Stereochemical study on an oxygen-directed olefin oxidation and subsequent oxygen cyclization: Differences between peracid and metal oxide-catalyzed hydroperoxide in oxidation reactions

Article abstract of DOI:10.1016/j.tetasy.2013.05.025

Optically active (2S,4R)-2-hydroxy-4-pentyl enol ether was prepared for the first time and subjected to hydroxy-directed oxidations at the olefinic group. Treatment with m-chloroperbenzoic acid and tert-butyl hydroperoxide/vanadium acetylacetonate resulte

Full text of DOI:10.1016/j.tetasy.2013.05.025

Tetrahedron: Asymmetry 24 (2013) 833–837
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereochemical study on an oxygen-directed olefin oxidation and
subsequent oxygen cyclization: Differences between peracid and
metal oxide-catalyzed hydroperoxide in oxidation reactions
⇑
Aya Inoue, Tomonori Misaki, Morifumi Fujita, Tadashi Okuyama, Takashi Sugimura
Graduate School of Material Science, University of Hyogo, 3-2-1 Kohto, Kamigori, Ako-gun, Hyogo 678-1297, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 April 2013
Accepted 21 May 2013
Optically active (2S,4R)-2-hydroxy-4-pentyl enol ether was prepared for the first time and subjected to
hydroxy-directed oxidations at the olefinic group. Treatment with m-chloroperbenzoic acid and tert-
butyl hydroperoxide/vanadium acetylacetonate resulted in the same stereoface differentiation at the ole-
fin, with diastereomeric excesses as high as 79% and 92%, respectively, whereas the stereochemistry of
the products of subsequent nucleophilic additions of the hydroxy group was opposite.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
former reaction is classified as a substrate-controlled nucleophilic
addition, and is uncommon, while the latter is classified as a reac-
Electrophilic oxidation of an olefin can be directed to a certain
stereoface by a neighboring intramolecular hydroxy group.1,2
tion mechanism-controlled nucleophilic addition.4
A
The oxidation–cyclization sequence requires a remote and con-
formationally regulated hydroxy group to sufficiently direct the
initial oxidation and to promote an effective cyclization. A typical
example is the oxidation of (2R,4R)-2-hydroxy-4-pentyl enol
ethers, such as 1 (Scheme 2).5
The treatment of 1 with MCPBA gives quantitatively (7R)-2 with
up to 99% diastereomeric excess (de) (CH2Cl2, ꢀ78 °C), while the
oxidation of 1 with TBHP resulted in up to 97% de (40% yield with
Ti(OiPr)4 as a catalyst). The two different oxidants can be stereo-
controlled by a common directing effect, similar to the case of
the epoxidation of allylic alcohols, although the presence of an
typical example is the epoxidation of olefins, where an intramolec-
ular hydroxy group, mostly at the vicinal position, directs oxidants
to one face of the olefin, resulting in stereoselective epoxidation. As
the oxidant, both m-chloroperbenzoic acid (MCPBA) and tert-butyl
hydroperoxide (TBHP)/metal oxide catalyst are often employed.3
When the hydroxy group exists in an appropriate geometry to re-
act further with the oxidized olefinic carbon, a cyclic ether bond
can form in two different ways: addition from the same face as
the oxidation and addition from the opposite direction with War-
den inversion (Scheme 1, new C–O bonds are shown in red). The
HO
R1
O
b
HO
HO
R2
a
[O]
+
[O]
c
HO
R1
R2
R1
R2
R1
R2
O
a: Substrate controlled (hydroxyl directed) olefin oxidation
b: Substrate controlled SN1 like reaction to perform a syn-addition
c: Reaction mechanism controlled SN2 like reaction to perform an anti-addition
Scheme 1.
⇑
Corresponding author. Tel.: +81 791 58 0168.
E-mail address: sugimura@sci.u-hyogo.ac.jp (T. Sugimura).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.05.025

834
A. Inoue et al. / Tetrahedron: Asymmetry 24 (2013) 833–837
2. Results and discussion
2
4
O
O
O
OH
2.1. Preparation of 3
O
OH
7
HO [O]
Although 1 could be prepared in enantiomerically, diastereo-
merically, and chemically pure form on a large scale, it is fragile
and is especially unstable under acidic conditions. A racemic mix-
ture of 3 could be prepared by the isomerization of achiral meso-
2,4-pentanediol cyclohexanone acetal with Al(iBu)3; however, the
rac-3 produced was much less stable than 1, which necessitated
careful operation. When the Mitsunobu inversion of 1 was per-
formed to obtain the chiral ester analogue of 3, synthesis under
conventional conditions was not successful and only gave the ace-
tal (see Scheme 4). The Mitsunobu reaction is usually considered to
be a neutral reaction;8 however, in practice, the benzoic acid of the
initially employed pro-nucleophile could serve as a proton source
during the reaction. In order to reduce the acidity of the reaction
media, we used anisic acid in place of benzoic acid.9 Here the pres-
ence of trace (5%) amounts of pyridine in the reaction media was
also a key factor (it most likely protects the reactant from acidic
side products). With this modification, the anisic ester of 3 was ob-
tained in 63% yield after performing Al2O3 column chromatogra-
phy, with complete stereoinversion (Scheme 4). The higher
nucleophilicity, due to the stronger conjugate base of anisic acid
is an additional benefit.6 The basic hydrolysis reaction of the ester
obtained afforded stereochemically pure (2S,4R)-3 in 84% yield.
(7R)-2
si-re face oxidation to
give (7R)
(2R,4R)-1
mCPBA/-78 °C >99% de
TBHP/cat. up to 97% de
Scheme 2.
epoxy intermediate is not certain. Due to the symmetry of the chi-
ral tether (the 2,4-pentanediol moiety), the stereochemistry of the
cyclization step is unknown. The selectivity can be determined
with 3 containing a (2S,4R)-tether (Scheme 3). The oxidation of 3
is interesting in the initial oxidation step because it is unknown
whether the influences of the two stereogenic centers on the tether
for the oxidation work cooperatively or competitively.6
The stereocontrol ability of the (2S,4R) tether has been tested in
several different reactions; however, an enol ether-type substrate
such as 3 has not been investigated in an optically active form be-
cause the production of such a substrate is difficult. The selectivity
7
has been studied with racemic 3 prepared from the acetal of
meso-PD and cyclohexanone; however, the chiral information
was partially lost, and considering its synthetic value, when 3 is
used in a stereo-directing oxidation reaction, it must be enantio-
merically pure. Herein we reported a method for making optically
active 3 from 1 using a modified Mitsunobu reaction. The success-
ful preparation of this substrate would allow a comparison be-
tween (2R,4R)-1 and (2S,4R)-3 and thus determine the
stereocontrol ability of the tether. The stereochemistry of the ace-
tal forming steps is also reported.
2.2. Stereochemical assignment of 4–7
Racemic 310 was first prepared and treated with MCPBA at 0 °C.
The product was a stereoisomeric mixture obtained in 77% yield.
The isomeric ratio was endo/exo = 74:26, where the isolated minor
isomer was assigned as the exo isomer as deduced by NOE between
2H–7H and 4H–7H. Oxidation with another oxidant, [TBHP
2
4
O
O
O
O
O
OH
OH
OH
+
6
[O]
si-re face oxidation to
O
OH
give (7R)
(2R,4S,6R,7R)-4
(exo-isomer)
5
(2R,4S,6S,7R)-
(endo-isomer)
O
O
H
[O]
O
O
O
O
(2S,4R)-3
+
OH
OH
re-si face oxidation to
give (7S)
(2R,4S,6S,7S)-6
(endo-isomer)
(2R,4S,6R,7S)-7
(exo-isomer)
syn-addition
anti-addition
Scheme 3. Hydroxy-directing oxidation–cyclization with 3 containing the (2S,4R)-tether.
4
2
X
O
O
O
O
Mitsunobu
(2R,4R)-1
O
acetal
ester of (2S,4R)-3
X = H or MeO
Scheme 4.

A. Inoue et al. / Tetrahedron: Asymmetry 24 (2013) 833–837
835
(Ti(OiPr)4) molecular sieves 4 Å, 0 °C] primarily gave the acetal
(50%); however, the oxidized product obtained in low yield (21%)
was the exo-rich product, which suggests an unexpected reversal
in the stereochemistry between the oxidation reactions.
pounds, whereas H-7 was observed as four separate peaks at
isolated positions of d 5.00–5.05 for the endo-products 5 and 6
and at d 5.95–6.00 for the exo-products 4 and 7. From Mosher’s
method rule, H-8,80 of the (7R)-product should appear at a higher
field than that of the (7S)-product. Although H-8,80 was among
many unidentified peaks, the COSY spectrum provided the neces-
sary information, as shown in Figure 1 (y-axis). The stereochemis-
try determined by this method is identical to that obtained by
chemical correlation using 1,2-cyclohexanediol.
Next, we oxidized optically active (2S,4R)-3 with MCPBA or
TBHP/metal catalyst. According to the gas–liquid chromatographic
(GLC) analysis using a chiral column (b-DEX-325, 120 °C), all four
stereoisomers of 4–7 were observed as separate peaks, accompa-
nied by a peak corresponding to the cyclohexanone acetal of
meso-PD in some cases. The configuration at C7 was determined
by chemical correlation; that is, (R,R)-1,2-cyclohexanediol was
monoacetylated with Ac2O/pyridine/DMAP (23% yield) and oxi-
dized with PCC to give (2R)-2-acetoxycycohexanone (79%). Acetal
formation with meso-2,4-pentanediol in the presence of PyꢁTsOH
at benzene reflux resulted in 49% yield, and the subsequent basic
hydrolysis should give the (7R)-product; GLC analysis was used
to identify the product as endo-acetal 5. The corresponding exo-iso-
mer was also produced as exo-(7R)-acetal 4 (4:5 = 1:15.7). From
these results, the other enantiomer of the endo-(2S)-product was
assigned as 6; 7 should represent the exo-(2S)-product.
2.3. Stereoselectivity in the oxidation of (2S,4R)-3
The isomeric ratios of 4–7 obtained by the oxidation of (2S,4R)-
3 were determined by GLC analysis;12 the results are summarized
in Table 1. The major isomer produced by the MCPBA oxidation in
dichloromethane was (7R)-endo-5. The calculated (7R)-selectivity
versus (7S) was 52% de at room temperature, which increased to
70% de at ꢀ78 °C (entries 1–3). The acetal formation step was
mainly via an anti addition in the (7R)-product, whereas the minor
(7S)-product showed a high syn-selectivity. The presence of a weak
inorganic base did not affect the selectivity (entry 4),13 whereas a
less-directed reaction in polar THF resulted in anti-cyclization
and poor 7-selectivity. Overall, the MCPBA oxidation is less stereo-
selective with 3 (70% de at ꢀ78 °C) than with 1 (99% de at ꢀ78 °C),
while a syn-cyclization preference resulted in an endo-rich product.
The TBHP oxidation of (2S,4R)-3 with Ti(Oi-Pr)4 in dichloro-
methane also gave a (7R)-rich product in 56% enantiomeric excess
(ee), but differed from the peracid oxidation, where the syn-cycli-
zation of the (7R)-product to give exo-4 was predominant (entry
6). The low face-selectivity was a disappointing issue, and poor
selectivity was also found with the Mo(CO)6-catalyzed reaction
(entry 7). However, the selectivity of the vanadium acetylacetonate
(VO(acac)2)-catalyzed reaction was not poor, and the reaction in
toluene at ꢀ20 °C gave the best results with 92% de and 18/1
syn-cyclization selectivity (entry 10, 93% exo, 94.8% ee). The exo-
(7R)-selectivity with TBHP is clearly attributable to syn-cyclization.
The observed stereoselectivity at C7 is higher than the oxidation of
1 with the same catalyst (87% de).
In order to confirm the above assignments, additional experi-
ments with Mosher’s ester were performed.11 A small amount of
the reaction mixture was treated with (R)-MTPACl to give the
(S)-MTPA esters of 4–7. The 1H NMR spectra of the reaction mix-
ture indicated the presence of impurities and decomposed com-
Nucleophilic addition to an epoxide usually occurs through an
SN2 mechanism.14 The anti-selectivity with MCPBA oxidation
may indicate the formation of an epoxide intermediate, whereas
the TBHP oxidation tends to induce cyclization, which interrupts
the epoxide formation process. The generality of these tendencies
was confirmed with cycloheptanone derivative 9.15 The Mitsunobu
reaction of 8 to 9 was not as smooth as that of 1 to 3, and a mixture
of 9 and cycloheptanone acetal was obtained. Compound 9 did not
exceed 50% of the contents, and could not be isolated. The oxida-
tion of the mixture gave four peaks, which were temporarily as-
signed to be 40–70 the same as 4–7 as shown in Table 2. As
Fig. 1. COSY spectrum of the (S)-MTPA ester of rac-4.
Table 1
Yields and isomeric compositions in the oxidation of 3 under various conditions
Entry
Conditions (reagent/(catalyst)/solvent/temp)
Yielda
Composition of the four isomers/%
(7R)/(7S)
syn versus anti additions
(7R)-Product (4/5) (7S)-Product (6/7)
4
5
6
7
1
2
3
4
5
6
7
8
9
10
MCPBA/CH2Cl2/22 °C
MCPBA/CH2Cl2/0 °C
100
93
100
87
99
89
53
100
93
24
21
21
23
14
63
45
76
87
91
52
56
64
54
24
15
20
19
7.3
5.1
22
18
13
19
22
16
17
3.8
3.0
2.2
2.3
4.7
1.7
3.9
40
6.3
18
1.5
2.7
1.9
76/24
77/23
85/15
77/23
38/62
78/22
65/35
95/5
1/2.2
1/2.7
1/3.1
1/2.4
1/1.7
4.2/1
2.3/1
4/1
9.6/1
3.8/1
7.6/1
4.9/1
1/1.8
2.5/1
1/1.1
2.5/1
1.1/1
1.2/1
MCPBA/CH2Cl2/ꢀ76 °C
MCPBA/CH2Cl2+NaHCO3 aq/0 °C
MCPBA/THF/0 °C
TBHP/Ti(Oi-Pr)4/CH2Cl2/0 °C
TBHP/Mo(CO)6/CH2Cl2/0 °C
TBHP/VO(acac)2/CH2Cl2/0 °C
TBHP/VO(acac)2/toluene/0 °C
TBHP/VO(acac)2/toluene/ꢀ20 °C
94/5
96/4
12/1
18/1
100
a
The yields of 4–7 were determined by GLC analysis. Most of the side product was the unoxidized cyclohexanone acetal of PD.

836
A. Inoue et al. / Tetrahedron: Asymmetry 24 (2013) 833–837
Table 2
Yields and isomeric compositions in the oxidation of 9 under various conditions
Entry
Conditions (reagent/(catalyst)/solvent/temp)
Yielda
Composition of four isomers/%
(7R)/(7S)
Syn versus anti additions
40
50
60
70
(7R-product (40/50)
(7S)-product (60/70)
1
2
3
MCPBA/CH2Cl2/ꢀ76 °C
MCPBA/CH2Cl2/0 °C
TBHP/VO(acac)2/CH2Cl2/0 °C
—
—
—
44
51
77
39
26
19
14
17
2.8
2.8
6.3
1.3
83/17
77/23
95/5
1.1/1
1.9/1
3.9/1
4.9/1
2.7/1
2.5/1
O
OH
O
OH
O
O
[O]
+
4'
+
5'
+
6'
+
7'
acetal
(2S,4R)-9
(2R,4R)-8
Scheme 5. Hydroxy-directing oxidation–cyclization with 9 containing the (2S,4R) tether.
expected, compounds 3 and 9 showed little difference in the selec-
tive oxidations to give (7S). In the case of the MCPBA oxidation, 9
gave the thermodynamically stable endo-product more than 3. In
the case of TBHP/VO(acac)2 oxidation, 9 gave the four products
with the same (Scheme 5) selectivity as 3 (Table 1, entry 8).
J = 8.2 Hz, 4.1 Hz), 2.20 (1H,br), 1.80 (1H, m), 1.65–1.50 (3H,
m),1.49 (2H, dt, J = 13.1 Hz, 2.6 Hz), 1.44 (1H, m), 1.39 (1H, m),
1.28 (1H, m), 1.16 (3H, d, J = 6.2 Hz), 1.15 (3H, d, J = 6.2 Hz), 1.13
(1H, m); 13C NMR (150 MHz, CDCl3): d 98.98, 73.99, 65.83, 64.58,
40.66, 30.88, 29.53, 26.46, 25.75, 22.13, 15.24; IR (neat): 3479,
2932, 2663, 1722, 1446, 1382, 1233, 1042, 1011, 949, 920, 856,
825, 795, 754, 704, 678 cmꢀ1
; HRMS (ESI-TOF) calcd for
3. Conclusion
C
11H20NaO3 [M+Na]+: 223.131, found: 223.131. exo-product 4/7:
colorless oil; 1H NMR (600 MHz, CDCl3): d 4.48 (1H, m), 4.06 (1H,
m), 4.00 (1H, m), 2.15 (1H, s), 1.81 (1H, m), 1.75 (1H, m), 1.56–
1.48 (8H, m), 1.19 (3H, d, J = 6.2 Hz), 1.14 (3H, d, J = 6.2 Hz); 13C
NMR (150 MHz, CDCl3): d 98.74, 64.91, 64.33, 62.70, 39.81, 33.65,
27.98, 22.01, 21.99, 21.69, 18.69; IR (neat): 3466, 2936, 1713,
A Mitsunobu inversion reaction for acid-sensitive compounds
was developed. Using this reaction, we prepared optically active
3. In order to assign the configuration of the secondary alcohol
with a complex NMR spectrum, the Mosher’s ester rule was used
in conjunction with 2D COSY spectra. The best oxidant dealing
with the stereoface selectivity between (2R,4R)-1 and (2S,4R)-3 dif-
fered: MCPBA was the best oxidant for 1, whereas TBHP was the
best oxidant for 3. The syn/anti-cyclization selectivity with 3 was
found to be opposite between the oxidants. Herein we have re-
ported on our attempts to clarify the stereochemistry of the oxida-
tion–cyclization process with the chiral PD-tethered reactions.
1446, 1382, 1238, 1175, 1116, 1081, 1041, 1011, 894, 856 cmꢀ1
;
HRMS (ESI-TOF) calcd for C11H20NaO3 [M+Na]+: 223.131, found:
223.131.
4.3. (2S,4R)-4-(Cyclohex-1-en-1-yloxy)pentan-2-yl 4-
methoxybenzoate (ester of 3)
A solution of DIAD (103 mg, 0.51 mol) in THF (3.0 ml) was
added dropwise over a period of 2 min to a stirred solution of
4. Experimental
4.1. General
(2R,4R)-4-(cyclohex-1-en-1-yloxy)pentan-2-ol
1
(98.0 mg,
0.53 mmol), p-anisic acid (79.3 mg, 0.52 mmol), PPh3 (143.3 mg,
0.55 mmol), and a few drops of pyridine in THF (1.0 ml) at room
temperature. After being stirred for 4 h, the reaction mixture was
concentrated and purified by Al2O3 column chromatography (hex-
ane/EtOAc = 6:1) to give the ester of 3 (106.2 mg, 0.33 mmol, 63%
yield).
NMR spectra were recorded on a JEOL JNM-ECA600 spectrome-
ter operating at 600 MHz for 1H NMR and at 150 MHz for 13C NMR.
The chemical shifts (d ppm) for the 1H NMR spectra of samples dis-
solved in CDCl3 are downfield from TMS (=0). In the 13C NMR spec-
tra, the chemical shifts are reported on a scale relative to CDCl3
(77.0 ppm), which was used as an internal reference. IR spectra
were recorded on a JASCO FT/IR-410 spectrophotometer. Optical
rotations were measured on a Perkin Elmer 241 polarimeter. ESI
mass spectra were recorded on a JEOL JMS-T100LC spectrometer.
Colorless oil; 1H NMR (600 MHz, CDCl3):
d 7.99 (2H, d,
J = 8.9 Hz), 6.89 (2H, d, J = 8.9 Hz), 5.22 (1H, m), 4.62 (1H, t,
J = 3.8 Hz), 4.18 (1H, m), 3.83 (3H, s), 2.19 (1H, m), 2.01–2.00
(2H, m), 1.97–1.95 (2H, m),1.67–1.50 (3H, m), 1.49 (2H, dt,
J = 8.9 Hz, 5.3 Hz), 1.33 (3H, d, J = 6.2 Hz), 1.22 (3H, d, J = 6.2 Hz);
13C NMR (150 MHz, CDCl3): d 165.53, 163.05, 152.36, 131.30,
122.98, 113.38, 113.32, 94.81, 68.61, 67.70, 55.17, 42.27, 29.94,
26.77, 23.36, 22.74, 22.53, 20.32, 19.49; IR (neat): 3403, 2928,
2042, 1917, 1714, 1606, 1512, 1455, 1256, 848, 770, 696, 664,
4.2. Oxidation of (2R⁄,4S⁄)-3 with MCPBA to give racemic endo-5/
6 and exo-4/7
To a solution of rac-3 (192.4 mg, 1.04 mmol) in dichlorometh-
ane (5 ml), MCPBA (210.6 mg, 1.22 mmol) was added at 0 °C with
stirring. After 10 min, the mixture was allowed to warm to room
temperature and was stirred for 5 h. The reaction mixture was ex-
tracted and purified by silica gel column chromatography (5 g, elu-
tion with 20% ethyl acetate in hexane) to give an endo/exo mixture
(161 mg, 77.4%). The mixture was further purified to give partially
613 cmꢀ1; ½a 2D0
¼ þ23:0 (c 1.02, CH2Cl2); HRMS (ESI-TOF) calcd
ꢂ
for C19H26NaO4 [M+Na]+: 341.173, found: 341.173.
4.4. (2S,4R)-4-(Cyclohex-1-en-1-yloxy)pentan-2-ol 3
A 1.0 M NaOH aqueous solution (300 ll) was added dropwise to
a stirred solution of (2S,4R)-4-(cyclohex-1-en-1-yloxy)pentan-2-yl
4-methoxybenzoate (ester of 3) (51.1 mg, 0.16 mmol) in MeOH
separated 5/6 and 4/7. Racemic endo-product 5/6: colorless oil; 1
NMR (600 MHz, CDCl3): d 4.04–3.90 (2H, m), 3.44 (1H, dd,
H

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837
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(1.0 ml) at room temperature. After being stirred at 65 °C until the
substrate could not be detected by silica gel TLC analysis, the reac-
tion mixture was cooled to room temperature. The mixture was ex-
tracted four times with CH2Cl2, and the combined organic phase
was washed with H2O and dried (K2CO3). After 10 drops of Et3N
were added, the solution was concentrated and purified by Al2O3
column chromatography (hexane/EtOAc = 4:1) to give the product
3 (24.6 mg, 0.13 mmol, 84% yield). Colorless oil; 1H NMR (600 MHz,
CDCl3): d 4.70 (1H, t, J = 4.1 Hz), 4.25 (1H, m), 3.94 (1H, m), 2.92
(1H, s), 2.04–2.01 (2H, m), 2.00–1.98 (2H, m), 1.74 (1H, dt,
J = 17.2 Hz, 7.2 Hz), 1.63 (2H, m), 1.57 (1H, dt, J = 14.2 Hz, 3.1 Hz),
1.52–1.49 (2H, m), 1.19 (3H, d, J = 6.2 Hz), 1.16 (3H, d, J = 6.2 Hz);
13C NMR (150 MHz, CDCl3): d 152.17, 96.65, 71.57, 67.28, 64.20,
45.59, 28.28, 23.64, 23.01, 22.73, 19.93; IR (neat) 3389, 2929,
1664, 1446, 1374, 1334, 1267, 1183, 1041, 1007, 918, 828,
769 cmꢀ1; ½a 2D0
¼ þ51:0 (c 0.52, CH2Cl2); HRMS (ESI-TOF) calcd
ꢂ
for C11H20NaO2 [M+Na]+: 207.136, found: 207.153.
4.5. Oxidations of (2S,4R)-9
8. Hughes, D. L. In Organic Reaction; Paquette, L. A., Ed.; Wiley: New York, 1992;
Vol. 42, pp 335–659.
9. pKa = 4.20 for benzoic acid and 4.47 for anisic acid (in H2O).
10. Sugimura, T.; Tei, T.; Mori, A.; Okuyama, T.; Tai, A. J. Am. Chem. Soc. 2000, 122,
2128.
11. Sullivan, G. R.; Dale, J. A.; Mosher, H. S. J. Org. Chem. 1973, 38, 2143.
12. Stereoisomerization of the products was not observed under the reaction
conditions used herein.
13. Stereochemical inertness for a base is important. In the presence of NaHCO3, an
accidentally contaminated or produced acid can be trapped in the reaction
media.
Compound (2R,4R)-8 was prepared from the cycloheptanone
acetal as reported, and then converted into (2S,4R)-9 by the same
procedure for 1–3 (85–90% crude yield). The mixture of 9 and
the acetal was oxidized as above, and analyzed by a GLC (b-
DEX325, 120 °C, 25 cm/s) to give four peaks at 26.5, 26.9, 27.2,
and 27.7 min (by the same conditions, the oxidation mixture of 3
gave peaks at 27.2 min for 4, 27.8 min for 7, 28.6 min for 6, and
29.4 min for 5).
14. Hanson, R. N. In Organic Reactions; Wiley: Hobken, 2002; 60, pp 1–156.
15. At this stage, the present oxidation has limited applicability, and the
cyclopentanone derivative was not successful.
References
1. Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307.