PAPER
Oxidation with 4-Acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium Tetrafluoroborate
2493
Table 2 1H NMR Spectra of 5a–k
R1
R2
+
R1
R2
H
N
+
N
+
O
+
HO
H
OH
Aldehyde 5 1H NMR (200 MHz, CDCl3/TMS) d, J (Hz)
O
primary product,
final when py is absent
5a
0.80–1.10 (m, 3 H, CH3), 1.12–1.76 (m, 18 H, 9 CH2),
1.86–2.16 (m, 4 H, 2 CH2CH=), 2.28–2.50 (m, 2 H,
CH2CHO), 5.26–5.48 (m, 2 H, CH=CH), 9.76 (t, 1 H,
J = 1.9, CHO)
py
N
O
final product
when py is present
5b
1.16–1.74 (m, 8 H, 4 CH2), 1.88–2.14 (m, 2 H,
CH2CH=), 2.43 (dt, 2 H, J = 1.8, 7.2, CH2CHO), 4.84–
5.08 (m, 2 H, CH2=), 5.68–5.92 (m, 1 H, CH=), 9.77 (t,
1 H, J = 1.8, CHO)
Scheme 2 Two-electron oxidation process in the absence or in the
presence of pyridine
5c
1.20–1.80 (m, 8 H, 4 CH2), 1.94 (t, 1 H, J = 2.6, CH≡),
2.19 (dt, 2 H, J = 2.6, 6.8, CH2C≡), 2.28–2.52 (m, 2 H,
CH2CHO), 9.77 (t, 1 H, J = 1.8, CHO)
The oxidation of primary alcohols (unsaturated and/or
containing halogen atom) used in insect pheromone syn-
thesis results in corresponding aldehydes with good
yields, in general, better than with PCC. The oxidation re-
action is performed in the presence of silica gel as cata-
lyst. The end of the reaction is easily determined due to
the readily visible color change. When the yields are poor,
using pyridine instead of silica gel gives the correspond-
ing aldehydes with satisfactory yields.
5d
0.91 (t, 3 H, J = 6.9, CH3), 1.22–1.56 (m, 4 H, 2 CH2),
1.68–1.92 (m, 2 H, CH2CH2CHO), 2.02–2.31 (m, 4 H, 2
CH2C≡), 2.40–2.64 (m, 2 H, CH2CHO), 9.81 (t, 1 H,
J = 1.4, CHO)
5e
5f
1.92 (d, 3 H, J = 5.2, CH3), 6.06 (dd, 1 H, J = 7.9, 15.4,
CH=), 6.18–6.44 (m, 2 H, 2 CH=), 7.00–7.16 (m, 1 H,
CH=), 9.54 (d, 1 H, J = 7.9, CHO)
0.88 (t, 3 H, J = 6.5, CH3), 1.10–1.58 (m, 10 H, 5 CH2),
2.12–2.30 (m, 2 H, CH2CH=), 6.07 (dd, 1 H, J = 8.1,
15.1, CH=), 6.16–6.42 (m, 2 H, 2 CH=), 6.98–7.20 (m, 1
H, CH=), 9.54 (d, 1 H, J = 8.0, CHO)
4-Acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tet-
rafluoroborate (1a) was synthesized according to literature9,14,15 us-
ing nitroxyl radical 3 as a starting material.9,18,19 Oxidations 4 → 5
were performed using 1 mmol of starting alcohols (as described in
protocols below) except oxidation of 4f with 1a/silica gel (2 mmol)
and 4g, 4h, 4i, 4j with 1a/pyridine (0.5, 0.5, 3.14, 4.72 mmol, re-
spectively). All synthesized aldehydes 5a–k are known compounds,
5g
5h
5i
1.20–1.48 (m, 6 H, 3 CH2), 1.52–1.80 (m, 2 H,
CH2CH2CHO),1.73 (d, 3 H, J = 6.2, CH3CH=), 1.96–
2.12 (m, 2 H, CH2CH=), 2.42 (dt, 2 H, J = 1.8, 7.2,
CH2CHO), 5.40–6.12 (m, 4 H, CH=CHCH=CH), 9.76 (t,
1 H, J = 1.8, CHO)
1
and were obtained as oils (yields are given in Table 1, H NMR
spectra are presented in Table 2). Flash chromatography: silica gel
0.040–0.063 mm, 230–400 mesh (Merck 1.09385.1000), mobile
phase: hexane–EtOAc (10:1) (5b–h,j,k), hexane–EtOAc (30:1)
1.22–1.44 (m, 8 H, 4 CH2), 1.54–1.76 (m, 2 H,
CH2CH2CHO), 1.65 (d, 3 H, J = 6.2, CH3CH=), 1.94–
2.12 (m, 2 H, CH2CH=), 2.42 (dt, 2 H, J = 1.8, 7.2,
CH2CHO), 2.60–2.82 (m, 2 H, =CHCH2CH=), 5.28–
5.56 (m, 4 H, 2 CH=CH), 9.76 (t, 1 H, J = 1.8, CHO)
1
(5a), benzene–hexane–Et3N (1:1:0.006) (5i). H NMR [200 MHz,
CDCl3/TMS, d (ppm), J (Hz)] spectra were recorded using Varian
UNITYplus 200 apparatus.
Oxidation with 1a Using Silica Gel as a Catalyst; General Pro-
cedure
0.92 (t, 3 H, J = 7.4, CH3), 1.20–1.76 (m, 10 H, 5 CH2),
1.96–2.24 (m, 4 H, 2 CH2CH=), 2.43 (dt, 2 H, J = 1.9,
7.3, CH2CHO), 5.31 (dt, 1 H, J = 7.7, 10.7, CH=), 5.64
(dt, 1 H, J = 7.2, 14.8, CH=), 5.96 (br t, 1 H, J = 10.7,
CH=), 6.30 (ddq, 1 H, J = 1.5, 10.7, 14.8, CH=), 9.76 (t,
1 H, J = 1.9, CHO)
The starting alcohol 4 (1 mmol), 1a (340 mg, 1.1 mmol), silica gel
(230–400 mesh, 200 mg), and CH2Cl2 (8 mL) were placed in a flask
under argon. The slurry was magnetically stirred at r.t. and moni-
tored (TLC, silica gel, hexane–Et2O, 4:1, visualization: vanillin/
H2SO4) until no starting alcohol was observed [16–24 h:
4b,c,e,f,i,j,k, 48 h: 4a,d, 96 h: 4g,h (no 5g,h obtained)]. The mix-
ture was filtered through Celite (0.5 cm) and silica gel (230–400
mesh, 1 cm) and washed with CH2Cl2 (5 × 10 mL). The solvent was
evaporated under reduced pressure. The residue was isolated and
purified by flash chromatography.
5j
2.11 (distorted quint, 2 H, CH2CH2CH2), 2.68 (dt, 2 H,
J = 1.0, 6.9, CH2CHO), 3.60 (t, 2 H, J = 6.2, CH2Cl),
9.82 (t, 1 H, J = 1.0, CHO)
5k
1.22–1.96 (m, 8 H, 4 CH2), 2.30–2.52 (m, 2 H,
CH2CHO), 3.41 (t, 2 H, J = 6.7, CH2Br), 9.78 (t, 1 H,
J = 1.7, CHO)
Oxidation with 1a in Alkaline Medium in the Presence of Pyri-
dine; General Procedure
The starting alcohol 4 (1 mmol), 1a (624 mg, 2.08 mmol), anhyd
pyridine (166 mg, 170 mL, 2.1 mmol) and CH2Cl2 (10 mL) were
placed in a flask under argon. The slurry was magnetically stirred at
r.t. for 20–24 h, and then filtered. The filtrate was concentrated un-
monium salt in the absence or in the presence of pyridine
may be expressed in Scheme 2.
The actual mechanism for these oxidations was consid- der reduced pressure. The residue was triturated with Et2O (10 mL)
ered in detail in a recent paper,38 along with theoretical
and filtered through a funnel with a sintered disc and silica gel pad
(230–400 mesh, 2 cm). The silica gel was washed with Et2O (3 × 15
mL). The combined Et2O filtrates were concentrated under reduced
pressure. The residue was isolated and purified by flash chromatog-
raphy.
calculations that substantiate the many suggested mecha-
nisms for these reactions. A more detailed mechanistic
discussion will be presented in a forthcoming review.39
Synthesis 2007, No. 16, 2491–2494 © Thieme Stuttgart · New York