Electron transfer to benzenes by photoactivated neutral organic electron donor molecules

Article abstract of DOI:10.1002/anie.201200084

Powerful reduction reactions: Simple organic electron donors, composed solely of the elements carbon, hydrogen, and nitrogen, reduce ground-state benzene rings to their radical anions by electron transfer upon photoactivation (DMF=dimethylformamide).

Full text of DOI:10.1002/anie.201200084

Angewandte
Chemie
DOI: 10.1002/anie.201200084
Reduction of Benzenes
Electron Transfer to Benzenes by Photoactivated Neutral Organic
Electron Donor Molecules**
Elise Cahard, Franziska Schoenebeck,* Jean Garnier, Sylvain P. Y. Cutulic, Shengze Zhou, and
John A. Murphy*
Benzene (E0 = À3.42 V vs. a saturated calomel electrode,
SCE[1]) and its close analogs are among the most challenging
organic substrates for reduction. Very few chemical entities
have the power to add an electron to ground-state benzene,
and these are all derived from highly reactive metals. Thus,
the alkali metals sodium (E0 = À2.71 V) and lithium (E0 =
À3.04 V) dissolve in liquid ammonia to form solvated
electrons together with the corresponding metal cations,[2]
and similarly calcium (E0 = À2.89 V) and lithium dissolve in
aliphatic amines.[3] These solvated electrons can convert
benzene to its radical anion. In the Birch reduction, a proto-
nation step follows for the arene radical anion, but this step is
independent of the electron-rich metal. Very recently, a com-
plex derived from samarium(II) iodide, also in the presence of
an amine, joined this exclusive set of reagents, in the
reduction of the substrate, 4-methoxybenzyl alcohol.[4,5] We
now explore whether a completely organic molecule can
convert close analogs of benzene to their radical anions,
mirroring the behavior of the metals described above. The
choice of arene substrate determines the level of the
challenge. E0 values are not routinely available for ben-
zenes,[1] other than those activated by electron-withdrawing
groups. However, comparison of the computed lowest unoc-
cupied molecular orbital (LUMO) energies of a range of
arenes shows[6] (see Table S1 in the Supporting Information)
that benzenes substituted by saturated carbon groups have
LUMO energies that lie within 0.2 eV of the value for
benzene itself. In contrast, both extended arenes and arenes
substituted by electron-withdrawing groups (e.g. CN, CO2Me)
have much lower LUMO energies and are much easier to
reduce. Accordingly, in choosing a discriminating test for
a reducing agent, the latter substrates are not appropriate. We
have chosen 1,2-diphenylcyclopropanes 4 and 5 and their
derivatives 6–11 as the substrates for our study. Both 4 and 5
have LUMO energies within 0.2 eV of that of benzene, are
relatively involatile, and can report the intermediacy of
radical anions through the opening of the cyclopropane ring
(see Scheme 1).
Our recent research has probed the ground-state donor
properties of highly reactive neutral organic reducing agents.
Thus, we have shown that the neutral ground-state organic
electron donor 1[7,8] (Scheme 1) reduces iodoarenes[9,10] to aryl
radicals[11] while the stronger donors 2[12] and 3[13] under
milder conditions, afford aryl anions from the same substrates
[*] E. Cahard, J. Garnier, S. P. Y. Cutulic, Dr. S. Zhou,
Prof. Dr. J. A. Murphy
Department of Pure and Applied Chemistry
University of Strathclyde
295 Cathedral Street, Glasgow G1 1XL (UK)
E-mail: john.murphy@strath.ac.uk
Prof. Dr. F. Schoenebeck
ETH Zꢀrich Laboratory for Organic Chemistry
Wolfgang Pauli Straße 10, 8093 Zꢀrich (Switzerland)
E-mail: schoenebeck@org.chem.ethz.ch
[**] We thank the EPSRC and the ETH for funding and the EPSRC
National Mass Spectrometry Service, Swansea, for spectra, and we
thank Markus Reiher (ETH) for helpful discussions.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201200084.
Scheme 1. Reactions of organic electron donors with substrates.
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through transfer of two electrons. These donors also reduce
sulfonamides, acyloin derivatives, and Weinreb amides.[13]
Nevertheless, our efforts to reduce more challenging
arenes, for example, chlorobenzenes, had been unsuccessful,
and so this was the starting point for studies with the
photoactivated donor 3.
ical purity of the re-formed cyclopropane should be dimin-
ished. Alternatively, the open radical anion ra 4 could
1) receive another electron to become
a dianion, or
2) abstract a proton or a hydrogen atom, on its way to the
diarylpropane 16. The cis-isomers of 1,2-diarylcyclopropanes
4, 6, and 8 and their respective trans-isomers 5, 7 and 9, were
prepared from known stilbenes. Irradiation of each separate
isomer with donor 3 (Table 1, entries 1–4) was undertaken in
inert atmosphere and, for each irradiation, a blank experi-
ment (in which no donor 3 was present) was conducted
simultaneously by placing two otherwise identical vessels in
the irradiation chamber at the same time. The products were
monitored by 1H NMR spectroscopy, which was used for both
quantitation and identification of the products. The product
identities were confirmed by GCMS in these experiments.
With the 1,2-diphenylcyclopropane study, the cis starting
material represented as 4 contained a 2:98 ratio of the
trans:cis isomers 5:4. The blank experiment performed in the
absence of donor 3 afforded an unchanged 2:98 ratio of these
isomers, while the product of irradiation in the presence of
donor 3 afforded a 19:81 ratio (79% recovery) as shown in
Table 1 (entry 1) together with the entries for the other
substrates 5, 6, and 7. All the isomers show stereomutation,
with the effects being more pronounced for the cis-substrates,
as expected.
The experiment was also carried out for both of the
chlorophenyl substrates 8 and 9. These cases showed dech-
lorination as a competitive reaction, providing further evi-
dence of the involvement of radical anions of the substrates
(see the Supporting Information).
We applied computational studies to get deeper
insights.[18] The intermediates and transition states were
optimized with UB3LYP/6-31 + G(d)[19] or CBS-QB3 and
energies were subsequently calculated at UCCSD(T)/6-
31G(d)//UB3LYP/6-31 + G(d).[20] The calculated reaction
profiles for the diphenylcyclopropanes 4 and 5 are shown
above (Figure 1). Using UB3LYP/6-31 + G(d), we calculate
a very small barrier for the ring opening of the cis radical
anion. At CBS-QB3, the ring opening is even spontaneous
upon optimization of ra 4 (the radical anion of 4). Further
assessment of the ring opening with UCCSD(T)/6-31G(d)
Donor 3 is deep purple in color with absorption maxima at
260, 345, and 520 nm and so is susceptible to near-UV
excitation. A carousel arrangement of 12 ꢀ 8 W F8T5-BLB
lamps with emission at 365 nm was selected for the initial set
of experiments with 3. The emission spectrum of these lamps
shows good overlap with the absorption of donor 3 centered
at 345 nm (see the Supporting Information). To set a bench-
mark for the photoactivation process, substrate 12 was
selected for reaction with donor 3. Previous experiments
had shown that in the presence of 3 (3 equiv) at 1008C, but
with no irradiation, no reduced product 13 was produced;
instead, 95% of the starting material 12 was recovered. In the
current work, irradiation at room temperature in the presence
of donor 3 now led to the reduced product 13 in 87% yield
(see Scheme 1). Blank reactions determined that the chlo-
ride 12 did not react under these irradiation conditions, in the
absence of donor 3. This successful reductive dechlorination
encouraged us to explore whether the photoexcited donor 3
might be capable of transferring an electron to the more
challenging non-halogenated benzenes.
Phenylcyclopropylcarbinyl radicals, for example, 14 have
previously been used as probes for very fast radical reactions
by the teams of Newcomb[14a] and Ingold[14b] through diag-
nostic ring-opening to phenylbutenyl radicals 15. Our plan
was to take a single isomer of 1,2-diphenylcyclopropane, for
example, 4 and to use the excited donor 3 to transfer an
electron to it to afford the radical anion, ra 4, and then to
monitor the outcome of the experiment for formation of the
ring-opened product 16 or for partial equilibration of the
stereochemistry of the initial isomer.[15–17] The ring-opening of
closed ra 4 to open ra 4 should be fast, but the fate of open
ra 4 was not certain. Since back electron transfer is common
in photochemical processes, the cyclopropane could form
again from open ra 4. However, since the 3-carbon chain in
open ra 4 should be conformationally fluid, the stereochem-
Table 1: Outcome of the irradiation of arene substrates in the presence of donors 2 or 3. For entries 1–4, the products were isolated and the isomer
ratios determined by 1H NMR spectroscopy. For entries 8-12, 1H NMR calibration against an added internal anisole standard was performed
(CPs=cyclopropanes, DPs=diarlypropanes).
Entry
Arene
CPs starting
trans/cis ratio
Electron donor
(equiv)
Irradiation time [h]
(energy [W])
Isolated trans/cis
ratio of CPs
Isolated
yield [%]
CPs trans/cis
yield [%]
DPs (yield [%])
1
2
3
4
5
6
7
8
9
4
6
5
7
4
6
5
7
4
6
5
7
2:98
2:98
99.5:0.5
99:1
2:98
2:98
99.5:0.5
99:1
2:98
2:98
99.5:0.5
99:1
3 (3)
3 (1.5)
3 (3)
3 (1.5)
3 (2)
3 (2)
3 (2)
3 (2)
2 (2)
2 (2)
2 (2)
2 (2)
24 (8ꢁ12)
24 (8ꢁ12)
24 (8ꢁ12)
17 (8ꢁ12)
90 (2ꢁ100)
90 (2ꢁ100)
90 (2ꢁ100)
90 (2ꢁ100)
90 (2ꢁ100)
90 (2ꢁ100)
90 (2ꢁ100)
90 (2ꢁ100)
19:81
14:86
95:5
95:5
n.a.
n.a.
n.a.
n.a.
n.a.
79
59
88
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
16 (6.1)
17 (2.8)
16 (13.7)
17 (5.6)
16 (35.1)
17 (21.2)
16 (34.8)
17 (23.9)
35
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
46.8; 19.6
28.3; 31.3
54.2; 7.0
41.8; 5.3
17.7; 17.7
6.5; 54.5
32.7; 3.3
35.3; 1.8
10
11
12
n.a.
n.a.
n.a.
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Figure 1. Reaction path energy profile for 1,2-diphenylcyclopropane. The electronic energies are shown (in kcalmolÀ1) and the enthalpies are given
in parentheses (at UB3LYP/6-31+G(d) level of theory). For additional levels of theory, see the text.
energies confirms that there is essentially no barrier for the
ring opening (DDE° = À0.1 kcalmolÀ1). The cleavage is
exothermic by 11 kcalmolÀ1 at DFT and CCSD(T) levels of
theory, disfavoring therefore the reverse ring-closing process.
The rotational barrier from the ring-opened cis radical anion
open ra 4 to the corresponding trans isomer open ra 5 (and
vice versa) is low and feasible (see Figure 1). Ring closure of
the trans radical anion, open ra 5, is calculated to have
a barrier of 9.8 kcalmolÀ1 at B3LYP and 8.2 kcalmolÀ1 at
CCSD(T), but the ring-closed trans radical anion closed ra 5
(obtained following the intrinsic reaction coordinate) is in fact
of essentially the same energy as the transition state (TS)
itself.[21]
This suggests that ring closure of the radical anions is
disfavored. The ring-opened radical anion intermediates (cis
or trans) could readily undergo back electron transfer to the
corresponding singlet biradical in the reaction. Optimization
of the singlet biradical intermediate indeed showed sponta-
neous ring closure upon optimization (see the Supporting
Information). The alternative triplet biradical is energetically
disfavored (it is DHrxn = 15.3 kcalmolÀ1 higher in energy than
diphenylcyclopropane 4).
(16 and 17, respectively), the expected products of reductive
trapping of the radical anion.[22]
Our previous studies had shown that donors 2 and 3 have
similar oxidation potentials in their ground state, and so we
also explored the reactions of donor 2 (see Table 1, entries 9–
12). The qualitative results are the same, although donor 2 is
more effective in promoting the formation of the 1,3-
diphenylpropanes, with about 35% being formed from each
isomer of 1,2-diphenylcyclopropane.
In summary, we showed that in the presence of the simple
photoexcited super electron donors 2 and 3, ring opening of
the diphenylcyclopropanes results. This is the first time that
a neutral organic reducing agent, upon photoexcitation, has
achieved such a challenging reduction reaction, and yet the
active electron donors are simple structures derived from
pyridine and imidazole rings composed exclusively of carbon,
hydrogen, and nitrogen elements. Pyridines and imidazoles
occur widely in the pool of chemicals that are biosynthesized
naturally and so it is noteworthy that nature could evolve very
powerful reductive reactions even in environments that are
depleted in redox-active metals.
Received: January 4, 2012
Published online: March 2, 2012
Thus, the data suggest that initial ring opening can take
place through reduction. Subsequent isomerization (i.e.
rotation) takes place through the radical anion intermediates
and upon oxidation of the ring-opened cis or trans radical
anion, very fast ring closure of the singlet biradical takes
place. A triplet biradical, if formed, might give rise to rotation
and isomerization also, but would be in competition with
decay to the singlet biradical and subsequent spontaneous
ring closure.
Keywords: electrochemistry · electron donors ·
.
electron transfer · radicals · reduction
[1] J. Mortensen, J. Heinze, Angew. Chem. 1984, 96, 64 – 65; Angew.
Chem. Int. Ed. Engl. 1984, 23, 84 – 85.
Returning to laboratory experiments, in efforts at increas-
ing the amount of stereomutation, the photoactivated reac-
tions were then repeated for substrates 4, 5, 6, and 7, but with
more intense irradiation (UVP Black-Ray lamps, 2 ꢀ 100 W,
365 nm focused irradiation) and for an extended reaction time
of 90 h using two equivalents of the donor. This afforded
higher percentages of isomerization (Table 1, entries 5–8) and
identification of minor components as the 1,3-diarylpropanes
[2] A. J. Birch, Q. Rev. Chem. Soc. 1950, 4, 69 – 93.
[3] R. A. Benkeser, F. G. Belmonte, J. Kang, J. Org. Chem. 1983, 48,
2796 – 2802.
[4] T. Ankner, G. Hilmersson, Tetrahedron 2009, 65, 10856 – 10862.
[5] Whereas the addition of an electron to benzene in its ground
state is an extremely challenging reaction, there are many
reports of aliphatic amines or other electron-rich species acting
as electron donors to an excited state of benzene (irradiation at
254 nm). Promotion of an electron from the benzene HOMO to
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.
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the LUMO occurs, and the amine transfers an electron to fill the
hole thereby created. See: a) D. Bryce-Smith, M. T. Clarke, A.
Gilbert, G. Klunklin, C. Manning, J. Chem. Soc. Chem.
Commun. 1971, 916 – 917; b) J. A. Barltrop, Pure Appl. Chem.
1973, 33, 179 – 195; M. Kropp, G. B. Schuster, Tetrahedron Lett.
1987, 28, 5295 – 5298; c) Y. Yoshimi, A. Ishise, H. Oda, Y.
Moriguchi, H. Kanezaki, Y. Nakaya, K. Katsuno, T. Itou, S.
Inagaki, T. Morita, M. Hatanaka, Tetrahedron Lett. 2008, 49,
3400 – 3404.
[14] a) S.-Y. Choi, P. H. Toy, M. Newcomb, J. Org. Chem. 1998, 63,
8609 – 8613; b) R. Hollis, L. Hughes, V. W. Bowry, K. U. Ingold,
J. Org. Chem. 1992, 57, 4284 – 4287.
[15] The radical cation of 1,2-diphenylcyclopropane has been widely
studied and is known to undergo facile ring opening; starting
from either the cis or the trans isomer, stereomutation of 1,2-
diphenylcyclopropane has been shown in the presence of
appropriate electron acceptors using photoelectron transfer.[16]
However, to our knowledge, the radical anion has not previously
been probed.
[16] a) Isomerization upon irradiation at 254 nm: E. W. Valyocsik, P.
Sigal, J. Org. Chem. 1971, 36, 66 – 72; b) Isomerisation upon
irradiation of an electron-poor sensitizer. Y. Inoue, H. Shi-
moyama, N. Yamasaki, A. Tai, Chem. Lett. 1991, 593 – 596.
[17] a) Y. Inoue, N. Yamasaki, H. Shimoyama, A. Tai, J. Org. Chem.
1993, 58, 1785 – 1793; b) G. S. Hammond, R. S. Cole, J. Am.
Chem. Soc. 1965, 87, 3256 – 3257; c) K. Mizuno, N. Ichinose, Y.
Otsuji, Chem. Lett. 1985, 455 – 458.
[6] Calculated at B3LYP/6-31 + G(d) level and for I also involving
an ECP (LANL2DZ). A. P. Davis, A. J. Fry, J. Phys. Chem. A
2010, 114, 12299 – 12304. Gaussian09, RevisionA.01, M. J. Frisch
et al. (see the Supporting Information for the full reference).
[7] J. R. Ames, M. A. Houghtaling, D. L. Terrian, T. P. Mitchell,
Can. J. Chem. 1997, 75, 28 – 36. À0.82 V vs. SCE = À0. 58 V vs.
SHE = À0.78 V vs. Ag/AgCl (saturated KCl).
[8] S. Hꢁnig, D. Scheutzov, H. Schlaf, Justus Liebigs Ann. Chem.
1972, 765, 126 – 132.
[9] L. Pause, M. Robert, J.-M. Savꢂant, J. Am. Chem. Soc. 1999, 121,
7158 – 7159.
[18] Gaussian09, RevisionA.01, M. J. Frisch et al. (see the Support-
ing Information for the full reference).
[10] C. P. Andrieux, J. Pinson, J. Am. Chem. Soc. 2003, 125, 14801 –
14806.
[11] J. A. Murphy, T. A. Khan, S.-Z. Zhou, D. W. Thomson, M.
Mohan, Angew. Chem. 2005, 117, 1380 – 1384; Angew. Chem. Int.
Ed. 2005, 44, 1356 – 1360.
[19] This level of theory was shown to be reliable for the cyclopropyl
radical cations: a) T. Bally, Z. Zhu, J. Wirz, M. Fꢁlscher, J.-Y.
Hasegawa, J. Chem. Soc. Perkin Trans. 2 2000, 2311 – 2318;
b) R. A. Moss, R. R. Sauers, F. Zheng, X. Fu, T. Bally, A.
Maltsev, J. Am. Chem. Soc. 2004, 126, 8466 – 8476; c) J. Oxgaard,
O. Wiest, Eur. J. Org. Chem. 2003, 1454 – 1462; For an
application of B3LYP for radical anions, see: K. Piech, T.
Bally, A. Sikora, A. Marcinek, J. Am. Chem. Soc. 2007, 129,
3211 – 3217. For a discussion of the failure of DFT in the
treatment of radical cations, see: B. Braꢃda, P. C. Hiberty, A.
Savin, J. Phys. Chem. A 1998, 102, 7872 – 7877.
[12] a) R. P. Thummel, V. Goulle, B. Chen, J. Org. Chem. 1989, 54,
3057 – 3061; b) T. A. Taton, P. Chen, Angew. Chem. 1996, 108,
1098 – 1100; Angew. Chem. Int. Ed. Engl. 1996, 35, 1011 – 1013.
[13] a) J. A. Murphy, S.-Z. Zhou, D. W. Thomson, F. Schoenebeck, M.
Mohan, S. R. Park, T. Tuttle, L. E. A. Berlouis, Angew. Chem.
2007, 119, 5270 – 5275; Angew. Chem. Int. Ed. 2007, 46, 5178 –
5183; b) J. A. Murphy, J. Garnier, S. R. Park, F. Schoenebeck, S.-
Z. Zhou, A. T. Turner, Org. Lett. 2008, 10, 1227 – 1230; c) J. A.
Murphy, J. Garnier, S.-Z. Zhou, A. T. Turner, Synlett 2008, 2127 –
2131; d) F. Schoenebeck, J. A. Murphy, S.-Z. Zhou, Y.
Uenoyama, Y. Miclo, T. Tuttle, J. Am. Chem. Soc. 2007, 129,
13368 – 13369; e) S. P. Y. Cutulic, J. A. Murphy, H. Farwaha, S.-
Z. Zhou, E. Chrystal, Synlett 2008, 2132 – 2136.
[20] For a discussion of methods for the calculation of three-centered
radical anions, including CCSD(T), see: B. Braꢃda, L. Thogersen,
W. Wu, P. C. Hiberty, J. Am. Chem. Soc. 2002, 124, 11781.
[21] At UCCSD(T) level the energy difference is À0.05 kcalmolÀ1
[22] M. Vondenhof, J. Mattay, Chem. Ber. 1990, 123, 2457 – 2459.
.
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