Selective aerobic oxidation of allylic and benzylic alcohols catalyzed by N-hydroxyindole and copper(I) chloride

Article abstract of DOI:10.1016/j.tetlet.2011.12.058

In the presence of copper(I) chloride, tert-butyl 1-hydroxy-2-methyl-6- trifluoromethyl-1H-indole-3-carboxylate acted as a catalyst for the chemoselective aerobic oxidation of allylic and benzylic alcohols. A variety of primary and secondary allylic and benzylic alcohols were oxidized into the corresponding α,β-unsaturated carbonyl compounds in good yields without affecting non-allylic alcohols.

Full text of DOI:10.1016/j.tetlet.2011.12.058

Tetrahedron Letters 53 (2012) 986–990
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Tetrahedron Letters
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Selective aerobic oxidation of allylic and benzylic alcohols catalyzed
by N-hydroxyindole and copper(I) chloride
⇑
Shu-Su Shen, Vita Kartika, Ying Shan Tan, Richard D. Webster, Koichi Narasaka
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
In the presence of copper(I) chloride, tert-butyl 1-hydroxy-2-methyl-6-trifluoromethyl-1H-indole-3-car-
boxylate acted as a catalyst for the chemoselective aerobic oxidation of allylic and benzylic alcohols. A
variety of primary and secondary allylic and benzylic alcohols were oxidized into the corresponding
Received 18 October 2011
Revised 6 December 2011
Accepted 16 December 2011
Available online 24 December 2011
a
,b-unsaturated carbonyl compounds in good yields without affecting non-allylic alcohols.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Selective aerobic oxidation
Allylic alcohol
Benzylic alcohol
N-Hydroxyindole
Chemoselective oxidation of allylic and benzylic alcohols plays a
key role in organic synthesis, and many catalytic methods have been
developed employing different oxidants,1 such as oxone,1b iodine,1c
and DDQ.1d In order to replace these oxidizing reagents with
oxygen, aerobic oxidation methods have been explored using tran-
sition metal complexes of Pd,2 Ru,3 or Ir4 as catalysts. In addition,
nitroxides (nitroxyls),5 such as 2,2,6,6-tetramethylpiperidyl-1-oxyl
(TEMPO) and 2-azaadamantane-N-oxyl (AZADO),6 were applied for
the aerobic oxidation of alcohols. However, these nitroxides exhibit
strong reactivity and are not suitable for the chemoselective oxida-
tion of allylic alcohols. Among nitroxides, 2,2,4,4-tetramethyloxaz-
olidine-N-oxyls (TOXYLs) catalyze the oxidation of allylic alcohols
selectively, however, this method requires a very long reaction time
and is applicable only to the oxidation of primary examples.7
We recently became interested in the use of N-hydroxyindoles
(NHIs) as catalysts for the chemoselective aerobic oxidation of
allylic alcohols, envisioning that the N–OH group may act as the
precursor of nitroxy radicals and/or oxoammonium species, which
are highly conjugated and readily tuned-up by substituents on the
indole moiety. As such species were expected to act as mild oxi-
dants, our work started by comparing the efficiencies of NHIs listed
in Figure 1.8
having electron-withdrawing substituents catalyzed the oxidation
more effectively than NHIs bearing electron-donating R3 groups
(NHI-1 to NHI-6). The introduction of a bulky R1 group at the C2
position of the indole slowed down the rate of oxidation (Table
1, NHI-7, 10). Although all these N-hydroxyindoles catalyzed the
aerobic oxidation of 11a, tert-butyl 1-hydroxy-2-methyl-6-trifluo-
romethyl-1H-indole-3-carboxylate (NHI-1) was found to be the
best catalyst.
From cyclic voltammetry measurements of NHI-1, 4, and 5,
NHI-1 exhibited a higher Epa (+0.589 V) value compared with those
of NHI-4 and NHI-5 (+0.463 and +0.418 V, respectively). These re-
sults are consistent with the efficiency of these catalysts, in which
NHI-1 exhibited high catalytic activity. After screening the reaction
R1 = Me
R1 = Me
R1 = Me
R1 = Me
R1 = Me
R1 = Me
R1 = i-Pr
R1 = Me
R1 = H
R2 = COOtBu R3 = 6-CF3
NHI-1
NHI-2
NHI-3
NHI-4
NHI-5
COOtBu
COOtBu
COOtBu
2
R =
R3 = 6-Br
R3 = 6-F
R3 = 5-F
2
R2
R =
2
R =
R1
R3
R2 = COOtBu R3 = H
N
OH
6
NHI-
R2 =
R3 = Me
t
COO Bu
The oxidation of 3,5,5-trimethylcyclohex-2-enol (11a) was
examined using catalytic amounts of NHIs and CuCl under an oxy-
gen atmosphere9 and the results are summarized in Table 1. NHIs
NHI
NHI-7
NHI-8
NHI-9
R2 = COOtBu R3 = H
R2 = COOEt
R2 = COOEt
R3 = H
R3 = H
NHI-10 R1 = COOtBu R2 = COOtBu R3 = H
⇑
Corresponding author. Tel.: +65 6316 8900; fax: +65 6791 1961.
E-mail address: narasaka@ntu.edu.sg (K. Narasaka).
Figure 1. Structures of the N-hydroxyindoles (NHIs).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.12.058

S.-S. Shen et al. / Tetrahedron Letters 53 (2012) 986–990
987
conditions using NHI-1 and CuCl, DMF was found to be the most
suitable solvent, and both NHI and CuCl were necessary for this
aerobic oxidation. Next, the scope and limitations of this process
were explored using the optimized conditions: NHI-1 (10 mol %)
and CuCl as catalysts in DMF at 50 °C under an atmospheric pres-
sure of oxygen.
Various secondary benzylic and allylic alcohols 11 were investi-
gated as summarized in Table 2. Benzylic alcohols 11b and 11c
were oxidized smoothly to the corresponding ketones even on
reducing the catalyst loading to 5 mol % (entries 2 and 3). Cyclic
and acyclic secondary allylic alcohols were oxidized to afford
b-isomer 11h (3 hours, 81% yield). The oxidation of less active
stereoisomer 11g could be accelerated (6 h, 72% yield) by
modification of the catalytic conditions (30 mol % of NHI-1 and
CuCl, 80 °C), whereas trans-11f (trans/cis >91:9) resisted full oxida-
tion to the corresponding ketone (44 h, 27% yield).
Thus, chemoselective aerobic oxidations of sec-allylic and ben-
zylic alcohols were accomplished using the catalytic NHI-1/CuCl
system. Under these catalytic conditions, allylic and benzylic pri-
mary alcohols 11k–p could be transformed into aldehydes 12k–o
in good yields (Table 3). However, a non-allylic primary alcohol,
3-phenylpropan-1-ol (11p) could not be oxidized to 3-phenylprop-
anal even after two days (entry 6). During the oxidation of primary
allylic alcohols, small amounts of the corresponding carboxylic
acids 13 were detected as side products. The formation of these
acids could not be suppressed completely, since the aldehydes
underwent facile autoxidation to carboxylic acids under the pres-
ent conditions.
In order to check whether dioxygen was incorporated into the
resulting carbonyl compounds, the aerobic oxidation was con-
ducted under an 18O2 atmosphere. When the oxidation of 1,2,3,4-
tetrahydronaphthalen-1-ol (11b) was examined under 18O2, no
introduction of 18O was observed in product 12b. This indicates
that the carbonyl oxygen of the ketone 12b must originate from
the hydroxy group of the alcohol 11b. Based on this result, the fol-
lowing two routes may be proposed for the oxidation. Firstly, the
CuCl–O2 complex11 oxidizes NHI-1 to the corresponding oxoam-
monium cation6,12 (Scheme 3, path A), which oxidizes the allylic
alcohols. Another possibility is the formation of an N-oxyl radical
from NHI-1 (Scheme 3, path B), which abstracts an allylic hydrogen
a,b-unsaturated ketones in good isolated yields (entries 1, 4–6).
In contrast, the oxidation of non-allylic alcohol 11j proceeded at
an extremely slow rate to give 12j in 5% and 17% yields after 5
and 17 h, respectively (entry 7). Accordingly, in the oxidation of
diol 11i (entry 6), only the allylic alcohol moiety was oxidized.10
Thus, chemoselective oxidation (allylic vs non-allylic) was realized
by applying the present method.
As another characteristic of this method, a significant reactivity
difference was observed in the oxidation of stereoisomers of cyclic
allylic alcohols. For example, when a cis/trans (1/1 mixture) of
(5R)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enol (11f) was sub-
jected to the oxidation conditions, ketone 12f was obtained in a
42% yield after 24 h, but 45% of trans-11f was recovered (Scheme
1). In fact, oxidation of cis-11f (cis/trans >95:5) afforded ketone
12f in an 86% yield after 24 h together with 3% recovery of trans-
11f, whereas trans-11 (trans/cis >93:7) was oxidized very slowly
(48 h, 23% yield).
In addition, significant differences were sometimes observed in
the oxidation of secondary cyclic allylic alcohols. It took longer to
to generate an a-hydroxy allylic radical. This allylic radical is then
oxidize the
a-isomer of cholest-4-en-3-ol (11g) to (+)-4-cholesten-
oxidized to an allylic cation, followed by deprotonation to give the
3-one (12g) (Scheme 2 and 24 h, 76% yield) compared with the
carbonyl compound.
Table 1
Optimization of the reaction conditionsa
OH
O
NHI-1 / CuCl (x mol%)
Me
Me
Me
Me
solvent (0.5 M)
O2 (1 atm)
Me
Me
11a
12a
Entry
NHI
x (mol %)
Solvent
Time (h)
Conv.b (%)
Yieldb (%)
1
2
3
4
5
6
7
8
NHI-1
NHI-2
NHI-3
NHI-4
NHI-5
NHI-6
NHI-7
NHI-8
NHI-9
NHI-10
NHI-1
NHI-1
NHI-1
NHI-1
NHI-1
NHI-1
NHI-1
NHI-1
NHI-1
NHI-1
10
10
10
10
10
10
10
10
10
10
5
10
10
10
10
10
10
10
10
10
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
DCE
4
4
4
4
4
4
4
4
4
4
4
12
4
4
4
4
4
97
89
82
84
79
76
62
82
66
74
75
89
38
59
32
89
30
62
<1
<1
93
75
73
74
64
65
60
76
61
64
64
52
29
33
20
73
30
56
—
9
10
11
12c
13
14
15
16
17
18
19d
20e
CH2Cl2
CH3CN
Toluene
CH3OH
DMF
4
24
24
DMF
—
a
b
c
All reactions were performed using alcohol (0.25 mmol) in DMF (0.5 mL) at 50 °C.
Determined by GC analysis using biphenyl as an internal standard.
Reaction was run at room temperature.
Reaction was run using 10 mol % NHI-1 without CuCl.
Reaction was run using 10 mol % CuCl without NHI-1.
d
e

988
S.-S. Shen et al. / Tetrahedron Letters 53 (2012) 986–990
Table 2
NHI-1 and CuCl-catalyzed oxidation of secondary allylic and benyzlic alcoholsa
R'
R'
10 mol% NHI-1 /CuCl
R
OH
R
DMF (0.5 M), 50 °C
O2 (1 atm)
O
11
12
Entry
1
Alcohol
Time (h)
Ketone
Yieldb (%)
OH
OH
O
O
11a
12
12a
83
Me
Me
Me
Me
Me
Me
2c
3c
11b
11c
10
16
12b
12c
92
91
OH
O
Me
OH
Me
4
5
11d
11e
8
12d
12e
84
76
Ph
Ph
O
Me
OH
Me
15
n-C10H21
n-C10H21
O
OH
OH
H
H
Me
Me
H
t
t
OSiMe2 Bu
OSiMe2 Bu
H
Me
H
Me
6
7
11i
11j
5
12i
12j
90
H
H
H
HO
Ph
O
OH
Me
O
5
5
Ph
Me
60
17
a
b
c
All reactions were carried out using alcohol (2.0 mmol) in DMF (4 mL), except for 11i (0.4 mmol) in DMF (1.6 mL).
Isolated yield.
5 mol % catalyst loading.
Me
Me
Me
Me
H
Me
H
OH
O
OH
10 mol% NHI-1/CuCl
R
Me
H
DMF, 50 °C
O2 (1 atm)
Me
H
Me
H
Me
11f
(cis/ trans = 1:1)
Me
12f
42% yield
R
Me
trans-11f
recovery 45%
11g
24 h
(24 h, 76% yield)
HO
HO
Me
H
Me
H
H
H
Me
H
O
R
11f
cis-
(cis/tr ans > 95:5)
12f
86% yield
11f
tr ans-
recovery 3%
12g
R = (CH2)3CHMe2
Me
H
24 h
H
trans-11f
(tr ans/cis > 93:7)
12f
23% yield
trans-11f
recovery 33%
11h (3 h, 81% yield)
-ol (11g) and cholest-4-en-3b-ol (11h).
48 h
Scheme 2. Oxidation of cholest-4-en-3
a
Scheme 1. Oxidation of (5R)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enol (11f).
Oxidations were performed using alcohol (2 mmol) in DMF (4 mL) at 50 °C under
the optimized reaction conditions, except for that of trans-11f which was
performed on 1 mmol scale.
Oxidations were performed using 11g (0.1 mmol) in DMF (0.4 mL) and 11h
(0.5 mmol) in DMF (2 mL), respectively.
acetoacetate,13 was found to act as a highly chemoselective catalyst
for the aerobic oxidation of primary and secondary allylic and ben-
zylic alcohols in the presence of copper(I) chloride as a co-catalyst.14
In conclusion, tert-butyl 1-hydroxy-2-methyl-6-(trifluoro-
methyl)-1H-indole-3-carboxylate (NHI-1), which is readily prepared
from 1-fluoro-2-nitro-4-trifluoromethylbenzene and tert-butyl

S.-S. Shen et al. / Tetrahedron Letters 53 (2012) 986–990
989
Table 3
2. (a) Kaneda, K.; Fujii, M.; Morioka, K. J. Org. Chem. 1996, 61, 4502–4503; (b)
Peterson, K. P.; Larock, R. C. J. Org. Chem. 1998, 63, 3185–3189; (c) Schultz, M. J.;
Adler, R. S.; Zierkiewicz, W.; Privalov, T.; Sigman, M. S. J. Am. Chem. Soc. 2005,
127, 8499–8507; (d) Steinhoff, B. A.; Guzei, I. A.; Stahl, S. S. J. Am. Chem. Soc.
2004, 126, 11268–11278.
NHI-1 and CuCl-catalyzed oxidation of primary allylic and benzylic alcoholsa
10 mol% NHI-1 /CuCl
COOH
13
R
R
OH
O
R
DMF (0.5 M), 50°C
O2 (1 atm)
3. Kaneda, K.; Yamashita, T.; Matsushita, T.; Ebitani, K. J. Org. Chem. 1998, 63,
1750–1751.
11
12
4. (a) Arita, S.; Koike, T.; Kayaki, Y.; Ikariya, T. Angew. Chem., Int. Ed. 2008, 47,
2447–2449; (b) Jiang, B.; Feng, Y.; Ison, E. A. J. Am. Chem. Soc. 2008, 130, 14462–
14464.
5. For nitroxy radical catalyzed alcohol oxidations, see: (a) Sheldon, R. A.; Arends,
I. W. C. E. Adv. Synth. Catal. 2004, 346, 1051–1071; (b) de Nooy, A. E. J.; Besemer,
A. C.; van Bekkum, H. Synthesis 1996, 1153–1174.
6. For AZADO derivative catalyzed oxidations, see: (a) Shibuya, M.; Osada, Y.;
Sasano, Y.; Tomizawa, M.; Iwabuchi, Y. J. Am. Chem. Soc. 2011, 133, 6497–6500;
(b) Shibuya, M.; Tomizawa, M.; Suzuki, I.; Iwabuchi, Y. J. Am. Chem. Soc. 2006,
128, 8412–8413; (c) Shibuya, M.; Tomizawa, M.; Sasano, Y.; Iwabuchi, Y. J. Org.
Chem. 2009, 74, 4619–4622; (d) Shibuya, M.; Sato, T.; Tomizawa, M.; Iwabuchi,
Y. Chem. Commun. 2009, 1739–1741.
Entry Alcohol
Time (h) Aldehydeb (%) Acidb (%)
OH
1
11k 11
12k (85)
12l (75)
13k (13)
13l (9)
MeO
OH
OH
2
3
11l
12
11m 24
12m (65)
13m (13)
7. Gartshorea, C. J.; Lupton, D. W. Adv. Synth. Catal. 2010, 352, 3321–3328.
8. For the preparation of these N-hydroxylindoles, see: (a) Belley, M.; Beaudoin,
D.; St-Pierre, G. Synlett 2007, 2999–3002; (b) Belley, M.; Beaudoin, D.; Duspara,
P.; Sauer, E.; St-Pierre, G.; Trimble, L. A. Synlett 2007, 2991–2994; (c) Wróbel,
Z.; Ma˛kosza, M. Tetrahedron 1997, 53, 5501–5514.
9. For nitroxyl radicals in Cu(I)- or Cu(II)-catalyzed aerobic oxidations of alcohols,
see: (a) Kitajima, N.; Whang, K.; Moro-oka, Y.; Uchida, A.; Sasada, Y. J. Chem.
Soc. 1986, 1504–1505; (b) Wang, Y.; Stack, T. D. P. J. Am. Chem. Soc. 1996, 118,
13097–13098; (c) Wang, Y.; Du Bois, J. L.; Hedman, B.; Hodgson, K.; Stack, T. D.
P. Science 1998, 279, 537–540; (d) Chaudhuri, P.; Hess, M.; Flörke, U.;
Wieghardt, K. Angew. Chem., Int. Ed. 1998, 37, 2217–2220; (e) Mahadevan, V.;
Du Bois, J. L.; Hedman, B.; Hodgson, K.; Stack, T. D. P. J. Am. Chem. Soc. 1999, 121,
5583–5584; (f) Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chou, S. J. Am.
Chem. Soc. 1984, 106, 3374–3376; (g) Dijksman, A.; Arends, I. W. C. E.; Sheldon,
R. A. Org. Biomol. Chem. 2003, 1, 3232–3237.
4c
11n 24
11o 18
11p 48
12n (62)
12o (52)
N.R.d
13n (14)
13o (12)
n-C10H21
OH
5
Ph
OH
OH
6
Ph
a
b
c
All reactions were carried out using alcohol (2.0 mmol) in DMF (4 mL).
Isolated yield.
4% of (E)-4-oxotridec-2-enal (15n) was isolated.
No reaction.
d
10. TEMPO (10 mol %) and CuCl (10 mol %) in DMF was used for the oxidation of
diol 11i at 50 °C, chemoselective oxidation of the allylic alcohol occurred, but
gave a 23% yield of 12i after 24 h (37% yield, 48 h).9f (b) Oxidation of 11i with
TEMPO (10 mol %), NaOCl (150 mol %), KBr (10 mol %), Bu4NBr (5 mol %), aq
NaHCO3 in CH2Cl2 at 0 °C was also tested but afforded ketone 12i in only 50%
yield although 11i was completely consumed. (c) Anelli, P. L.; Banfi, C.;
Montanari, F.; Quici, S. J. Org. Chem. 1987, 52, 2559–2562.
11. Lucas, H. R.; Li, L.; Narducci Sarjeant, A. A.; Vance, M. A.; Solomon, E. I.; Karlin,
K. D. J. Am. Chem. Soc. 2009, 131, 3230–3245.
12. de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Tetrahedron 1995, 51, 8023–
8032.
t
COO Bu
-H+
OH
R'
12
12
COOtBu
Me
R
R
Me
N
OH
F3C
Cu(II)
NHI-1
N
F3C
OH
R'
O
O
R
H
13. Typical procedure for tert-Butyl 1-hydroxy-2-methyl-6-trifluoromethyl-1H-
indole-3-carboxylate (NHI-1): At 0 °C, tert-butyl acetoacetate (6.62 mL,
R'
path B
R
path A
COOtBu
Me
40 mmol) was added dropwise to
42 mmol) in dry THF (200 mL) under a nitrogen atmosphere. The mixture
was left to stir at 0 °C until clear solution formed. 1-Fluoro-2-nitro-4-
a suspension of NaH (60%) (1.68 g,
11
a
Cu(I)-O2
COOtBu
trifluoromethylbenzene (2.8 mL, 20 mmol) was added dropwise and the
mixture was allowed to stir under reflux. After consumption of the starting
material (7 h), the mixture was cooled to room temperature and quenched
with H2O (300 mL) and extracted with EtOAc (50 mL Â 3). The extracts were
dried over anhydrous MgSO4, filtered and evaporated under reduced pressure.
The crude residue was purified by flash column chromatography (silica gel;
hexane–EtOAc = 250: 1) to give (E)-tert-butyl 3-hydroxy-2-(2-nitro-4-
trifluoromethylphenyl)but-2-enoate (14a) as a yellow oil (6.47 g, 18.6 mmol,
N
F3C
H
C
O
O
R'
Me
H
Cu
N
F3C
COOt Bu
Me
O
oxoammonium cation
93% yield) as
a mixture of enol (major) and ketone (minor) isomers as
11
N
O
determined from the NMR spectrum. Yellow oil, 1H NMR (400 MHz, CDCl3) d
13.26 (0.94H, OH, s), 8.30 (0.06H, s), 8.23 (0.94H, s), 7.88 (0.06H, dd, J = 1.2 Hz,
8.0 Hz), 7.82 (0.94H, dd, J = 1.2 Hz, 8.0 Hz), 7.66 (0.06H, d, J = 8.0 Hz), 7.44
(0.94H, d, J = 8.0 Hz), 5.30 (0.06H, s), 2.44 (0.18H, s), 1.90 (2.82H, s), 1.49
(0.54H, s), 1.34 (8.46H, s); 13C NMR (100 MHz, CDCl3) d 173.27, 169.95, 149.69,
134.72, 134.51, 130.72 (q, J = 34 Hz), 128.97 (q, J = 3 Hz), 124.21, 121.56 (q,
F3C
2
O
-
I)
(
u
C
Scheme 3. Two proposed mechanistic pathways.
J = 4 Hz), 101.35, 83.12, 27.82 (3 C), 20.02; IR (KBr)
m 3020, 2982, 1645, 1539,
Acknowledgments
1354, 1323, 1152 cmÀ1; HRMS (ESI) calcd for C15H17F3NO5 [M+H]+: 348.1059,
found: 348.1055. In the next step, to 5% Pd/C (1.7 g, 0.82 mmol) in a flask was
added EtOAc (20 mL) and Pd(PPh3)4 (0.19 g, 0.016 mmol), followed by 14a
(5.7 g, 16.42 mmol) in EtOAc (40 mL) and AcOH (15 mL). The reaction mixture
was degassed and changed to a hydrogen balloon (1 atm). The mixture was
allowed to stir at room temperature until complete (12 h). The mixture was
filtered through Celite and rinsed with EtOAc. The solvents were removed
under reduced pressure and the residue was purified by flash column
chromatography (silica gel; hexane–EtOAc = 8: 1) to give pure tert-butyl 1-
This work was supported by funding from Nanyang Technolog-
ical University and Singapore Ministry of Education.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.12.058.
hydroxy-2-methyl-6-trifluoromethyl-1H-indole-3-carboxylate (NHI-1) as
a
white solid (4.21 g, 80% yield). Mp 163–165 °C, 1H NMR (400 MHz, DMSO-d6)
d 11.91 (1H, OH, s), 8.14 (1H, d, J = 8.4 Hz), 7.74 (1H, s), 7.46 (1H, d, J = 8.4 Hz),
2.69 (3H, s), 1.59 (9H, s); 13C NMR (100 MHz, DMSO-d6) d 163.66, 144.19,
131.70, 124.99 (q, J = 270 Hz), 124.70, 122.25 (q, J = 31.5 Hz), 121.13, 117.60 (d,
References and notes
J = 3 Hz), 105.77 (d, J = 4 Hz), 99.78, 79.55, 28.19 (3C), 10.56; IR (KBr)
3071, 1643, 1537, 1448, 1333, 1163, 1120 cmÀ1
HRMS (ESI) calcd for
15H17F3NO3 [M+H]+: 316.1161, found: 316.1169. The structure of NHI-1 was
established by X-ray crystallographic analysis (see Supplementary data), CCDC
818557 contains the supplementary crystallographic data for compound NHI-
1. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/
m 3090,
1. For the oxidation of allylic alcohols by transition metals, see: (a) Uma, R.;
Crévisy, C.; Grée, R. Chem. Rev. 2003, 103, 27–51. and references therein; (b)
Bolm, C.; Magnus, A. S.; Hildebrand, J. P. Org. Lett. 2000, 2, 1173–1175; (c)
Miller, R. A.; Hoerrner, R. S. Org. Lett. 2003, 5, 285–287; (d) Cosner, C. C.;
Cabrera, P. J.; Byrd, K. M.; Thomas, A. M. A.; Helquist, P. Org. Lett. 2011, 13,
2071–2073; (e) Hanson, S. K.; Wu, R.; Silks, L. A. Org. Lett. 2011, 13, 1908–1911.
;
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conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12
progress was monitored by TLC or GC. After completion, the mixture was
allowed to cool to room temperature, quenched with 1 M HCl, diluted with
H2O (50 mL), and extracted with EtOAc (10 mL Â 3). The combined organic
layer was washed with brine and dried over MgSO4, the crude was purified by
flash column chromatography (EtOAc–hexane = 1:10 to 1:3) to afford ketone or
aldehyde 12 and NHI-1 (70% recovery). 3,5,5-Trimethylcyclohex-2-enone
(12a): Colorless oil, 1H NMR (400 MHz, CDCl3) d 5.89 (1H, s), 2.19 (2H, s),
2.17 (2H, s), 1.94 (3H, s), 1.04 (6H, s).
Union Road, Cambridge, CB2 1EZ, UK; fax: (+44)1223-336-033; or
deposit@ccdc.cam.ac.uk).
14. General procedure for selective aerobic oxidation of allylic and benzylic
alcohols: To 10 mL Schlenk tube, NHI-1 (0.2 mmol, 63 mg) and CuCl
a
(0.2 mmol, 19.6 mg) and DMF (2 mL) were added and stirred at 50 °C for
about 30 min to form a dark red solution. Alcohol 11 (2 mmol) was added. The
mixture was left to stir at 50 °C under an oxygen balloon (1 atm). The reaction