Intermolecular [2+2] Photocycloaddition of β-Nitrostyrenes to Olefins upon Irradiation with Visible Light

Article abstract of DOI:10.1055/s-0036-1588524

The title compounds were found to undergo a [2+2] photocycloaddition with olefins at λ = 419 nm in CH ₂ Cl ₂ as the solvent. The resulting cyclobutanes were isolated in yields of 32-87% (11 examples) and showed a defined relative configuration at C1/C4 in the major diastereoisomer (nitro and aryl trans). The analysis of side products and triplet sensitization experiments support a mechanistic scenario in which a 1,4-diradical is formed as a key intermediate.

Full text of DOI:10.1055/s-0036-1588524

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Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
letter
A
en
L.-M. Mohr, T. Bach
Letter
Synlett
Intermolecular [2+2] Photocycloaddition of β-Nitrostyrenes to
Olefins upon Irradiation with Visible Light
Lisa-Marie Mohr
Thorsten Bach*
0
0
0
0
0-
0
0
2
1-
3
4
2
0-
2
0
2
hν (λ = 419 nm)
c = 20 mM (CH2Cl2)
r.t., t = 2–24 h
R1
Ar
R1
R3
R2
R4
1
4
Department Chemie and Catalysis Research Center (CRC),
Technische Universität München, 85747 Garching, Germany
thorsten.bach@ch.tum.de
Ar
R2
R3
+
11 examples
O2N
O2N
R4
32–87%
Dedicated to Victor Snieckus, a dear colleague and friend, on
the occasion of his 80th birthday
Received: 19.06.2017
Accepted after revision: 30.06.2017
Published online: 31.08.2017
dergo direct intermolecular [2+2] photocycloaddition reac-
tion upon excitation with visible light and we report in this
communication on our preliminary results on this topic.
Already in the 19th century, the [2+2] photodimeriza-
tion of trans-β-nitrostyrene was observed to occur upon
exposure to sunlight.11 However, reactions with olefins in
the spirit of an intermolecular [2+2] photocycloaddition
have remained rare and were performed exclusively with
short-wavelength light. Chapman et al. mentioned in a re-
view on the photochemistry of unsaturated nitro com-
pounds the reaction with olefins but did not provide any
experimental details.12,13
DOI: 10.1055/s-0036-1588524; Art ID: st-2017-r0492-l
License terms:
Abstract The title compounds were found to undergo a [2+2] photo-
cycloaddition with olefins at λ = 419 nm in CH2Cl2 as the solvent. The
resulting cyclobutanes were isolated in yields of 32–87% (11 examples)
and showed a defined relative configuration at C1/C4 in the major dia-
stereoisomer (nitro and aryl trans). The analysis of side products and
triplet sensitization experiments support a mechanistic scenario in
which a 1,4-diradical is formed as a key intermediate.
Key words cycloaddition, cyclobutanes, diastereoselectivity, nitro
compounds, photochemistry, stereoselective synthesis, umpolung, visi-
ble light
hν (λ > 250 nm)
H
Ph
Ph
r.t. (PhH)
+
78%
O2N
O2N
H
Although [2+2] photocycloaddition chemistry1 origi-
nates historically2 from experiments performed with visi-
ble light, the advent of artificial UV light sources led – start-
ing in the middle of the 20th century – to the almost exclu-
sive use of short-wavelength (λ = 250–380 nm) irradiation
in all areas of photochemistry. Interest in reactions that
were promoted by long-wavelength (λ > 380 nm) irradia-
tion was spurred in the 1970s and in the 1980s by the de-
sire to find suitable energy storage systems mainly based
on the [2+2] photocycloaddition of norbornadienes to
quadricyclenes.3 Aromatic carbonyl compounds4 and tran-
sition-metal salts5 were found to act as triplet sensitizers in
this transformation allowing the reaction to occur with vis-
ible light. More recently, triplet energy sensitization has
been employed for enantioselective6 [2+2] photocycloaddi-
tion reactions that are promoted by visible light7 in the
presence of an appropriate sensitizer.8 In the context of our
work on the activation of chromophors by Lewis or Brønsted
acids,9 we became interested in the photochemistry of ni-
trostyrenes.10 The compound class seemed amenable to un-
1
2a
3a
Scheme 1 [2+2] Photocycloaddition of trans-β-nitrostyrene (1) and in-
dene (2a) as reported by Majima et al.14
Later, Majima et al. employed the reaction of trans-β-ni-
trostyrene (1) and indene (2a) to form cyclobutane 3a
(Scheme 1).14 A high-pressure mercury lamp was employed
as the light source in this transformation. In more recent
work, pyrex-filtered irradiation was used to study the reac-
tion of nitrostyrenes with silyl enol ethers.15,16
Inspection of the UV-Vis spectrum17 of trans-β-nitrosty-
rene in CH2Cl2 (Figure 1) reveals a strong absorption cen-
tered at λ = 312 nm (ε = 16500 M–1 cm–1). This band has
been previously assigned to an allowed ππ*-transition with
significant charge-transfer character.18,19 At high concentra-
tion it is evident that the absorption continues into the visi-
ble region of the electromagnetic spectrum in line with the
fact that trans-β-nitrostyrene (1) is a yellow-colored solid.
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

B
L.-M. Mohr, T. Bach
Letter
Synlett
Further experiments were undertaken to identify a less
problematic solvent but benzene and to optimize the reac-
tion conditions at λ = 419 nm. While toluene was found less
suited to substitute benzene, dichloromethane turned out
to be an excellent solvent. A larger excess of the olefin led to
higher product yields and the concentration was lowered to
20 mM in order to allow for small-scale reactions with
more precious, not commercially available nitrostyrenes
(vide infra). At optimized conditions21 the [2+2] photocy-
cloaddition products 3a/3a′ were obtained in a yield of 87%
after 24 hours of irradiation at λ = 419 nm. A variety of oth-
er olefins was employed in the reaction, and the results are
summarized in Scheme 2.
Figure 1 UV-Vis spectrum of trans-β-nitrostyrene in CH2Cl2 solution
(c = 0.05 mM), the inset shows the long-wavelength absorption measured
at c = 5 mM
In view of the apparent long-wavelength absorption of
trans-β-nitrostyrene (1), its reaction with indene was revis-
ited. The concentration, the solvent, and the stoichiometry
(3.1 equiv indene) were taken from previous work,14 and
the reaction was run for 23 hours (Table 1). We were
pleased to find that conversion was not only complete
when the mixture was irradiated with fluorescent lamps20
at λ = 300, 350, and 366 nm, but also at λ = 419 nm (Table 1,
entries 1–4). In all cases, it was observed that major diaste-
reoisomer 3a was accompanied by a minor diastereoisomer
to which structure 3a′ was assigned based on NOESY exper-
iments. The diastereomeric ratio (d.r.) varied at around 3:1.
Best yields were recorded at λ = 350 nm (Table 1, entry 2)
and λ = 419 nm (Table 1, entry 4). Clearly, the [2+2] photo-
cycloaddition was promoted by visible light as even long-
wavelength light-emitting diodes (LEDs) led to a significant
conversion at λ = 457 nm and at λ = 470 nm (Table 1, entries
5, 6). At λ = 517 nm, there was essentially no conversion af-
ter 23 hours (Table 1, entry 7).
R1
hν (λ = 419 nm)
c = 20 mM (CH2Cl2)
r.t., t = 6–24 h
Ph
R1
R3
R2
R4
1
R2
R3
1
+
4
O2N
2
R4
3
Ph
OEt
Ph
Ph
Ph
Ph
1
2
4
3
O2N
O2N
O2N
O2N
3a/3a' (87%)
3b/3b' (43%)
3c/3c' (52%)
3d/3d' (75%)
d.r. = 72:28
d.r. = 58:42
d.r. = 54:46
d.r. = 51:49
H
H
Ph
Ph
Ph
1
O
2
4
3
O2N
O2N
O2N
3g (51%)
3f (36%)
3e (59%)
Scheme 2 Visible-light-induced [2+2] photocycloaddition of various
olefins 2 to trans-β-nitrostyrene (1)
It should be noted that the reactions were not always
complete and that in some cases substantial amounts (up to
22%) of starting material were recovered, mostly as cis-β-
nitrostyrene. Yields refer to isolated products, however, and
are not corrected for conversion. With olefins 2b,d,f,g, the
fact that the polarity of the excited state is opposite to the
ground state polarity (photochemical umpolung) becomes
particularly apparent. C–C bond formation occurs formally
between two – in the ground state – electrophilic centers
(C1–C2) and between two nucleophilic centers (C3–C4).
The reactions with olefins 2b–d led to a mixture of diaste-
reoisomers the relative configuration of which could be in
most cases elucidated by NOESY experiments (see Support-
ing Information for further details). Cyclobutanes 3e–g
were obtained as single products. For the reaction of the
electron rich olefin 2b, it was checked that there was no re-
action in the absence of irradiation.22
Table 1 Conversion, Yield, and Diastereomeric Ratio in the Intermo-
lecular [2+2] Photocycloaddition Reaction to Products 3a/3a′ in Cor-
relation to the Irradiation Wavelength
hν (λ)
c = 100 mM (PhH)
r.t., t = 23 h
H
Ph
1
+
2a
3a
+
O2N
3a'
H
Entry
λ (nm)a
Conv. (%)
Yield (%)b
d.r. (3a/3a′)c
1
2
3
4
5
6
7
300
350
366
419
457
470
517
100
100
100
100
71
49
83
64
75
50
18
77:23
80:20
77:23
75:25
75:25
73:27
–
42
d
<5
–
Contrary to unsaturated hydrocarbons 2e and 2g, cyclo-
pentene 2h did not react with a sufficient rate at λ = 419
nm. The [2+2] photocycloaddition could, however, be suc-
cessively conducted if nitrostyrene 1 was irradiated in a
a For the emission spectra of the light sources, see ref.20
b Yield of isolated products 3a and 3a′ as a mixture of diastereoisomers.
c The diastereomeric ratio (d.r.) was determined by integration of appropri-
ate 1H NMR signals.
d No significant amounts of the respective products were isolated.
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

C
L.-M. Mohr, T. Bach
Letter
Synlett
Mechanistically, there is no indication for a reaction
course which would deviate from the pathway of typical
[2+2] photocycloaddition reactions.1 In this regard, it seems
likely that olefin 2 adds to the excited substrate, for exam-
ple, trans-β-nitrostyrene (1), most likely on the triplet hy-
persurface (Scheme 5). A 1,4-diradical 6 is formed as inter-
mediate which collapses after intersystem crossing to prod-
uct 3. Evidence for the postulated structure of diradical 6 is
based on the constitution of the products and side prod-
ucts. Indeed, olefins such as 8 were isolated in a few in-
stances and their formation is readily explained by a hydro-
gen abstraction in the intermediate 1,4-diradical. In the re-
action of olefin 2e with styrene 4c, byproduct 8 was
obtained in 5% yield and is putatively formed via intermedi-
ate 7.
H
H
H
Ph
Ph
hν (λ = 350 nm)
c = 100 mM
r.t., t = 24 h
+
+
1
O2N
H
O2N
57%
2h
3h
d.r. = 87:13
3h'
Scheme 3 Intermolecular [2+2] photocycloaddition of cyclopentene
(2h) to trans-β-nitrostyrene (1)
solution of cyclopentene at λ = 350 nm (Scheme 3). The
products were found to be a mixture of diastereoisomers in
which product 3h with the nitro group in exo position to
the cyclopentyl ring prevailed (d.r. = 87:13).
Some preliminary experiments were conducted with
other aromatic nitroolefins 4 (Scheme 4). 2,3-Dimethyl-2-
butene (2e) was employed as the reaction partner since its
use avoids the formation of regio- or diastereomeric cy-
clobutane products. It was found that electron-rich aryl
groups (para-tolyl, para-anisyl, 2-thiophenyl) in 2-position
of the respective nitroethenes (4a,23 4b,23 4d24) led in their
[2+2] photocycloaddition to results similar to those of
trans-β-nitrostyrene. Reaction times were short (2–4 h)
and cyclobutanes 5a, 5b, and 5d were obtained in yields of
50–54%. The reaction with the para-cyano-substituted ni-
trostyrene 4c25 was less chemoselective and gave product
5c in a yield of only 32% after a longer reaction time (6 h). A
side product could be isolated (vide infra).
hν, addition to
R1
R3
R1
R2
Ph
Ph
O2N
R2
R4
R4
2
3
O2N
R3
1
6
H
NC
NC
O2N
O2N
7
8
hν (λ = 419 nm)
c = 20 mM (CH2Cl2)
r.t., t = 2–6 h
Scheme 5 Mechanistic suggestion for the reaction of trans-β-nitrosty-
rene (1) with olefins 2 via triplet 1,4-diradical 6 and formation of side
product 8 in the reaction between 4c and 2e via 1,4-diradical 7
Ar
Ar
+
O2N
O2N
4
2e
5
Further support for the hypothesis that the reaction
proceeds via a triplet intermediate was obtained from the
reaction of styrene 1 and olefin 2e. In the absence of an ad-
ditive the reaction was complete after 12 hours (Scheme 2),
while a significant rate increase was noted upon addition of
the triplet sensitizer 9H-thioxanthen-9-one (thioxan-
thone).28 No β-nitrostyrene was detected after three hours
and product 3e was obtained in 47% yield (Scheme 6).
MeO
NC
S
O2N
O2N
5b (52%)
O2N
O2N
5a (54%)
5c (32%)
5d (50%)
Scheme 4 Visible-light-induced [2+2] photocycloaddition of some 2-
aryl-substituted nitroethenes 4 and 2,3-dimethyl-2-butene (2e)
hν (λ = 419 nm)
10 mol% TXT
c = 20 mM (CH2Cl2)
Ph
Ph
r.t., t = 3 h
+
If 2,3-dimethyl-2-butene was subjected to [2+2] photo-
cycloaddition with cis-β-nitrostyrene instead of trans-β-ni-
trostyrene the reaction was slower. The reaction product
was exclusively the trans-substituted cyclobutane 3e that
was isolated in 43% yield. Irradiation of trans-β-nitrosty-
rene at λ = 419 nm in the absence of an olefin established
an equilibrium26 between the cis and the trans diastereoiso-
mer in a ratio of 86:14.27 This finding is in accord with the
higher extinction coefficient of the trans diastereoisomer
within the wavelength range of the light source.20c The ab-
sorption maximum of cis-β-nitrostyrene is centered at λ =
309 nm (ε = 5200 M–1 cm–1) in CH2Cl2 solution.26b
O2N
O2N
47%
1
2e
3e
Scheme 6 Rate increase of the reaction between trans-β-nitrostyrene
(1) and 2e in the presence of a triplet sensitizer (TXT = thioxanthone)
In summary, we have shown that nitro-substituted cy-
clobutanes can be accessed by a visible-light-induced [2+2]
photocycloaddition of various 2-arylnitroethenes and ole-
fins. The yields are moderate to good (32–87%) and can pos-
sibly be further improved by adjusting the wavelength and
the reaction temperature. Given the straightforward reduc-
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

D
L.-M. Mohr, T. Bach
Letter
Synlett
tion of nitro compounds to amines,11c,14,29 the method offers
also access to various aminocyclobutanes. Mechanistically,
it remains open to what degree a charge transfer30 occurs
upon encounter of the photoexcited nitro compound and
the olefin. In addition, it might be worth to study whether
other nitroethenes but nitrostyrenes are equally suited for
[2+2] photocycloaddition reactions. Work along these lines
is in progress in our laboratories and will be reported in due
course.
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(b) Tröster, A.; Alonso, R.; Bauer, A.; Bach, T. J. Am. Chem. Soc.
2016, 138, 7808. (c) Blum, T. R.; Miller, Z. D.; Bates, D. M.; Guzei,
I. A.; Yoon, T. P. Science 2016, 354, 1391.
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Ed. 2017, 56, 4337.
(10) Reviews on the photochemistry of nitro compounds: (a) Ho, T.-
I.; Chow, Y. L. Photochemistry of Nitro and Nitroso Compounds, In
The Chemistry of Functional Groups, Supplement F2: The Chemis-
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Funding Information
Financial support by the European Research Council under the Euro-
pean Union’s Horizon 2020 research and innovation programme
(grant agreement No 665951 – ELICOS) is gratefully acknowledged.
H
2
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2
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a
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i
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I
O
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/
6
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5
9
5
1)
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1588524.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(13) In a later paper, the reaction of trans-β-nitrostyrene (1) and 2,3-
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300 nm: Magner, J. T.; Selke, M.; Russell, A. A.; Chapman, O. L.
J. Chem. Ed. 1996, 73, 854.
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1996, 939.
Primary Data
for this article are available online at http://www.thieme-con-
nect.com/products/ejournals/journal/10.1055/s-00000083 and
can be cited using the following DOI: 10.4125/pd0095th.
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riarDyat
P
m
riarDyat
1
04.1
2
5
p/
d
0
0
8
8
ht2.0
1
7-03-0
7
Z
a
heln
1
C
h
e
mstiry
(16) For a Cr-photocatalytic [4+2] cycloaddition of trans-β-nitro-
para-methoxystyrene and 1,3-dienes, see: Stevenson, S. M.;
Higgins, R. F.; Shores, M. P.; Ferreira, E. M. Chem. Sci. 2017, 8,
654.
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R. I.; Fel'gendler, A. V.; Berkova, G. A.; Berestovitskaya, V. A. Russ.
J. Gen. Chem. 2008, 78, 1711.
References and Notes
(1) Poplata, S.; Tröster, A.; Zou, Y.-Q.; Bach, T. Chem. Rev. 2016, 116,
9748.
(2) Roth, H. D. Angew. Chem., Int. Ed. Engl. 1989, 28, 1193.
(3) (a) Lennartson, A.; Roffey, A.; Moth-Poulsen, K. Tetrahedron Lett.
2015, 56, 1457. (b) Dubonosov, A. D.; Bren, V. A.; Chernoivanov,
V. A. Russ. Chem. Rev. 2002, 71, 917.
(4) (a) Barwise, A. J. G.; Gorman, A. A.; Leyland, R. L.; Smith, P. G.;
Rodgers, M. A. J. J. Am. Chem. Soc. 1978, 100, 1814. (b) Jones, G.
II.; Chiang, S.-H.; Xuan, P. T. J. Photochem. 1979, 10, 1.
(5) (a) Ikezawa, H.; Kutal, C.; Yasufuku, K.; Yamazaki, H. J. Am.
Chem. Soc. 1986, 108, 1589. (b) Grutsch, P. A.; Kutal, C. J. Am.
Chem. Soc. 1986, 108, 3108. (c) Sluggett, G. W.; Turro, N. J.; Roth,
H. D. J. Phys. Chem. A 1997, 101, 8834.
(6) (a) Brimioulle, R.; Lenhart, D.; Maturi, M. M.; Bach, T. Angew.
Chem. Int. Ed. 2015, 54, 3872. (b) Meggers, E. Chem. Commun.
2015, 51, 3290.
(7) (a) Zou, Y.-Q.; Duan, S.-W.; Meng, X.-G.; Hu, X.-Q.; Gao, S.; Chen,
J.-R.; Xiao, W.-J. Tetrahedron 2012, 68, 6914. (b) Lu, Z.; Yoon, T. P.
Angew. Chem. Int. Ed. 2012, 51, 10329. (c) Kumarasamy, E.;
Raghunathan, R.; Jockusch, S.; Ugrinov, A.; Sivaguru, J. J. Am.
Chem. Soc. 2014, 136, 8729. (d) Hurtley, A. E.; Lu, Z.; Yoon, T. P.
Angew. Chem. Int. Ed. 2014, 53, 8991. (e) Liu, Q.; Zhu, F.-P.; Jin,
X.-L.; Wang, X.-J.; Chen, H.; Wu, L.-Z. Chem. Eur. J. 2015, 21,
10326. (f) Mojr, V.; Svobodová, E.; Straková, K.; Neveselý, T.;
Chudoba, J.; Dvořáková, H.; Cibulka, R. Chem. Commun. 2015, 51,
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(18) (a) Cowley, D. J. J. Chem. Soc., Perkin Trans. 2 1975, 1576.
(b) Zhang, S.-Q.; Wang, H.-G.; Pei, K.-M.; Zheng, X. J. Chem. Phys.
2007, 126, 194505.
(19) For further references to the photochemistry of nitroolefins,
see: (a) Ried, W.; Wilk, M. Justus Liebigs Ann. Chem. 1954, 590,
111. (b) Zimmerman, H. E.; Roberts, L. C.; Arnold, R. J. Org. Chem.
1977, 42, 621. (c) Humphry-Baker, R. A.; Salisbury, K.; Wood, G.
P. J. Chem. Soc., Perkin Trans. 2 1978, 659. (d) Grant, R. D.;
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(20) For the emission spectra of the lamps, see for λ = 300 nm, 366
nm: (a) Maturi, M. M.; Wenninger, M.; Alonso, R.; Bauer, A.;
Pöthig, A.; Riedle, E.; Bach, T. Chem. Eur. J. 2013, 19, 7461. λ =
350 nm: (b) Rimböck, K.-H.; Pöthig, A.; Bach, T. Synthesis 2015,
47, 2869. λ = 419 nm: (c) Alonso, R.; Bach, T. Angew. Chem. Int.
Ed. 2014, 53, 4368. λ = 457 nm, 470 nm: (d) Lenhart, D.; Bauer,
A.; Pöthig, A.; Bach, T. Chem. Eur. J. 2016, 22, 6519.
(21) Representative Procedure
29.8 mg of nitrostyrene 1 (199 μmol, 1.00 equiv) and 10.0 equiv
of olefin 2e (168 mg, 2.00 mmol) were dissolved in degassed,
dry CH2Cl2 (c = 20 mM). The reaction solution was irradiated at
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

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L.-M. Mohr, T. Bach
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Synlett
λ = 419 nm in a Duran tube at r.t., and the reaction progress was
monitored by TLC. When no further conversion was observed
by TLC (t = 12 h), the reaction was stopped and all volatiles were
removed. Purification by column chromatography (pen-
tane/Et2O = 20:1) gave product 3e as a yellow oil (27.5 mg, 118
μmol, 59%). When performed on a mmol scale (150 mg 1),
product 3e was obtained in 56% yield (132 mg). 1H NMR (500
MHz, CDCl3, 300 K): δ = 0.71 (s, 3 H, CH3-2), 1.15 (s, 3 H, CH3-3),
1.19 (s, 3 H, CH3-2), 1.24 (s, 3 H, CH3-3), 3.97 (d, 3J = 10.1 Hz, 1 H,
H-1), 4.91 (d, 3J = 10.1 Hz, 1 H, H-4), 7.08–7.13 (m, 2 H, ortho-
HAr), 7.23–7.28 (m, 1 H, para-HAr), 7.30–7.37 (m, 2 H, meta-HAr)
ppm. 13C NMR (101 MHz, CDCl3, 300 K): δ = 19.5 (q, CH3-3), 21.5
(q, CH3-2), 22.8 (q, CH3-3), 24.3 (q, CH3-2), 39.3 (s, C-2), 44.9 (s,
C-3), 49.4 (d, C-1), 84.9 (d, C-4), 127.0 (ortho-CArH). 127.1 (d,
para-CArH), 128.6 (d, meta-CArH), 136.4 (s, CAr) ppm.
Duschmalé, J.; Wennemers, H.; Mukaiyama, T.; Benohoud, M.;
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(27) The reaction time was 6 h. If the isomerization was performed
starting from cis-β-nitrostyrene under otherwise identical con-
ditions, the cis/trans ratio was 82:18.
(22) For thermal [2+2] cycloaddition reactions of trans-β-nitrosty-
rene (1) and olefins, see: (a) Brannock, K. C.; Bell, A.; Burpitt, R.
D.; Kelly, C. A. J. Org. Chem. 1964, 29, 801. (b) Scheeren, H. W.;
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chemistry, 2nd ed.; Marcel Dekker: New York, 1993, 80.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E