würthwein, C. G.
Daniliuc, J. Alemán, O. García Mancheño, Angew. Chem. Int. Ed. 2015,
54, 5049. b) H. Richter, R. Fröhlich, C. G. Daniliuc, O. García
Mancheño, Angew. Chem. Int. Ed. 2012, 51, 8656; c) A. Gini, J.
Bamberger, J. Luis-Barrera, M. Zurro, R. Mas-Ballesté, J. Alemán, O.
García Mancheño, Adv. Synth. Catal. 2016, 358, 4049, and references
cited therein.
(d)
III: 29%
III or 4 (5 mol%)
H
a: 98%[56%][c]
4
DMF
4b: 66%
lutidine (2 equiv.) MeO
blue LEDs, 24 h
11
12
[
a]
Scheme 3. Comparative photocatalytic reactions with III, 4a and 4b. ( NMR-
conversions. Isolated yields. NMR yields in brackets)
[
b]
[c]
In conclusion, the designed novel imide-acridinium
organophotocatalysts 4 were prepared in a simple 2-steps
approach by a new oxidative C-H functionalization/Ugi-type
reaction of acridanes, followed by an aromatization process. The
developed oxidative Ugi reaction with benzoyl peroxide, used as
both oxidant and carboxylate source, has allowed the
introduction of a polar functional group at the C9-position.
Furthermore, the methodology is rather flexible and tolerates a
wide range of substituents. In terms of reactivity, the imide-
[
13] a) I. Ugi, R. Meyr, U. Fetzer, C. Steinbrückner, Angew. Chem. 1959, 71,
386; b) J. Alemán, S. Cabrera, C. Alvarado, Recent Advances in the
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Marqués López), John Wiley & Sons, NJ, 2015, pp. 245.
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acridiniums
4 led to a notable higher activity than the
commercially available, commonly used Fukuzumi´s catalyst in
both oxidative and reductive reactions.
[15] a) A. Baeyer, Ber. Dtsch. Chem. Ges. 1871, 4, 555. b) A. V. Dubrovskiy,
R. C. Larock, J. Org. Chem. 2012, 77, 11232. c) T. Tsudaka, H. Kotani,
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Acknowledgements
[
[
[
16] C. de Graaff, L. Bensch, M. J. van Lint, E. Ruijter R. V. A. Orru, Org.
Biomol. Chem. 2015, 13, 10108.
The Boehringer Ingelheim Stiftung (Exploration Grant), the
Deutsche Forschungsgemeinschaft (DFG), COST action
CHAOS, Spanish Government (CTQ2015-64561-R), and the
European Research Council (ERC-CG, contract number:
2
17] The Cu(OTf) catalyst was pre-dried at 50-60 °C under high vacuum for
several hours prior use.
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6
47550) are gratefully acknowledged for generous support.
[
19] (a) Alternative electrochemical oxidation: A. V. Shchepochkin, O. N.
Chupakhin, V. N. Charushin, D. V. Steglenko, V. I. Minkin, G. L.
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J. Am. Chem. Soc. 2004, 126, 17059.
Keywords: C-H functionalization • Oxidative Ugi reaction •
Acridinium salts • Photocatalysis • Multicomponent
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1]
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Chemistry - A European Journal
10.1002/chem.201802830
COMMUNICATION
COMMUNICATION
Andrea Gini, Mustafa Uygur, Thomas
Rigotti, José Alemán* and Olga García
Mancheño*
Page No. – Page No.
Novel Oxidative Ugi-Reaction for the
Synthesis of Highly Active Visible
Light Imide-Acridinium
Sweet’n Salt: The first, mild, modular, oxidative Ugi-reaction on benzylic
substrates, such acridanes, allows the development of an unprecedented family of
imide-acridinium visible light photocatalysts with boosted reactivities in both
oxidative and reductive processes.
OrganoPhotocatalysts
This article is protected by copyright. All rights reserved.