Synthesis of stilbene derivatives via visible-light-induced cross-coupling of aryl diazonium salts with nitroalkenes using-NO2 as a leaving group

Article abstract of DOI:10.1039/c6cc08182g

The straightforward visible-light-induced synthesis of stilbene compounds via the cross-coupling of nitroalkenes and diazonium tetrafluoroborates under transition-metal-free conditions is described. The protocol uses green LEDs as light sources and eosin Y as an organophotoredox catalyst. Broad substrate scope and exclusive selectivity for the (E)-configuration of stilbenes are observed. This protocol proceeds via a radical pathway, with nitroalkenes serving as the radical acceptor, and the nitro group is cleaved during the process.

Full text of DOI:10.1039/c6cc08182g

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DOI: 10.1039/C6CC08182G
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Synthesis of stilbene derivatives by visible-light-induced cross-
coupling of aryl diazonium salts with nitroalkenes with -NO2 as a
leaving group
Received 00th January 20xx,
Accepted 00th January 20xx
Na Zhang, Zheng-Jun Quan,* Zhang Zhang, Yu-Xia Da, and Xi-Cun Wang*
DOI: 10.1039/x0xx00000x
The straightforward visible-light-induced synthesis of stilbene compounds from the cross-coupling of nitroalkenes and
diazonium tetrafluoroborates under transition-metal-free conditions is described. The protocol uses green LEDs as light
sources and eosin Y as an organophotoredox catalyst. Broad substrate scope and exclusive selectivity for the (E)-
configuration of stilbenes is observed. This protocol proceeds via a radical pathway, with nitroalkenes serving as the
radical acceptor, and the nitro group is cleaved during the process.
www.rsc.org/
Stilbenes are undoubtedly one of the most important and nitroarenes as alkene sources in stilbenes formation through
widely studied classes of compounds. They have been [Ru(bpy)3]2+-catalyzed visible-light-mediated arylation with
extensively used in many fields, such as organic photochemistry, diazonium salts was reported.17 In this process, cross-coupling
and in materials, pharmaceuticals and natural compounds of nitroalkenes occurred via NO2 acting as a leaving group.
containing C-C double bonds.1 Therefore, many classical However, a limited yield of 37% was observed (Figure 1B, Z =
methodologies have been developed to synthesize stilbenes, NO2).
including the Wittig-Horner reaction,2 Julia olefination,3 and the
Perkin condensation.4 These reactions rely on the requisite
phosphonium salts, sulfone and sodium-substituted
organometallic starting materials, and the Perkin reaction
deprotection requires ultra-low temperatures. Alternatively,
the semihydrogenation of alkynes can deliver stilbenes.5
However, overcoming over-reduction and chemo-selectivity are
major challenges in this reaction. The transition-metal-
catalyzed Heck-type reaction is another powerful method for
preparing stilbenes using Pd,6 Ni,7 Co,8 Cu9 and Fe10 catalysts
(Figure 1A). However, these transition metal reagents have
limitations, such as their high price, the generation of toxic
waste, the need for an air-sensitive or expensive ligand, and a
reaction system with limited expansion of the reaction
substrate.11 From economic and environmental viewpoints, it
would be advantageous and desirable to develop transition-
metal-free systems for the synthesis of stilbenes under mild
reaction conditions. More recently, for instance, Walsh et al12 Figure 1. Synthesis of stilbene compounds.
reported an organocatalytic approach for the stilbenes
synthesis by the homo-coupling of benzyl halides, wherein tert-
butyl phenyl sulfoxide is employed as a traceless precatalyst.
Nitroalkenes are an important class of synthetic
intermediates that have been used in the preparation of a wide
variety of organic compounds,13 including biological and
pharmaceutical compounds.14-16 As a representative example,
In recent decades, photocatalysis has emerged as a powerful,
green tool in modern organic transformations due to its low
cost, ready availability and environmental friendliness.18 The
key concept of this protocol is the use of a single-electron
transfer (SET) process to generate aryl radicals from aryl
diazonium salts using a photocatalyst in the presence of visible
light.19
Despite ruthenium and iridium polypyridyl complexes are the
catalyst of choice for many photoredox reactions due to its
unique photochemical properties, they suffers from
disadvantages such as potential toxicity, low sustainability, high
cost. Organic chromophores as “metal-free” alternatives to
transition metal photocatalysts allowed access to numerous
Key Laboratory of Polymer Materials, College of Chemistry and Chemical
Engineering, Northwest Normal University, Lanzhou, Gansu 730070, P. R. China.
E-mail: wangxicun@nwnu.edu.cn; quanzhengjun@hotmail.com
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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radical reactions. Moreover, the diversity of these organic dyes eosin Y, were then evaluated (entries 2–3). IntereVsiteiwnAgrltyic,leeOonslinine
may promote unusual reactions by broadening range of Y led to the highest yield of 3a (72%) (enDtrOyI:31)0..H10o3w9/eCv6eCrC,0o8n18ly2Ga
substrates that are unreactive in most synthetic trace amount of product was detected using fluorescein (entry
methodologies.20
2). The solvent also plays an important role in this
Arenediazonium salts, which are readily available by transformation; DMF was more effective than the other tested
diazotization of anilines, have been widely utilized as a solvents (entries 4-10).
convenient aryl radical source due to their relatively high
reduction potentials. Photoredox reactions with Green LEDs (1.0 W, λ = 530
Different light sources (CFLs and blue LEDs) were tested.
10 nm) were more effective than
±
arenediazonium salts are often more selective than traditional compact fluorescent lamps (CFLs), indicating the higher
methods. It has been revealed that commercial narrow-band photocatalytic activity of eosin Y in the presence of high-
LEDs with a maximum intensity at 535 nm (green light) are intensity green light (entries 11-12). We also optimized the
efficient for the eosin Y-catalyzed heterolyze diazonium ions to reaction time; when the reaction time was reduced to 6 h, the
give highly electrophilic aryl cations.21 The catalyst eosin Y (λmax yield declined slightly to 70% (entries 13-14). The absence of
= 520 nm, E1/2red = -1.08 V) is able to reduce aryl diazonium salts, either the photocatalyst eosin Y or visible light decreased the
such as phenyldiazonium tetrafluoroborate (E1/2red = -0.06 V), to yield to 10-15%, thus suggesting that direct photocleavage of
highly reactive phenyl radicals that can subsequently be the C–N bond of arenediazonium salt might be operating as
trapped by nitroalkene.17,22
previously proven by Majek et al.21 (Table 1, entries 15 and 16).
Herein, we report the photocatalytic synthesis of stilbene
derivatives via the cross-coupling of readily available
nitroalkenes and arenediazonium salts that requires only green
light and the organic dye eosin Y as a catalyst (Figure 1C). This
transformation features high stereoselectivity and is applicable
to the preparation of various (E)-stilbene derivatives, including
key functional molecules.
Table 1 Optimization of Reaction Conditionsa,b
entry
catalyst (5
mol%)
light
source
time
(h)
24
24
24
24
24
24
24
24
24
24
24
24
12
6
yield
(%)
62
trace
72
solvent
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
eosin B
fluorescein
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
eosin Y
-
DMF
DMF
DMF
DMSO
THF
CH3CN
CH3OH
EtOH
green LED
green LED
green LED
green LED
green LED
green LED
green LED
green LED
green LED
green LED
CFLs
blue LED
green LED
green LED
green LED
-
65
Scheme 1 Scope of the diazonium salt.
trace
trace
31
25
trace
43
62
49
72
70
Using these optimized conditions, we next varied the
aryldiazonium salts used as the standard aryl radical in reactions
with nitroalkene 1a (Scheme 1). The reaction exhibited an
excellent chemoselectivity profile, tolerating a wide range of
functional groups. Aryldiazonium salts substituted with
toluene
1,4-dioxane
DMF
DMF
DMF
DMF
DMF
electron-donating (Me, MeO; 3b
(Cl, Br; 3d 3e) groups were well tolerated. Steric hindrance at
the ortho- or meta-position was also tolerated (3f 3l). In
, 3c) and electron-withdrawing
,
-
24
24
10
15
addition to its mild, base-free nature, an important feature of
the photoredox catalytic system is its compatibility with
halogenated substrates. In contrast to palladium-catalyzed
Heck coupling, this system does not generally undergo
conventional oxidative addition to aryl halides. As such, the
eosin Y
DMF
aReaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), catalyst (5.0 mol %),
solvent (1.0 mL), rt, air atmosphere. bIsolated yield.
To commence our investigation, the reaction of nitroalkene
1a with diazonium salt 2a was performed using 5 mol % eosin B
as a photocatalyst under irradiation with green LEDs [1.0 W, λ =
brominated, iodinated stilbene compounds 3d-3e, 3h-3j and 3l,
obtained from 1a and chloro-, bromo- and iodo-substituted
aryldiazonium salts, respectively, were isolated with high yields
using this method without competitive cleavage of the C-X bond
(X = Cl, Br, I). These synthesized compounds provide a synthetic
530
±10 nm] in open air (Table 1). The reaction proceeded and
produced the desired coupling product 3a with a 62% yield
(entry 1). A range of photocatalysts, including fluorescein and
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handle for further functionalization. Additionally, di-substituted
diazonium salt in this coupling reaction produced product 3m
with 65% yield. Moreover, N,N-diethylaminophenyl- and
naphthyl-substituted diazonium salts produced good yields of
products 3n (77%) and 3o (83%), respectively. Thus, various
substituted arenediazonium salts can be used in this coupling
reaction to give their corresponding stilbene compounds.
We next varied the nitroalkene and aryldiazonium salt
reaction components (Scheme 2). A number of nitroalkenes
with halo-substituted phenyldiazonium salts were efficiently
transformed into the desired products 6a-6j under standard
reaction conditions, including adding electron-rich (Me and
MeO) and electron-deficient (F, Cl, Cl and Br) groups to the
aromatic ring. Dichloro nitroalkene was incorporated into
product 6k with a 78% yield. It was also possible to use
heterocyclic nitroalkenes with various diazonium salts to deliver
furan-functionalized (6l-6n) and thiophene-functionalized (6o-
6p) stilbene compounds. We found that conjugated-diene
nitroalkenes could be effectively combined with aryl diazonium
salts to give the expected 1,4-diphenylbuta-1,3-diene 6q-6r in
57-62% yields, thus offering opportunities for pharmaceutical
and material intermediates.
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DOI: 10.1039/C6CC08182G
Figure 2 Control experiments.
Combining the observations described above, we propose
the mechanism shown in Figure 3 to rationalize this reaction.
Initially, the aryl radical
state of eosin Y to aryldiazonium salt
A
is formed by SET from the excited
, which is trapped by the
to generate the β-nitro radical (a radical Michael
into is also possible). The β-nitro radical is
by two possible
pathways: (a) oxidation of the radical intermediate by the
, assisting in the elimination of
by the aryl diazonium salt in a
1
nitroalkene
addition of
1
A
B
1
B
further transformed into coupling product
3
B
eosin Y radical cation to give
NO2;23 or (b): the oxidation of
3
A
radical chain-transfer mechanism.
Figure 3 Proposed mechanism.
In summary, we have developed an efficient, simple and
practical method to synthesize stilbene compounds by
photocatalytic coupling. The aryl diazonium salts were
converted to aryl radicals that are then trapped by the
nitroalkene, and the nitro group is cleaved in a sequential
elimination. The procedure is experimentally simple and
characterized by high yields, low catalyst loading and mild
conditions using green LEDs. The reaction scope comprises a
wide range of substituted aryl diazonium salts and tolerates a
variety of functionalized nitroalkenes.
Scheme 2 Substrate scope of stilbene.
To gain insight into the reaction mechanism, we conducted
further mechanistic investigations. The reaction between p-
chlorobenzene diazonium tetrafluoroborate and 2,2,6,6-
tetramethylpiperidinoxyl (TEMPO) gave 1-(4-chlorophenoxy)-
2,2,6,6-tetramethylpiperidine
7 in an 88% yield (Figure 2). No
desired product was detected from the reaction of 1a with the
same diazonium salt in the presence of TEMPO as a radical
scavenger or 2,6-ditertbutyl-4-methylphenol (BHT) as a radical
inhibitor, suggesting that the reaction proceeds via a radical
pathway.
Acknowledgements
We are thankful for financial support from the National Natural
Science Foundation of China (Nos. 21362032, 21362031 and
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