Aerobic Copper–TEMPO Oxidation
FULL PAPER
Conclusions
Typical oxidation experiment for allylic substrates with CuBr
Geraniol 11 (1.54 g, 10.0 mmol, 100 mol%) was dissolved in acetonitrile
10 mL). Copper(II) bromide (0.067 g, 0.3 mmol, 3 mol%) was added,
2
ACHTUNGTRENNUNG( Table 2):
(
In conclusion, the effect of catalyst components in aerobic
copper–TEMPO oxidation of alcohols to carbonyl com-
pounds was studied. The amount of base is critical for the
outcome of the oxidation. Stoichiometric amounts of copper
and bipy should be used to ensure good activity. We found a
followed by bipy (0.047 g, 0.3 mmol, 3 mol%), transforming the colour to
brown and back to green. TEMPO (0.047 g, 0.3 mmol, 3 mol%) was
added to the reaction mixture, followed by N-methyl imidazole (0.049 g,
0.048 mL, 0.6 mmol, 6 mol%), giving a brown solution. Slight exother-
micity was observed after the reaction mixture was covered with oxygen
balloon. The reaction mixture was stirred at room temperature for one
hour (GC showed >99% conversion). The appearance of blue solids and
a colour change of the solution to green were observed. The reaction
mixture was partitioned between hexane (30 mL) and distilled water
1
.15-order kinetic correlation for TEMPO, and a 2.25-order
correlation for copper. We also found that these oxidations
follow a second-order dependency on the substrate alcohol
at low concentrations, and a first-order dependency on
oxygen at high alcohol concentrations. The copper(II) bro-
mide system was found to be a fast and mild method for al-
lylic alcohol oxidations. A catalytic system based on cop-
per(II) trifluoromethanesulfonate was suitable for more
challenging alcohol substrates. This methodology is more
active than previously described ones, and further studies
are warranted to elucidate its full potential.
(
30 mL). The aqueous phase was extracted with hexane (2ꢄ20 mL). The
combined organic extracts were washed with aqueous 0.5m H PO solu-
3
4
2 4
tion (30 mL) and brine (30 mL), dried with anhydrous Na SO and
evaporated to dryness to afford citral 12 as an oil (1.43 g, 94%). No fur-
ther purification was needed.
2
-Cyclohexylideneacetaldehyde (16): Synthesised according to typical pro-
[
35]
cedure with CuBr
2
from alcohol 15.
): d=10.01 (d, J=8.2 Hz, 1H), 5.82 (d, J=
.2 Hz, 1H), 2.70 (dd, J=5.4 Hz, 6.2 Hz, 2H), 2.29 (dd, J=5.3 Hz,
f
R =0.28 (20% EtOAc/hexanes);
1
H NMR (400 MHz, CDCl
3
8
1
3
6
.0 Hz, 2H), 1.60–1.76 ppm (m, 6H); C NMR (100 MHz, CDCl
3
): d=
1
90.3, 167.8, 125.0, 37.8, 29.3, 28.1, 27.9, 25.9 ppm. These data match
[
36]
those reported in the literature.
Typical oxidation experiment for non-activated substrates with Cu
(Table 3): 1-Decanol (19; 1.58 g, 10.0 mmol, 100 mol%) was dissolved in
acetonitrile (10 mL). Copper(II) trifluoromethanesulfonate (0.108 g,
.3 mmol, 3 mol%) was added, followed by bipy (0.047 g, 0.3 mmol, 3
mol%) to give a blue solution. TEMPO (0.047 g, 0.3 mmol, 3 mol%) was
added, transforming the colour to green. N-Methyl imidazole (0.025 g,
ACHTUNGTRENNUNG( OTf)
2
Experimental Section
AHCTUNGTRENNUNG
All commercial reagents were used without further purification. Acetoni-
trile (Rathburn HPLC grade, water content unknown) was used without
further purification. Other solvents were used as obtained from supplier,
unless otherwise noted. Merck 3 ꢂ molecular sieves were flame-dried
under high vacuum and kept in an oven (1208C). Analytical TLC was
performed using Merck silica gel F254 (10–12 mm) plates, and analysed by
UV light or by staining with PMA solution. For silica gel chromatogra-
phy, the flash chromatography technique was used, with Merck silica gel
0
0
3
.024 mL, 0.3 mmol, 3 mol%) and DBU (0.046 g, 0.045 mL, 0.3 mmol,
mol%) were added, giving a brown solution. The reaction flask was
covered with an oxygen balloon. After 15 min, 3 ꢂ molecular sieves
(1.5 g) were added. The reaction mixture was stirred at room tempera-
ture for 3 h. The colour was transformed first to green and then gradually
to blue. The reaction mixture was filtered through celite, and partitioned
between hexane (30 mL) and distilled water (30 mL). The aqueous phase
was extracted with hexane (2ꢄ20 mL). The combined organic extracts
6
0 (40–63 mm) and p.a. grade solvents unless otherwise noted. IR spectra
were recorded on a Perkin–Elmer Spectrum One spectrometer. Optical
rotations were obtained with a Perkin–Elmer 343 polarimeter. The
1
13
H NMR and C NMR spectra were recorded in CDCl
3
on a Bruker
Avance 400 ( H 399.98 MHz; C 100.59 MHz) spectrometer. The chemi-
cal shifts are reported in ppm relative to residual CHCl (d=7.26 ppm)
for H NMR. For the C NMR spectra, the solvent peak CDCl (d=
7.0 ppm) was used as the internal standard. Spectral data of the product
1
13
were washed with aqueous 0.5m H
3
PO
4
solution (30 mL) and brine
3
(
30 mL), dried with anhydrous Na SO
and evaporated to dryness to
2
4
1
13
3
afford decanal 20 as an oil (1.49 g, 95%). No further purification was
needed.
7
aldehydes were compared to commercially available compounds or to
the literature data. HRMS spectra were recorded on Waters LCT Pre-
mier spectrometer. Conversions were analysed with a Shimadzu GC-2010
gas chromatograph equipped with FID detector. The enantiomeric excess
3
-(tert-Butyldiphenylsilyloxy)propanal (24): Synthesised according to typ-
[
37]
ical procedure with Cu
gel chromatography.
A( OTf)
H
U
G
E
U
G
2
from alcohol 23 and purified with silica
1
R
f
=0.45 (20% EtOAc/hexanes); H NMR
(
400 MHz, CDCl
3
): d=9.82 (t, J=2.1 Hz, 1H), 7.63–7.69 (m, 4H), 7.35–
(
ee) of aldehyde 28 (RTmajor =26.18 min, RTminor =26.30 min) was deter-
7
.47 (m, 6H), 4.03 (t, J=5.9 Hz, 2H), 2.61 (dt, J=2.1 Hz, 6.0 Hz, 2H),
mined by GC using a Hewlett Packard HP 5890 instrument, Supelco b-
Dexꢃ 120 column (30 m ꢄ 0.25 mm, 0.25 mm film), using the gradient
1
3
3
1.05 ppm (s, 9H); C NMR (100 MHz, CDCl ): d=201.8, 135.5, 133.2,
ꢁ
1
method (708C, 4 min, 48Cmin
,
to 2208C), helium as carrier gas
30.6 cms ), with a Hewlett Packard 5971 MS detector (2708C).
Typical oxidation experiment for catalyst component study (Figures 1–
129.7, 127.7, 58.2, 46.3, 26.7, 19.1 ppm. These data match those reported
ꢁ
1
[38]
(
in the literature.
3-(4-Methoxybenzyloxy)propanal (26): Synthesised according to typical
[
39]
1
1
1
3): A standard solution of trans-2-hexen-1-ol 5 in acetonitrile (1.0 mmol,
00 mol%, 0.5m, 2 mL) and internal standard o-xylene (1.0 mmol,
00 mol%) in acetonitrile was added into a 25 mL round-bottomed flask
procedure with Cu
2
ACHTUNGTNERNGNU( OTf) from alcohol 25 and purified with silica gel
1
chromatography. R =0.40 (50% EtOAc/hexanes); H NMR (400 MHz,
f
CDCl
3
): d=9.78 (t, J=1.8 Hz, 1H), 7.22–7.28 (m, 2H), 6.85–6.91 (m,
equipped with magnetic stirrer bar. A solution of copper(II) bromide in
acetonitrile (0.02 mmol, 2 mol%; 20 mm, 1 mL) was added and the ensu-
ing mixture turned green. On addition of a solution of bipy in acetonitrile
2
1
1
H), 4.46 (s, 2H), 3.80 (s, 3H), 3.78 (t, J=6.0 Hz, 2H), 2.67 ppm (dt, J=
.8 Hz, 6.0 Hz, 2H); C NMR (100 MHz, CDCl ): d=201.1, 159.2, 129.9,
3
13
29.3, 113.8, 72.8, 63.4, 55.2, 43.8 ppm. These data match those reported
(
0.02 mmol, 2 mol%, 20 mm, 1 mL) the colour of the solution changed to
[40]
in the literature.
brown and then back to green. After 6 min, a solution of TEMPO in ace-
tonitrile (0.02 mmol, 2 mol%, 20 mm, 1 mL) was added without any sig-
N-Boc-l-valinal (28): Synthesised according to typical procedure with
Cu
A
H
U
G
R
N
N
(OTf)
2
from N-Boc-l-valinol 27. R
): d=9.64 (s, 1H), 5.09 (br s, 1H), 4.17–4.32
m, 1H), 2.15–2.38 (m, 1H), 1.45 (s, 9H), 1.03 (d, J=6.7 Hz, 3H),
f
=0.55 (50% EtOAc/hexanes);
nificant colour change. Finally,
a solution of DBU in acetonitrile
1
H NMR (400 MHz, CDCl
(
3
(
0.04 mmol, 4 mol%, 1m, 40 mL) was added, transforming the colour to
brown and gradually back to green. The reaction was stirred (500 rpm)
under an oxygen atmosphere (balloon) at room temperature. Samples
1
3
0.94 ppm (d, J=6.9 Hz, 3H); C NMR (100 MHz, CDCl
3
): d=200.1,
(
0.1 mL) were regularly taken and diluted with dichloromethane (1 mL)
155.6, 79.7, 64.4, 28.8, 28.0, 18.8, 17.3 ppm. These data match those re-
ported in the literature.
[
41]
for GC analysis.
Chem. Eur. J. 2009, 15, 10901 – 10911
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
10909