Photoinduced oxyamination of enamines and aldehydes with TEMPO catalyzed by [Ru(bpy)3]2+

Article abstract of DOI:10.1246/cl.2009.166

Tris(bipyridyl)rutheriium(II) ([Ru(bpy)3J²⁺: TB(II)) catalyzes oxidative coupling of enamines and aldehydes with 2,2,6,6- tetramethylpiperidinyl-l-oxy (TEMPO) under irradiation of visible light to afford α-oxyaminated carbonyl compounds. The vi

Full text of DOI:10.1246/cl.2009.166

166
Chemistry Letters Vol.38, No.2 (2009)
Photoinduced Oxyamination of Enamines and Aldehydes
with TEMPO Catalyzed by [Ru(bpy)3]2þ
Takashi Koikeꢀ and Munetaka Akitaꢀ
Chemical Resources Laboratory, Tokyo Institute of Technology, R1-27, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503
(Received November 18, 2008; CL-081087; E-mail: makita@res.titech.ac.jp)
Tris(bipyridyl)ruthenium(II) ([Ru(bpy)3]2þ: TB(II)) cata-
O
N
O
O
N
lyzes oxidative coupling of enamines and aldehydes with
2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) under irradia-
tion of visible light to afford ꢀ-oxyaminated carbonyl com-
pounds. The visible light irradiation is essential to generate the
triplet excited state of ꢀTB(II) which acts as an oxidizing agent.
This is a new procedure for radical coupling based on single
electron transfer mediated by photoactivated TB.
H
C6H5
1 equiv TB(II)•(PF6)2
+
O
N
1) CH3CN/CH2Cl2 ([1a]= 0.01 M)
H
rt, 5 h, h
ν > 420 nm (Xe lamp)
1:1
2) H2O
TEMPO
C6H5
1a
3a
84% isolated yield
Scheme 2. Reaction of enamine with TEMPO in the presence
ꢀ
of TB(II).
Homogeneous photocatalytic systems with unique light-
driven redox properties have been studied extensively from the
viewpoint of artificial photosynthesis, but only a limited number
of examples of its application to organic synthesis have ap-
lyzed the oxidation of enamines leading to asymmetric C–C
bond formation.8 They developed organocatalysts to be com-
bined with the photoredox catalyst. In contrast, we have inten-
sively investigated the catalysis and energy transfer of TB(II).4
Herein, we report C–O bond formation based on the catalytic
oxidation of enamines by the photoactivated TB(II).
TB(II) has proven to effect oxidative coupling of 4-(3-phen-
yl-1-propenyl)morpholine (1a) with TEMPO at room tempera-
ture under irradiation with visible light (hꢁ > 420 nm), giving
ꢀ-oxyaminated aldehyde 3a in 84% isolated yield (Scheme 2).
Notably, the reaction did not proceed at all without visible light
irradiation, suggesting that the excited ꢀTB(II) species is in-
volved in this oxidative transformation.
It is remarkable to note that (1) the amount of TB(II) can be
reduced to a catalytic amount (2 mol %) and (2) 3-phenylpro-
pionaldehyde (2a) can be directly transformed into the oxyami-
nated product 3a in 56% isolated yield without prior conversion
to enamine 1a, when the reaction is carried out in the presence of
a catalytic amount of morpholine (20 mol %) (Table 1, Entry 1).9
Morpholine was essential to form the enamine intermediate in
situ (Entry 2). Addition of a small excess amount of amine
accelerated the conversion of aldehydes, while increasing the
amounts of unidentified by-products (Entry 3). This reaction
peared.1 Tris(bipyridyl)ruthenium(II) complex ([Ru(bpy)3]2þ
:
TB(II)) is one of the most investigated photocatalysts due to
its outstanding photo- and electrochemical properties originating
from metal-to-ligand charge transfer (MLCT).2 Its photosensiti-
zation effect related to catalysis is shown in Scheme 1.3 Visible
light irradiation of TB(II) forms the ꢀTB(II) species, which in the
presence of a sacrificial electron donor such as N(CH2CH2OH)3
and N(CH2CH3)3, is further converted to the reduced species
([Ru(bpy)3]þ: TB(I)) via single electron transfer. Thus the pho-
ꢀ
toexcited TB(II) is capable of 1e-oxidation of tertiary amines
including enamines.
We have developed some organometal-catalyzed reactions
using TB(II) and its derivatives as an energy-transfer reagent.4
However, the photocatalysis based on the above-mentioned sin-
gle electron oxidation of amines has been investigated to a lesser
extent, mainly because of the instability of the generated amine
radicals. We extended the photochemical oxidation to enamines
and found that photocatalytic reaction of enamines with 2,2,6,6-
tetramethylpiperidinyl-1-oxy (TEMPO) leading to ꢀ-oxyamina-
tion of carbonyl compounds. Oxyamination products are not
only useful as initiators of radical polymerization5 but also con-
vertible to diols through reductive transformation.6 Although the
oxidative transformation of enamines using excess oxidant such
as CAN and FeCl3 in the presence of cooxidants has been report-
ed,7 a catalytic oxidation process would be more attractive from
economic and environmental points of view. Recently, Nicewicz
and MacMillan have reported independently that TB(II) cata-
Table 1. Catalytic oxyamination of aldehydes with TEMPO
O
cat. morpholine (20 mol%)
cat. TB(II)•(PF6)2 (2 mol%)
1) CH3CNa, rt
O
O
N
R1
R1
H
+
H
R2
R2
O
1:1
h
ν
> 420 nm (Xe lamp)
TEMP
2) H2O
2a–2e
3a–3c
Entry
R1 R2
Time/h Isolated yield/%
1
2a: H CH2C6H5
24
15
15
15
24
24
24
24
3a: 56
2b
3c
4c,d
5
no reaction
3a: 45
3a: 40
3b: 68 (83e)
3c: 54
*TB(II)
NR3
2+
hν
N
NR3
N
N
N
Ru
N
2b: H (CH2)6CH3
N
TB(II)
TB(I)
6
7
8
2c: H (CH2)3CH=CH(C2H5)
2d: –(CH2)5–
2e: cyclohexanone
no reaction
no reaction
c
[Ru(bpy)3]2+:TB(II)
e–
a[carbonyl compound] = 0.1 M. bNo additive morpholine. 1.2 equiv
of morpholine was used. In DMF. Determined by 1H NMR.
d
e
Scheme 1. Photosensitization process of TB(II).
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.2 (2009)
167
O
Information11). These data suggests photoactivated TB can
easily oxidize 1e rather than TEMPO. Based on these results,
a possible catalytic cycle was proposed as summarized in
Scheme 4. First of all, morpholine reacts with aldehyde 2 to give
enamine 1. Then, 1 is 1e-oxidized by the photoactivated TB(II),
leading to the radical cation. Finally, radical coupling with
TEMPO gives the product 3, regenerating the morpholine by
hydrolysis afterward.
O
O
N
cat. TB(II)•(PF6)2 (2 mol%)
1) CH3CN, rt, 24 h
N
O
+
TEMP
1:1
h
ν
> 420 nm (Xe lamp)
2) H2O
1e
3e
81% yield
Scheme 3. Oxyamination of enamine derived from ketone.
In summary, we found ꢀ-oxyamination of aldehydes with
TEMPO using photoredox-active TB and morpholine as cata-
lysts. The present photoinduced oxidative transformation with
TB is a clean process that proceeds under mild conditions with
minimal metal waste. Further efforts to apply to asymmetric
oxidative transformation and to expand further the scope are
now underway.
proceeded equally well in CH3CN and DMF (Entries 3 and 4).
Other aldehydes 2b and 2c could be transformed under the same
reaction conditions to the corresponding coupling products 3b
and 3c (Entries 5 and 6). The (Z)-6-nonenal (2c) did not afford
cyclic compounds resulting from radical cyclization but linear
product 3c. On the other hand, the cyclohexanecarboxaldehyde
(2d) and cyclohexanone (2e) gave no ꢀ-oxyamination product
(Entries 7 and 8), suggesting that efficient formation of enamine
from secondary amine and carbonyl compounds seems to be cru-
cial for the progress of this oxidative reaction. In fact, the reac-
tion of 4-(1-cyclohexen-1-yl)morpholine (1e) gave the ꢀ-oxy-
aminated cyclohexanone (3e) in 81% yield (Scheme 3).10
Monitoring a CD3CN solution of nonanal (2b), TEMPO,
TB(II) (2 mol %), and morpholine (20 mol %) at room tempera-
ture by 1H NMR spectroscopy showed a rapid appearance of
two signals assigned to olefinic protons in the enamine at
5.8 ppm (3JHH ¼ 13 Hz, doublet) and 4.4 ppm (broad multiplet),
respectively. This result suggested a single isomer of the enam-
ine was efficiently formed under these conditions. As visible
light was irradiated to the reaction mixture, an increase of the
COCHOTEMP signal at 4.0 ppm was observed with the smooth
conversion of 2b to 3b. On the contrary, 3b was not observed at
all in the dark (see Supporting Information11), indicating that
irradiation of visible light promotes this oxidation.
References and Notes
1
2
S. Rau, D. Walther, J. G. Vos, Dalton Trans. 2007, 915.
a) A. Juris, V. Balzani, F. Barigelletti, S. Campagna, P. Belser, A.
von Zelewsky, Coord. Chem. Rev. 1988, 84, 85. b) V. Balzani, G.
Bergamini, F. Marchioni, P. Ceroni, Coord. Chem. Rev. 2006, 250,
1254, and references therein.
3
a) V. Balzani, L. Moggi, M. F. Manfrin, F. Bolleta, M. Gleria,
Science 1975, 189, 852. b) C. Creutz, N. Sutin, Proc. Natl. Acad.
U.S.A. 1975, 72, 2858. c) J. R. Bolton, Science 1978, 202, 705.
d) E. Borgarello, J. Kiwi, E. Pelizzetti, M. Visca, M. Graetzel, J.
¨
Am. Chem. Soc. 1981, 103, 6324. e) J.-M. Lehn, R. Ziessel, Proc.
Natl. Acad. Sci. U.S.A. 1982, 79, 701. f) R. Maidan, I. Willner, J.
Am. Chem. Soc. 1986, 108, 8100.
4
5
a) A. Inagaki, S. Edure, S. Yatsuda, M. Akita, Chem. Commun. 2005,
5468. b) M. Osawa, H. Nagai, M. Akita, Dalton Trans. 2007, 827.
c) A. Inagaki, S. Yatsuda, S. Edure, A. Suzuki, T. Takahashi, M.
Akita, Inorg. Chem. 2007, 46, 2432. d) A. Inagaki, H. Nakagawa,
M. Akita, K. Inoue, M. Sakai, M. Fujii, Dalton Trans. 2008, 6709.
a) C. J. Hawker, J. Am. Chem. Soc. 1994, 116, 11185. b) E. C.
Korolenko, F. L. Cozens, J. C. Scaiano, J. Phys. Chem. 1995, 99,
14123.
Although the reaction mechanism has not been clarified in
detail yet,12 photo- and electrochemical data supported the oxi-
dation of enamines by the photoactivated TB. Emission data
for TB(II) with 1e or TEMPO exhibited a decrease in emission
intensity of ꢀTB(II). Cyclic voltammetry data for 1e and
TEMPO showed an irreversible oxidation wave at +0.55 V and
a reversible redox wave at +0.62 V, respectively (see Supporting
6
7
D. L. Boger, R. M. Garbaccio, Q. Jin, J. Org. Chem. 1997, 62, 8875.
a) K. Narasaka, T. Okauchi, K. Tanaka, M. Murakami, Chem. Lett.
1992, 2099. b) T. D. Beeson, A. Mastracchio, J. Hong, K. Ashton,
D. W. C. MacMillan, Science 2007, 316, 582. c) M. P. Sibi, M.
Hasegawa, J. Am. Chem. Soc. 2007, 129, 4124. d) H. Jang, J. Hong,
D. W. C. MacMillan, J. Am. Chem. Soc. 2007, 129, 7004.
D. A. Nicewicz, D. W. C. MacMillan, Science 2008, 322, 77.
Typical experimental procedure is as follows: A 20-mL Schlenk
O
O
8
9
O
H
N
H
R
3
O
R
.
2
tube was charged with TEMPO (0.50 mmol), TB(II) (PF6)2
(0.010 mmol), and CH3CN (5 mL) under N2. After 2 (0.50 mmol)
had been introduced, morpholine (0.10 mmol) was added to the reac-
tion solution. Then, the tube was degassed. The reactions were
carried out at room temperature under irradiation of visible light
(hꢁ > 420 nm, Xe lamp at distance of 7 cm) for 24 h. The reaction
was quenched with exposure to air and NH4Cl (aq). The mixture
was extracted with CH2Cl2 and organic layer was dried over anhy-
drous MgSO4 and evaporated. The crude product was purified by
preparative TLC to give 3.
N
H
O
N
O
N
H2O
H
O
R
H
N
1
TB(I)
R
morpholine catalysis:
oxyamination cycle
e–
10 The reaction of 4-(cyclohexylidenemethyl)morpholine (1d) gave
some products which were also obtained from the reaction without
TEMPO. Characterization of products is now underway.
11 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
12 Especially, electron acceptor in the photosensitization process is un-
clear for now. We will report on the detailed mechanism in a forward
full paper.
photosensitization
TB(II)
O
N
O
N
O
N
h
ν
*TB(II)
H
H
R
R
Scheme 4. Possible reaction mechanism.
Published on the web (Advance View) January 17, 2009; doi:10.1246/cl.2009.166