of Pd. However, to the best of our knowledge, no one-pot
and metal-free methods for the direct synthesis of aceto-
phenones from styrenes have been reported so far.
Scheme 1. Metal-Free Syntheses of Acetophenones from
Styrenes
Recently, we have developed various aerobic photo-
oxidations under an oxygen atmosphere and visible light
(VIS) irradiation.15 In addition, we reported the aerobic
photo-oxidative synthesis of phenacyl halides from styr-
enes in the presence of halogen sources.15c,i These methods
are of relevance from a viewpoint of green chemistry due to
the use of visible light from a general-purpose fluorescent
lamp, molecular oxygen being a terminal oxidant and
inexpensive, easily handled halogen sources such as mole-
cular iodine or 48% aq. HBr, and environmentally low
impact solvent use. Phenacyl halides are made known as a
versatile intermediate in organic synthesis and can be used
in various reactions. Representative of such reactions,
dehalogenations of phenacyl halides to acetophenone
using thiols,16 indium metal,17 bis(triphenylstannyl)-
selenide,18 PI3 or P2I4,19 catalytic telluride reagent/
reductant,20 hydroiodic acid,21 or iodide ion/Brønsted or
Lewis acids22 have been reported. In 2003, Horiuchi et al.23
reported that R-iodoketones were converted to R-hydro-
xyketones with UV irradiation under an air atmosphere
and found that R-iodoketones are deiodinated to ketones
under photoirradiation. These results prompted us to
study the direct transformation of styrenes to acetophe-
nones through one-pot aerobic photo-oxidation/deiodina-
tion. Our concept involves (1) aerobic photo-oxidation of
styrenes to phenacyl iodides and (2) exchange of solvent
and deiodination of phenacyl iodides to acetophenones.
These sequences can provide one-pot and metal-free
Wacker type oxidation of styrenes to acetophenones. In
the course of our effort, we found the facile deiodination of
phenacyl iodides withonly a catalytic amount of molecular
iodine in a small portion of acetone. Herein, we report the
one-pot metal-free synthesis of acetophenones from styr-
enes using molecular iodine (Scheme 1).
Table 1. Study of Reaction Conditions for Aerobic Photo-
oxidationa
solvent
(mL)
time
(h)
3a
(%)b
2a
(%)b
entry
1
EtOAc (5)
MeCN (5)
MeOH (5)
iPrOH (5)
THF (5)
10
10
10
10
10
10
10
10
10
10
10
10
10
3
71
2
3
2
73
3
68
1
4
63
3
5
73
2
6
hexane(5)
benzene(5)
CHCl3 (5)
H2O (5)
62
3
7
72
3
8
71
1
9
76
1
10
11c
12d
13e
14e
acetone (5)
acetone (5)
acetone (5)
acetone (5)
acetone (0.3)
trace
trace
trace
trace
trace
82
76
74
85
81
(15) (a) Kanai, N.; Nakayama, H.; Tada, N.; Itoh, A. Org. Lett. 2010,
12, 1948–1951. (b) Hirashima, S.; Nobuta, T.; Tada, N.; Miura, T.; Itoh,
A. Org. Lett. 2010, 12, 3645–3647. (c) Nobuta, T.; Hirashima, S.; Tada,
N.; Miura, T.; Itoh, A. Synlett 2010, 2335–2339. (d) Tada, N.; Ban, K.;
Hirashima, S.; Miura, T.; Itoh, A. Org. Biomol. Chem. 2010, 8, 4701–
4704. (e) Nobuta, T.; Hirashima, S.; Tada, N.; Miura, T.; Itoh, A.
Tetrahedron Lett. 2010, 51, 4576–4578. (f) Hirashima, S.; Itoh, A.
J. Synth. Org. Chem. Jpn. 2008, 66, 748–756. (g) Hirashima, S.; Itoh,
A. Photochem. Photobiol. Sci. 2007, 6, 521–524. (h) Hirashima, S.; Itoh,
A. Green Chem. 2007, 9, 318–320. (i) Nakayama, H.;Itoh, A. Tetrahedron
Lett. 2007, 48, 1131–1133. (j) Nakayama, H.; Itoh, A. Chem. Pharm. Bull.
2006, 54, 1620–1621.
(16) (a) Fuji, K.; Node, M.; Kawabata, T.; Fujimoto, M. J. Chem.
Soc., Perkin Trans. 1 1987, 1043–1047. (b) Fuji, K.; Node, M.;
Kawabata, T.; Fujimoto, M. Chem. Lett. 1984, 1153–1156. (c) Seshadri,
R.; Pegg, W. J.; Israel, M. J. Org. Chem. 1981, 46, 2696–2598.
(17) (a) Pauk, L.; Keum, G.; Kang, S. B.; Kim, K. S.; Kim, Y.
J. Chem. Soc., Perkin Trans. 1 2000, 4462–4463. (b) Ranu, B. C.; Dutta,
P.; Sarkar, A. J. Chem. Soc., Perkin Trans. 1 1999, 1139–1140.
(18) Schultz, E. K. V.; Harpp, D. N. Synthesis 1998, 1137–1140.
(19) Denis, J. N.; Krief, A. Tetrahedron Lett. 1981, 22, 1431–1432.
(20) Huang, Z. Z.; Tang, Y. J. Org. Chem. 2002, 67, 5320–5326.
(21) (a) Penso, M.; Mttadelli, S.; Albanese, D. Synth. Commun. 1993,
23, 1385–1391. (b) Mandal, A. K.; Nijasure, A. M. Synlett 1990, 554.
(22) (a) Ono, A.; Kamimura, J.; Suzuki, N. Synthesis 1987, 406–407.
(b) Gemal, A. L.; Luche, J. L. Tetrahedron Lett. 1980, 3195–3198. (c)
Olah, G. A.; Arvanaghi, M.; Vankar, Y. D. J. Org. Chem. 1980, 45,
3531–3532. (d) Townsend, J. M.; Spencer, T. A. Tetrahedron Lett. 1971,
137–140.
a A solution of 4-tert-butylstyrene (1a; 0.3 mmol), iodine (0.6 equiv),
and H2O (80 μL) in EtOAc (3 mL) under an O2 atmosphere was stirred
and irradiated externally with four 22 W fluorescent lamps. After 10 h,
the reaction mixture was concentrated in vacuo and solvent was added
and stirred for the indicated time. b 1H NMR yields. c The reaction was
carried out under a N2 atmosphere in the deiodination step. d The
reaction was carried out in the dark in the deiodination step. e The
reaction was carried out under air and negative irradiation in the
deiodination step.
Table 1 shows the results involving optimization of
reaction conditions for aerobic photo-oxidation/deiodina-
tion of 4-tert-butylstyrene (1a) as a test substrate. The
reaction conditions were examined with 4-tert-butylstyr-
ene (1a) in the presence of iodine under an oxygen atmo-
sphere (O2 balloon) and VIS irradiation,15 followed by
concentration of the reaction mixture and addition of
solvent. Among the various solvents examined, only acet-
one was effective as a solvent for deiodination (entries
1ꢀ10), and the corresponding acetophenone (2a) was
obtained in good yield (entry 10). Furthermore, we found
(23) (a) Chi, W.; Takeda, A.; Hara, M.; Ji, S. J.; Horiuchi, C. A.
Tetrahedron 2005, 61, 2453–2463. (b) Horiuchi, C. A.; Takeda, A.; Chi,
W.; Ohwada, K.; Ji, S. J.; Takahashi, T. T. Tetrahedron Lett. 2003, 44,
9307–9311.
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