Photo-induced atom-transfer radical reactions using charge-transfer complex between iodine and tertiary amine

Article abstract of DOI:10.1248/cpb.c16-00814

In the presence of charge-transfer complexes between iodine and tertiary amines, the aqueous-medium atom-transfer radical reactions proceeded under visible light irradiation without the typical photocatalysts.

Full text of DOI:10.1248/cpb.c16-00814

Vol. 65, No. 1
Chem. Pharm. Bull. 65, 33–35 (2017)
33
Communication to the Editor
1 and i-C3F7I (5eq) in H2O was stirred for 1h with white LED
light (400–700nm, 1000lm) irradiation under Ar atmosphere
(entry 1). In this reaction, 1.1eq of trimethylamine were em-
ployed, because 1.0eq of amine also acts as an electron-donor
leading to C. As expected, the desired product 2 was obtained
in 89% yield. In marked contrast, the reaction did not occur
when MeCN was employed as solvent (entry 2). The use of
(i-Pr)2NEt as a tertiary amine led to enhancement in chemical
yield (entry 3), although pyridine did not promote the reaction
probably due to its low reactivity as an electron-donor (entry
4). The chemical yield of 2 dramatically decreased by using
secondary amine such as (i-Pr)2NH, owing to the oxidation of
secondary amine by I2 (entry 5).25–27) Interestingly, in the ab-
sence of iodine, this transformation took place slowly by using
(i-Pr)2NEt (entry 6). Even in the absence of I2, CT complex
between (i-Pr)2NEt and I2 would be formed, because i-C3F7I
is gradually decomposed to give I2. However, in the absence
Photo-Induced Atom-Transfer Radical
Reactions Using Charge–Transfer
Complex between Iodine and Tertiary
Amine
Eito Yoshioka, Shigeru Kohtani, Takurou Hashimoto,
Tomoko Takebe, and Hideto Miyabe*
School of Pharmacy, Hyogo University of Health Sciences; 1–3–6
Minatojima, Chuo-ku, Kobe 650–8530, Japan.
Received October 17, 2016; accepted October 24, 2016
In the presence of charge–transfer complexes between io-
dine and tertiary amines, the aqueous-medium atom-transfer
radical reactions proceeded under visible light irradiation
without the typical photocatalysts.
Key words radical; iodine; photochemistry; perfluoroalkyl; of amine, the reaction using only iodine did not occur and
charge–transfer complex; aqueous media
the solubility of iodine also decreased without the association
with amine (entry 7). Therefore, this CT complex-promoted
The charge–transfer complex (CT complex) is formed by reaction is differentiated from the reported iodine-mediated
weak association of electron-donor and electron-acceptor. radical reactions.28,29) Theoretical and computational studies
Particularly, the CT complexes between metal atoms and li-
gands are widely studied in inorganic chemistry.1,2) In recent
years, the metal-to-ligand charge transfer in transition metal
Table 1. Iodine-Atom Transfer Reaction Using Charge–Transfer Com-
plexesa)
photocatalysts has been applied to the synthetic organic chem-
istry.3–5) Although the physical properties of organic CT com-
plexes are investigated,6–10) less is known about the utility of
organic CT complexes in synthetic reactions.11–15) In our stud-
ies on the radical reactions using Ru-catalyst or rhodamine
B as a photocatalyst,16–19) we found that the some reactions
proceeded in the absence of these photocatalysts. Therefore,
our laboratory is interested in developing a new method which
doesn’t require the external photocatalysts. In this commu-
nication, we report the experiments to prove the utility of
organic CT complexes between iodine (I2) and tertiary amines
in the aqueous-medium carbon–carbon bond-forming radical
Entry
Amine
Solvent
Yield (%)b)
reactions.
Iodine is known to interact with amines to form the CT
1
Me3N
Me3N
H2O
MeCN
H2O
89
NDd)
98
complexes, which have the two broader absorption bands at
ca. 230–280 and 410–430nm20,21) (Chart 1). Therefore, we
expected that the visible light irradiation of CT complex A in
the ground state gives the excited state B, which may promote
the single electron transfer (SET) from the donor amine to the
acceptor iodine giving the iodine radical.22–24)
2
3
(i-Pr)2NEt
Pyridine
(i-Pr)2NH
(i-Pr)2NEt
None
4
H2O
NDd)
5
6c)
H2O
3
H2O
56
NDd)
7
H2O
At first, we studied the effect of CT complexes derived
from I2 and several amines on the iodine atom-transfer radical
reaction of alkene 1 with i-C3F7I (Table 1). In the presence of
I2 (0.1eq) and trimethylamine (1.1eq), the biphasic solution of
a) Reactions of 1 (1eq) with i-C3F7I (5eq) were carried out in the presence of
I2 (0.1eq) and amine (1.1eq) under the LED light irradiation. The calculation stud-
ies were performed on density functional B3LYP 6–311+G** by using Spartan'10
(WAVEFUNCTION, INC.). b) Isolated yields. c) Reaction was carried out in the
absence of I2 for 4h. d) The formation of product 2 was not detected.
Chart 1. Charge–Transfer Complex between Amine and Iodine
*To whom correspondence should be addressed. e-mail: miyabe@huhs.ac.jp
© 2017 The Pharmaceutical Society of Japan

34
Chem. Pharm. Bull.
Vol. 65, No. 1 (2017)
Table 2. Reaction of 3–8 with i-C3F7Ia)
a) Reactions of 3–8 (1eq) with i-C3F7I (5eq) were carried out in H2O in the pres-
ence of I2 (0.1eq) and (i-Pr)2NEt (1.1eq) for 1h under the LED light irradiation. b)
Isolated yields. c) The formation of product was not detected.
Chart 3. Cascade Radical Addition-Cyclization-Trapping Reaction
Chart 4. Possible Reaction Pathway
precursors (Chart 2). The reaction of 1 with n-C3F7I proceeded
to give the product 14 in 81% yield. Although the reaction
in MeCN did not occur (entry 2 in Table 1), ICH2CN having
cyano group worked as a radical precursor to give the adduct
15 in 43% yield. Moreover, the bromine atom-transfer radical
reaction using CCl3Br took place with moderate chemical ef-
ficiency.
Chart 2. Reaction with Other Carbon Radical Precursors
on halogen bonding interactions have been a subject of current
We finally investigated the radical addition-cyclization-
interest.30,31) To understand the above results, we calculated trapping reaction of symmetrical substrates 17, 19 and 21 in
the optimized structures of iodine complexes. The calculation aqueous media (Chart 3). When i-C3F7I was employed, the
shows that the noncovalent interaction between trimethyl- reaction of 17 was completed within 1h to give the products
amine and I2 is strong to form the stable CT complex, while cis-18a and trans-18a in 81% combined yield. Other radical
pyridine weakly interacts with I2. Additionally, we presume precursors n-C3F7I and c-C6F11I worked well. Similarly, the
that the negligible interaction of MeCN solvent with I2 may reaction of 19 with i-C3F7I gave the products cis-20 and trans-
suppress the formation of CT complex.
20 in 82% combined yield. The reaction of 21 also proceeded
We next explored the iodine atom-transfer radical reac- effectively to give the product 22 in 98% yield with excellent
tion of various alkenes 3–8 with i-C3F7I under the optimized cis-diastereoselectivity.
reaction conditions (Table 2). Except for styrene 8, alkenes
The possible reaction pathway for the generation of i-C3F7
3–7 reacted with excellent chemical efficiencies and regiose- radical is shown in Chart 4. The reaction is initiated by the
lectivities. It is important to note that the reactions of alkene visible light irradiation of CT complex A in the ground state
6 having bromine atom and alkene 7 having hydroxy group to produce the excited state B. We presume the generation
proceeded without any problems.
of an iodine radical via the single electron transfer from the
To study the viability of the present method, n-C3F7I, donor amine to the acceptor iodine in the excited state B,
ICH2CN and CCl3Br were next employed as carbon radical which is evident from observation of the transient species

Vol. 65, No. 1 (2017)
Chem. Pharm. Bull.
10) Rosokha S. V., Kochi J. K., Acc. Chem. Soc., 41, 641–653 (2008).
35
generated in the photoexcitation of quinuclidine–I2 and trieth-
ylenediamine–I2 complexes by means of transient absorption
spectroscopy,22) although it cannot be excluded that the excited
state B acts as a reducing agent toward i-C3F7I. Finally, an
iodine radical reacts with i-C3F7I to give i-C3F7 radical and the
regenerated iodine.
11) Koshima H., Ding K., Chisaka Y., Matsuura T., Ohashi Y., Mukasa
M., J. Org. Chem., 61, 2352–2357 (1996).
12) González-Béjar M., Stiriba S.-E., Miranda M. A., Pérez-Prieto J.,
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In summary, we have demonstrated that CT complexes be-
tween iodine and tertiary amines have the potential to induce
the atom-transfer radical reactions in aqueous media. In addi-
tion to typical photocatalysts, the CT complexes disclosed a
broader utility of photo-induced radical reactions.
14) Kandukuri S. R., Bahamonde A., Chatterjee I., Jurberg I. D.,
Escudero-Adán E. C., Melchiorre P., Angew. Chem. Int. Ed., 54,
1485–1489 (2015).
15) Woźniak Ł., Murphy J. J., Melchiorre P., J. Am. Chem. Soc., 137,
5678–5681 (2015).
16) Yoshioka E., Kohtani S., Tanaka E., Miyabe H., Synlett, 24, 1578–
1582 (2013).
17) Yoshioka E., Kohtani S., Tanaka E., Hata Y., Miyabe H., Tetrahe-
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18) Yoshioka E., Kohtani S., Jichu T., Fukazawa T., Nagai T., Takemoto
Y., Miyabe H., Synlett, 26, 265–270 (2015).
19) Yoshioka E., Kohtani S., Jichu T., Fukazawa T., Nagai T., Ka-
washima A., Takemoto Y., Miyabe H., J. Org. Chem., 81, 7217–7229
(2016).
Acknowledgment This work was supported by JSPS
KAKENHI Grant-in-Aid for Scientific Research (C) Grant
Number 16K08188 (to H.M.).
Conflict of Interest The authors declare no conflict of
interest.
20) Nagakura S., J. Am. Chem. Soc., 80, 520–524 (1958).
21) Yada H., Tanaka J., Nagakura S., Bull. Chem. Soc. Jpn., 33, 1660–
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