Photochemical formal alkadiene insertion into an aromatic C-CN bond using cyanide ion as a catalyst

Article abstract of DOI:10.1246/cl.2010.462

A reaction involving formal alkadiene insertion into a C-CN bond taking place via a catalytic photo-NOCAS mechanism was developed. The process involves photoirradiation of an acetonitrile solution containing 2,5-dimethyl-2,4- hexadiene (1), pdicyanobenzene (p-DCB), phenanthrene (Phen), and a catalytic amount (20mol%) of tetra-n-butylammonium cyanide. The reaction proceeds in the absence of noble metals and under mild conditions (ambient temperature without bases). This is the first example of a photo-NOCAS reaction in which a catalytic amount of nucleophilic species is employed to promote the process.

Full text of DOI:10.1246/cl.2010.462

doi:10.1246/cl.2010.462
462
Published on the web March 31, 2010
Photochemical Formal Alkadiene Insertion into an Aromatic C-CN Bond
Using Cyanide Ion as a Catalyst
³
Maki Ohashi, Hajime Maeda, and Kazuhiko Mizuno*
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University,
1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531
(Received February 3, 2010; CL-100109; E-mail: mizuno@chem.osakafu-u.ac.jp)
Table 1. Photochemical C-CN insertion reactiona
A reaction involving formal alkadiene insertion into a C-CN
CN
CN
bond taking place via a catalytic photo-NOCAS mechanism was
developed. The process involves photoirradiation of an aceto-
nitrile solution containing 2,5-dimethyl-2,4-hexadiene (1), p-
dicyanobenzene (p-DCB), phenanthrene (Phen), and a catalytic
amount (20 mol %) of tetra-n-butylammonium cyanide. The
reaction proceeds in the absence of noble metals and under mild
conditions (ambient temperature without bases). This is the first
example of a photo-NOCAS reaction in which a catalytic amount
of nucleophilic species is employed to promote the process.
h
ν
R
+
+
cyanide (20 mol%)
Phen, additive
2
CN
R
p-DCB
1
3 (R = CN)
4 (R = OH)
5 (R = CN)
6 (R = OH)
Yieldsb/%
Entry
1
Cyanide
Additive
Solvent
3
4
5
6
MeCN/
H2O
MeCN
KCN
®
®
19 28
3
8
2c
3
4
KCN
KCN
0
0
0
0
0
0
2
0
0
0
0
3
2
Activation of essentially unreactive chemical bonds such as
aromatic C-CN bonds1 has been actively studied in recent years
but it remains a challenging task.2-4 Reactions for this purpose
often require severe conditions and noble metal catalysts. As a
result, the development of C-CN bond cleavage reactions that
proceed under mild and noble metal-free conditions is an
important goal from the viewpoint of synthetic utility.
Photochemical reactions serve as promising methods to
cleave inert bonds. Several years ago, Arnold and his co-workers
described photo-NOCAS (nucleophile-olefin combination, ar-
omatic substitution) reactions of p-dicyanobenzene (p-DCB,
terephthalonitrile) and 2,5-dimethyl-2,4-hexadiene (1) in a
methanolic solution, which proceed via photochemically in-
duced ipso-substitution of aromatic cyano groups (eq 1).5,6
18-crown-6d MeCN 36
n-Bu4N+CN
®
MS4Ae
MeCN 60
MeCN 56
¹
¹
5
n-Bu4N+CN
aConditions: 300-W high-pressure mercury lamp, Pyrex filter, 1
(75 ¯mol), p-DCB (25 ¯mol), Phen (25 ¯mol), cyanide (5 ¯mol),
in MeCN (4 mL)-H2O (1 mL) or in MeCN (5 mL), under Ar, rt,
1
20 h. bDetermined by H NMR analysis based on the amount of
c
p-DCB (for 3 and 4) and 1 (for 5 and 6) used. Photoreaction
d
e
was carried out in a suspension. 5 ¯mol. 100 mg.
of cyanide ion in the photo-NOCAS reaction mixture would
enable the operation of a chain mechanism for formal alkadiene
insertion into aromatic C-CN bonds.7
CN
h
ν
p-DCB
1
3 (80%)
+
ð2Þ
h
ν
KCN (excess)
18-crown-6 (cat.)
biphenyl
+
biphenyl
MeOH, MeCN
MeCN
CN
CN
CN
p-DCB
1
ð1Þ
In exploratory studies aimed at testing this proposal, an
acetonitrile-water (4:1) solution containing 1, p-DCB, phenan-
threne (Phen),8,9 and a catalytic amount (20 mol %) of potassium
cyanide was photoirradiated for 20 h (Table 1, Entry 1). This
process afforded a complex product mixture that contained the
desired adduct 3 (19%) along with undesired products 4-6 (28,
3, and 8%, respectively).10,11 Recognizing that products 4 and 6
arise by the addition of water (or formally hydroxide ion) to the
cation radical of 1, we assumed that photoreactions in solutions
that did not contain water would increase the selectivity for
production of 3. However, potassium cyanide has a very low
solubility in anhydrous acetonitrile. As a result, photoirradiation
of a suspension of this cyanide salt in anhydrous acetonitrile did
not lead to formation of any recognizable products, and only
degradation of p-DCB was observed (Entry 2).
+
OMe
CN
2 (82%)
3 (2%)
These workers noticed that not only the typical photo-NOCAS
product 2 (82%) is produced in this reaction, but also the
cyanide containing adduct 3 (2%) is formed. Further inves-
tigations demonstrated that when an excess of potassium cyanide
is included in the reaction mixture 3 is generated in a high yield
(80%) (eq 2). This finding suggests that photo-NOCAS reaction
with free cyanide ion as a nucleophile is the true source of 3. It
has been proposed that cyanide ion, involved in the formation
of 3 in methanol (eq 1), comes from ipso-substitution on the
radical anion of p-dicyanobenzene (p-DCB●¹). Based on this
suggestion, we expected that incorporation of a catalytic amount
An optimal procedure for highly selective formation of the
formal insertion product 3 was uncovered. At first, 18-crown-6
(equimolar to potassium cyanide) was employed as an additive
Chem. Lett. 2010, 39, 462-463
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

463
CN
CN
p-DCB
NC
CN
CN
CN
p-DCB
1Phen*
Phen
B
CN
CN
-
h
ν
Phen
CN Cycle
3
A
(Initial Step)
KCN or
n-Bu4N+CN-
CN
1
1
Scheme 1. Plausible mechanism for the formation of 3.
to improve the solubility of potassium cyanide in dry acetonitrile
(Entry 3). Despite the high selectivity observed for the photo-
reaction in the presence of the crown ether, the process might not
be synthetically suitable because of the low yield (36%) of 3
formed and difficulties associated with separation of the crown
ether. Use of an acetonitrile-soluble cyanide source, tetra-n-
butylammonium cyanide, resolved this problem and led to an
optimal method for carrying out the photo-NOCAS reaction.
Thus, photoirradiation of a mixture of 1 and p-DCB in
anhydrous acetonitrile, containing tetra-n-butylammonium cya-
nide, led to formation of 3 in a 60% yield (Entry 4).13 When a
powder form of molecular sieve (MS) 4A was included to
remove trace amounts of water, no significant change in the
product distribution was observed (Entry 5).
AREA) program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT) of Japan.
References and Notes
³
Present address: Division of Material Sciences, Graduate School
of Natural Science and Technology, Kanazawa University,
Kakuma-machi, Kanazawa 920-1192.
1
2
Bond-dissociation energy (¦HBDE) for Ph-CN is 134 kcal mol¹1: C.
Galli, P. Gentili, Acta Chem. Scand. 1998, 52, 67.
For reviews, see: a) M. Tobisu, N. Chatani, Chem. Soc. Rev. 2008, 37,
300. b) S. M. Bonesi, M. Fagnoni, A. Albini, Angew. Chem., Int. Ed.
2008, 47, 10022; S. M. Bonesi, M. Fagnoni, A. Albini, Angew. Chem.
2008, 120, 10172.
3
4
5
a) J. A. Miller, Tetrahedron Lett. 2001, 42, 6991. b) J. A. Miller, J. W.
Dankwardt, Tetrahedron Lett. 2003, 44, 1907. c) J. M. Penney, J. A.
Miller, Tetrahedron Lett. 2004, 45, 4989. d) J. A. Miller, J. W.
Dankwardt, J. M. Penney, Synthesis 2003, 1643.
a) M. Tobisu, Y. Kita, N. Chatani, J. Am. Chem. Soc. 2006, 128, 8152.
b) Y. Nakao, S. Oda, T. Hiyama, J. Am. Chem. Soc. 2004, 126, 13904.
c) M. Zhang, Z.-F. Lu, Y. Liu, G. Grampp, H.-W. Hu, J.-H. Xu,
Tetrahedron 2006, 62, 5663.
a) D. Mangion, D. R. Arnold, Acc. Chem. Res. 2002, 35, 297. b) D.
Mangion, D. R. Arnold, in CRC Handbook of Organic Photo-
chemistry and Photobioligy, 2nd ed., ed. by W. M. Horspool, F. Lenci,
CRC Press, Florida, 2004, Chap. 40. c) K. Mizuno, Y. Otsuji, Top.
Curr. Chem. 1994, 169, 301.
A typical photo-NOCAS mechanistic pathway is respon-
sible for the formation of 3.5,6,10,12 The route is initiated by
single electron transfer (SET) from the singlet excited state of
Phen (1Phen*) to p-DCB (¦Get = ¹0.3 eV), which is then
followed by SET from 1 to Phen●+ (Scheme 1) to give 1●+
(¦Get = ¹0.4 eV).8 Addition of cyanide ion to 1●+ affords the
allylic radical intermediate A●, which couples with p-DCB●¹ to
¹
form B . Regeneration of the aromatic ring affords the three-
6
7
K. A. McManus, D. R. Arnold, Can. J. Chem. 1994, 72, 2291.
Iron complex-catalyzed photochemical C-CN bond cleavage has been
reported: a) H. Nakazawa, K. Kamata, M. Itazaki, Chem. Commun.
2005, 4004. b) H. Nakazawa, M. Itazaki, K. Kamata, K. Ueda, Chem.
Asian J. 2007, 2, 882.
component adduct 3 and regenerates cyanide ion. The formation
of the cyanide containing dimer 5 is a result of dimerization of
A●.11 Alcohols 4 and 6 are formed by similar reaction
mechanisms to those of 3 and 5, respectively, with water or
hydroxide ion serving as the nucleophile.
The process described above corresponds to a formal
alkadiene insertion reaction into an aromatic C-CN bond.
Importantly, it takes place under mild (ambient temperature and
without base) and noble metal-free conditions. It also represents
the first example of the use of a catalytic amount of nucleophilic
species to promote photo-NOCAS reactions. We believe that this
type of catalytic photoreaction can also be applied to the other
photo-NOCAS reactions.5
8
9
Phen acts as a redox photosensitizer: T. Majima, C. Pac, A. Nakasone,
H. Sakurai, J. Am. Chem. Soc. 1981, 103, 4499.
We used Phen instead of biphenyl to lower the photon energy to be
injected into the reaction system, expecting the improvement of
selectivity (excited singlet energy of Phen and biphenyl is 345 and
391 kJ mol¹1, respectively): S. L. Murov, I. Carmichael, L. Hug,
Handbook of Photochemistry, 2nd ed., Marcel Dekker, New York,
1993, Sect. 1.
10 M. Ohashi, K. Nakatani, H. Maeda, K. Mizuno, J. Org. Chem. 2008,
73, 8348.
11 a) K. Mizuno, C. Pac, H. Sakurai, J. Am. Chem. Soc. 1974, 96, 2993.
b) M. Ohashi, H. Maeda, K. Mizuno, Chem. Lett. 2006, 35, 482. c) M.
Ohashi, K. Nakatani, H. Maeda, K. Mizuno, Org. Lett. 2008, 10,
2741.
12 Z.-F. Lu, Y.-M. Shen, J.-J. Yue, H.-W. Hu, J.-H. Xu, J. Org. Chem.
2008, 73, 8010.
13 Supporting Information is available electronically on the CSJ-Journal
Web site, http://www.csj.jp/journals/chem-lett/index.html.
This work was partially supported by Grant-in-Aids for
Scientific Research on Priority Areas (429) (No. 16033252),
Scientific Research (B) (Nos. 15350026 and 20044027), JSPS
Fellows (No. 20-4975), and the Cooperation for Innovative
Technology and Advanced Research in Evolutional Area (CITY
Chem. Lett. 2010, 39, 462-463
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/