PAPER
Benzylic Oxidation Catalyzed by Hypervalent Iodine(III)
373
Anthraquinone (2e)
In summary, we have developed a novel and efficient
method for the oxidation of the benzylic C–H moiety of
alkylarenes with tert-butyl hydroperoxide and m-chloro-
peroxybenzoic acid in the presence of a catalytic amount
of (diacetoxyiodo)benzene in 2,2,2-trifluoroethanol at
room temperature. The corresponding aryl ketones were
obtained typically in good yields. This method has the ad-
vantages of mild reaction conditions and a simple experi-
mental procedure. Furthermore, the scope of hypervalent
iodine reagents in organic synthesis has been extended via
this approach.
Yield: 202 mg (97%); white solid; mp 279–281 °C (Lit.12 284–285
°C).
1H NMR (500 MHz, CDCl3): δ = 8.35–8.32 (m, 4 H), 7.84–7.81 (m,
4 H).
13C NMR (125 MHz, CDCl3): δ = 183.2, 134.1, 133.6, 127.3.
Acetophenone (2g)3g
Yield: 111 mg (93%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.69 (d, J = 5.0 Hz, 2 H), 7.29–
7.26 (m, 1 H), 7.18–7.15 (m, 2 H), 2.28 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 197.4, 136.9, 132.8, 128.3, 128.1,
26.2.
The alkylarenes, m-chloroperoxybenzoic acid, tert-butyl hydroper-
oxide and (diacetoxyiodo)benzene were commercially available.
Petroleum ether (PE) refers to the fraction boiling in the 60–90 °C
range. Melting points were measured with an XT-4 melting point
apparatus and are uncorrected. 1H NMR and 13C NMR spectra were
recorded on a Bruker Avance III (500M) spectrometer.
1-Phenylpropan-1-one (2h)4f
Yield: 83 mg (62%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.73 (d, J = 10.0 Hz, 2 H), 7.30–
7.27 (m, 1 H), 7.21–7.18 (m, 2 H), 2.71 (q, J = 10.0 Hz, 2 H), 0.98
(t, J = 10.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 200.0, 136.7, 132.6, 128.3, 127.7,
31.4, 7.9.
Benzylic Oxidation; General Procedure
To a soln of alkylarene 1 (1.0 mmol) in TFE (5 mL) were added
MCPBA (2.0 mmol), DIB (0.1 mmol) and TBHP (3.0 mmol). The
resulting mixture was stirred at r.t. for ca. 10 h (see Table 2). After
completion of the reaction, the solvent was evaporated under re-
duced pressure and then H2O (5 mL), sat. aq Na2S2O3 (2 mL) and
sat. aq Na2CO3 (2 mL) were added. The mixture was extracted with
CH2Cl2 (2 × 10 mL), then the combined organic extract was washed
with brine (10 mL), dried over anhyd MgSO4, filtered and concen-
trated under reduced pressure. The residue was purified on a silica
gel plate (PE–EtOAc, 20:1 or 10:1) to provide the corresponding
ketone 2.
1-Phenylbutan-1-one (2i)3g
Yield: 70 mg (47%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.97 (d, J = 5.0 Hz, 2 H), 7.56–
7.53 (m, 1 H), 7.47–7.41 (m, 2 H), 2.95 (t, J = 10.0 Hz, 2 H), 1.81–
1.74 (m, 2 H), 1.01 (t, J = 10.0 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 200.4, 137.1, 132.8, 128.5, 128.0,
40.5, 17.8, 13.9.
2-Methyl-1-phenylpropan-1-one (2j)13
Yield: 59 mg (40%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.98 (d, J = 5.0 Hz, 2 H), 7.58–
7.55 (m, 1 H), 7.50–7.47 (m, 2 H), 3.61–3.55 (m, 1 H), 1.24 (d,
J = 5.0 Hz, 6 H).
13C NMR (125 MHz, CDCl3): δ = 204.5, 136.3, 132.8, 128.6, 128.3,
35.4, 19.2.
Indan-1-one (2a)
Yield: 121 mg (92%); yellow solid; mp 42–44 °C (Lit.9 41–42 °C).
1H NMR (500 MHz, CDCl3): δ = 7.75 (d, J = 10.0 Hz, 1 H), 7.59–
7.56 (m, 1 H), 7.48–7.47 (m, 1 H), 7.38–7.34 (m, 1 H), 3.13 (t,
J = 10.0 Hz, 2 H), 2.69–2.67 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 207.0, 155.1, 137.1, 134.6, 127.3,
126.7, 123.7, 36.2, 25.8.
1-(4-Methoxyphenyl)ethanone (2k)
Yield: 95 mg (63%); white solid; mp 34–36 °C (Lit.14 37–39 °C).
3,4-Dihydronaphthalen-1(2H)-one (2b)8
Yield: 139 mg (95%); yellow oil.
1H NMR (500 MHz, CDCl3): δ = 8.04 (d, J = 5.0 Hz, 1 H), 7.50–
7.48 (m, 1 H), 7.32–7.24 (m, 2 H), 2.97 (t, J = 10.0 Hz, 2 H), 2.66
(t, J = 10.0 Hz, 2 H), 2.17–2.12 (m, 2 H).
1H NMR (500 MHz, CDCl3): δ = 7.94 (d, J = 10.0 Hz, 2 H), 6.94 (d,
J = 5.0 Hz, 2 H), 3.87 (s, 3 H), 2.56 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 196.7, 163.5, 130.6, 130.4, 113.7,
55.4, 26.3.
1-(4-Nitrophenyl)ethanone (2l)
13C NMR (125 MHz, CDCl3): δ = 198.3, 144.4, 133.3, 132.6, 128.7,
127.1, 126.6, 39.1, 29.7, 23.3.
Yield: 18 mg (11%); white solid; mp 47–49 °C (Lit.15 49 °C).
1H NMR (500 MHz, CDCl3): δ = 8.33 (d, J = 10.0 Hz, 2 H), 8.12 (d,
J = 10.0 Hz, 2 H), 2.69 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 196.3, 150.4, 141.4, 129.3, 123.9,
Fluoren-9-one (2c)
Yield: 155 mg (86%); yellow solid; mp 84–86 °C (Lit.10 82–83 °C).
1H NMR (500 MHz, CDCl3): δ = 7.68 (d, J = 5.0 Hz, 2 H), 7.55–
7.48 (m, 4 H), 7.32–7.28 (m, 2 H).
26.9.
Benzophenone (2m)
13C NMR (125 MHz, CDCl3): δ = 193.9, 144.5, 134.7, 134.2, 129.1,
124.3, 120.3.
Yield: 69 mg (38%); white solid; mp 46–47 °C (Lit.3g 46–48 °C).
1H NMR (500 MHz, CDCl3): δ = 7.82 (d, J = 10.0 Hz, 4 H), 7.61–
7.58 (m, 2 H), 7.51–7.47 (m, 4 H).
13C NMR (125 MHz, CDCl3): δ = 196.7, 137.6, 132.4, 130.1, 128.3.
Xanthen-9-one (2d)
Yield: 194 mg (99%); yellow solid; mp 173–175 °C (Lit.11 172–173
°C).
1H NMR (500 MHz, CDCl3): δ = 8.36 (d, J = 5.0 Hz, 2 H), 7.75–
7.72 (m, 2 H), 7.51 (d, J = 5.0 Hz, 2 H), 7.41–7.38 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 177.2, 156.2, 134.8, 126.7, 123.9,
(4-Nitrophenyl)(pyridin-4-yl)methanone (2n)
Yield: 25 mg (11%); white solid; mp 125–126 °C (Lit.16 121–122
°C).
1H NMR (500 MHz, CDCl3): δ = 8.89 (d, J = 10.0 Hz, 2 H), 8.39 (d,
121.9, 117.9.
J = 10.0 Hz, 2 H), 8.00 (d, J = 5.0 Hz, 2 H), 7.61 (d, J = 5.0 Hz, 2
H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 370–374