Phenanthrene synthesis by eosin Y-catalyzed, visible light- Induced [4+2] benzannulation of biaryldiazonium salts with alkynes

Article abstract of DOI:10.1002/adsc.201200569

A metal-free, visible light-induced [4+2] benzannulation of biaryldiazonium salts with alkynes was developed. With eosin Y as photoredox catalyst, a variety of 9-substituted or 9,10-disubstituted phenanthrenes were obtained via a cascade radical addition and cyclization sequence. Copyright

Full text of DOI:10.1002/adsc.201200569

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DOI: 10.1002/adsc.201200569
Phenanthrene Synthesis by Eosin Y-Catalyzed, Visible Light-
Induced [4+2]Benzannulation of Biaryldiazonium Salts with
Alkynes
Tiebo Xiao,a Xichang Dong,a Yanchi Tang,a and Lei Zhoua,*
a
School of Chemistry and Chemical Engineering, Sun Yat-Sen University, 135 Xingang West Road, Guangzhou 510275,
Peopleꢀs Republic of China
Fax : (+86)-20-8411-0217; phone: (+86)-20-8411-0217; e-mail: zhoul39@mail.sysu.edu.cn
Received: June 29, 2012; Revised: September 3, 2012; Published online: November 8, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200569.
À
Abstract: A metal-free, visible light-induced [4+
2]benzannulation of biaryldiazonium salts with alk-
light-induced C H bond arylation of heteroarenes
with aryldiazonium salts.[11]
A
Phenanthrenes are important organic compounds
with wide range of applications in medicinal chemis-
try[12] and material sciences.[13] The classical method to
synthesize phenanthrene derivatives is the photocycli-
zation of stilbenes.[14] Cycloisomerization of arynes
with unsaturated compounds,[15] the connection of two
aromatic rings through cross-coupling followed by in-
tramolecular cyclization[16] are also frequently utilized
for the synthesis of phenanthrenes. Recently, the tran-
sition metal-catalyzed [4+2]benzannulation of biaryl
compounds with alkynes, which allows the creation of
catalyst, a variety of 9-substituted or 9,10-disubsti-
tuted phenanthrenes were obtained via a cascade
radical addition and cyclization sequence.
Keywords: alkynes; benzannulation; diazonium
salts; phenanthrenes; visible light
Aryldiazonium salts are precursors that can efficiently a series of phenanthrenes through direct activation of
[17]
À
generate aryl radicals via the homolytic dediazonia- C H bonds, has attracted much attention. The use
+ [1]
tion of ArN2 . The established dediazoniation meth- of biaryldiazonium salts as substrates provides an al-
ods include: (i) organic reduction at an electrode; (ii) ternative route for the synthesis of phenanthrenes via
radiation from solvated electrons generated in water; a radical reaction. In 1988, Zanardi and co-workers
(iii) photo-induced electron transfer; (iv) reduction by reported an intermolecular cycloaddition of biphenyl-
metal cations; (v) induction using an anion; (vi) sol- diazonium salts with mono-substituted acetylenes in
vent-induced dediazoniation with the solvent serving pyridine,[18] in which the aryl radicals were generated
as the electron donor.[2] Although the radical reaction through the decomposition of azo-type adducts of di-
by photochemical decomposition of diazonium salts is azonium salts and pyridine.[19] Although the scope of
clean and cost-effecient,[3] there is often competition this reaction was limited and yields of phenanthrenes
with the reaction in which the aryl cation is formed.[4] were rather low due to the side reactions, this seminal
Moreover, the energy-consuming UV radiation is gen- work indicates that a cascade radical addition and
erally required for these photochemical transforma- cyclization is indeed possible for the synthesis of phe-
tions.[5] Visible-light in combination with a photoredox nanthrenes. Herein we wish to report an eosin Y-cata-
catalyst provides an environmentally friendly method lyzed, visible light-induced [4+2]benzannulation be-
to access free radical intermediates that can be used tween biaryldiazonium salts and alkynes, which allows
in various chemical reactions.[6] Diazonium salts act as the assembly of various 9-substituted and 9,10-disub-
oxidative quenchers in photoredox chemistry,[7] which stituted phenanthrenes under mild conditions.
was first applied by Deronzier in the visible light-
Initially, a 1:1 mixture of biphenyldiazonium salt 1a
mediated Pschorr reaction[8] and oxidation of benzyl and methyl propiolate 2a was irradiated with a 24-W
alcohol.[9] A recent report by Sanford demonstrated fluorescent bulb for 12 h in the presence of 1 mol%
À
a Pd-catalyzed room temperature C H arylation reac- of eosin Y (3) at room temperature. To our delight, it
tion using aryldiazonium salts under visible light pho- afforded the desired phenanthrene 4aa in 25% yield
toredox conditions.[10] In addition, organic dyes have (Table 1, entry 1). The use of an excess of 2a resulted
also been used as inexpensive photocatalyts in visible in higher yield and the best ratio of 1a to 2a is 1:5
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Table 1. Optimization of the reaction conditions.[a]
Entry
Conditions
Yield[b]
1
2
3
4
5
6
7
8
2a (1 equiv.), MeCN
2a (3 equiv.), MeCN
2a (5 equiv.), MeCN
2a (10 equiv.), MeCN
2a (5 equiv.), DMSO
2a (5 equiv.), DMF
2a (5 equiv.), NMP
2a (5 equiv.), dioxane
2a (5 equiv.), THF
2a (5 equiv.), toluene
2a (5 equiv.), MeCN, NEt3 (2 equiv.)
2a (5 equiv.), MeCN, t-BuOLi (2 equiv.)
2a (5 equiv.), MeCN, no light
2a (5 equiv.), MeCN, no catalyst
2a (3 equiv.), MeCN
25%
53%
71%
72%
46%
31%
25%
20%
12%
6%
37%
50%
Trace
Trace
74%
9
10
11
12
13
14
15[c]
[a]
All the reactions were carried out with biphenyldiazonium salt 1a (0.2 mmol), methyl propiolate 2a and eosin Y
(1 mol%) in 0.6 mL of solvent at room temperature with irradiation using a 24-W fluorescent bulb for 12 h.
Yield was determined by H NMR with MeNO2 as internal standard.
1a was added in batches (0.04 mmol every hour).
[b]
[c]
1
(Table 1, entries 2–4). The benzannulation was found electron-donating character. These results indicated
to proceed better in polar solvents, with MeCN giving that the addition of a radical to electron-deficient alk-
the most desirable result (Table 1, entries 4–7). The
ACHTUNGTRENyNGNU nes is more favourable. 2-Ethynylpyridine can also
observed low yields of the reactions in less polar sol- be used as a substrate in this reaction, affording the 9-
vents may be attributed to the poor solubility of the (2-pyridyl) phenanthrene 4ak in 51% yield (Table 2,
diazonium salts in these solvents (Table 1, entries 8– entry 11). The [4+2]benzannulation between biphe-
10). Diminished yields were obtained when NEt3 and nyldiazonium salt 1a and 4-phenyl-1-butyne gives the
t-BuOLi were used, which was perhaps caused by the phenanthrene 4al in 47% yield (Table 2, entry 12).
direct reaction of base with 1a. In the control experi- Additionally, internal alkynes also reacted smoothly
ments, trace amounts of the products were detected with 1a, leading to the formation of the corresponding
in the absence of either light or the catalyst (Table 1, 9,10-disubstituted phenanthrenes in moderate yields
entries 13 and 14). Strikingly, the yield of 4aa was in- (Table 2, entries 13–16). In the case of 1,4-diphenylbu-
ꢀ
creased to 74% by addition of diazonium salt 1a grad- tadiyne, only one C C bond reacted, which afforded
ually. Moreover, the amount of 2a could be reduced the phenylethynyl-substituted phenanthrene 4ap in
to 3 equiv. using this method (Table 1, entry 15).
With the optimized reaction conditions in hand, the
a yield of 59% (Table 2, entry 16).
In the next step, we chose methyl propiolate as the
scope of this transformation was studied by using bi- substrate for the benzannulation with various biaryl-
phenyldiazonium salts 1a and various alkynes. As diazonium salts. As shown in Table 3, the reaction tol-
shown in Table 2, the reaction proceeded smoothly erates various functional groups including methyl,
with a series of terminal arylalkynes (Table 2, en- chloro, trifluoromethyl, phenyl and methoxy in the bi-
tries 2–10). Various functional groups including phenyldiazonium salts (Table 3, entries 1–5). In addi-
chloro, fluoro, ester, ketone, nitro and methoxy are tion, we did not find any dehalogenated product from
tolerated under the chosen reaction conditions. A the radical reactions involving a chlorine functionality
higher electron-withdrawing character of the substitu- (Table 3, entry 2). The reaction also worked smoothly
ents on the aromatic ring of the alkynes resulted in when only one ortho hydrogen atom was available in
higher yields compared to substituents with a more the biaryldiazonium salts, however, the product was
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Phenanthrene Synthesis by Eosin Y-Catalyzed, Visible Light-Induced [4+2]Benzannulation
Table 2. Reaction scope of alkynes.[a] Table 3. Reaction scope of biaryldiazonium salts.[a]
Entry
R1
R2
Product
Yield[b]
1
2
3
4
5
6
7
H
H
H
H
H
H
H
H
H
H
H
H
CO2Et
Ph
Ph
Ph
CO2Me
Ph
4aa
4ab
4ac
4ad
4ae
4af
4ag
4ah
4ai
4aj
4ak
4al
4am
4an
4ao
4ap
67%
60%
55%
49%
32%
63%
81%
71%
64%
66%
51%
47%
57%
55%
42%
59%
p-Me-C6H4
m-Me-C6H4
p-OMe-C6H4
p-Cl-C6H4
p-F-C6H4
p-CO2Me-C6H4
p-COCH3-C6H4
p-NO2-C6H4
2-pyridyl
8[c]
9[c]
10[c]
11
12
13
14
15[c]
16[c]
CH2CH2Ph
CO2Et
CO2Et
COPh
ꢀ
C CPh
[a]
All the reactions were carried out with biphenyl diazoni-
um salt 1a (0.3 mmol), alkynes (3 equiv,) and eosin Y
(1 mol%) in 0.6 mL MeCN at room temperature with the
irradiation of a 24-W fluorescent bulb for 12 h; 1a was
added in six portions (0.05 mmol per every hour).
Isolated yield.
[b]
[c]
1.6 mL of MeCN were used.
obtained in a lower yield (Table 3, entries 6 and 7).
When two non-equivalent ortho-hydrogen atoms were
available, two regioisomers were obtained and the
product with the least steric hindrance predominates
(Table 3, entry 8). The biaryldiazonium salts 1j, 1k, 1l
underwent reaction with methyl propiolate to give the
corresponding 9-substituted phenanthrenes 4ja, 4ka,
4la in yields of 77%, 62% and 65% respectively. The
structure of 4la was confirmed by X-ray crystal dif-
fraction.[20] Gratifyingly, we found that 2-(2-thienyl)-
phenyldiazonium salt also reacts in this annulation re-
action to generate a heteroaromatic system (Table 3,
entry 12).
[a]
Reaction conditions: biaryldiazonium salts 1 (0.3 mmol),
methyl propiolate (3 equiv.) and eosin Y (1 mol%) in
0.6 mL MeCN at room temperature with the irradiation
of a 24-W fluorescent bulb for 12 h; diazonium salt was
added in six batches (0.05 mmol per every hour).
Isolated yield.
10 equiv. of methyl propiolate were used.
Total yields of 4ia and 4ia’, the ratio was calculated on
the basis of the isolated yields of these two compounds.
A plausible mechanism for this visible light-induced
[4+2]benzannulation is described in Scheme 1. First-
ly, photoexcitation of eosin Y by visible light gener-
ates excited eosin Y*. Then a biaryl radical is formed
via single-electron-transfer (SET) from the diazonium
[b]
[c]
[d]
salt 1 and concomitant oxidation of eosin Y* to eosin
+ [8–11]
YC .
The addition of the biaryl radical to alkyne lyst and forms the cation intermediate D. Lastly, de-
generates the vinyl radical B, followed by an intramo- protonation of D leads to the desired phenanthrene 4.
lecular radical cyclization to give the cyclized radical In conclusion, we have developed an eosin Y-cata-
intermediate C. A single-electron oxidation of C by lyzed, visible light-induced [4+2]benzannulation of
the eosin Y radical cation regenerates the photocata- biaryldiazonium salts with alkynes. A wide range of
Adv. Synth. Catal. 2012, 354, 3195 – 3199
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Tiebo Xiao et al.
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Scheme 1. Plausible mechanism.
functional groups can be tolerated in the reaction
conditions proposed. Various 9-substituted and 9,10-
disubstituted phenanthrenes were assembled via cas-
cade radical addition and cyclization. This study
opens up possibilities for developing new reactions
based on visible light-induced sequential radical reac-
tions. Further investigations on this type of photo-re-
action are ongoing in our lab and the results will be
reported in due course.
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Induced [4+2]Benzannulation of Biaryldiazonium
Salts with Alkynes
In a 10-mL snap vial were placed eosin Y (1 mol%, 2 mg),
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Financial support from NSFC (Grant No. J1103305), Sun
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