TiCl4/tert-butyl hydroperoxide: Chemioselective oxidation of secondary alcohols and suppression of sharpless epoxidation

Article abstract of DOI:10.1055/s-2008-1066997

Replacing Ti(Oi-Pr)₄ with TiCl₄ under the normal Sharpless epoxiation conditions resulted in a shut down of the epoxidation reaction. Instead, a chemioselective oxidation of secondary alcohols in the presence of primary alcohols occurred. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1066997

LETTER
1021
TiCl4/tert-Butyl Hydroperoxide: Chemioselective Oxidation of Secondary
Alcohols and Suppression of Sharpless Epoxidation
Selective
Oxidati
h
on of Second
u
a
ry
A
lcohol
n
s
-Tin Shei, Hao-Lun Chien, Kuangsen Sung*
Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan
Fax +886(6)2740552; E-mail: kssung@mail.ncku.edu.tw
Received 25 December 2007
reported to carry out selective oxidation of secondary al-
cohols in the presence of LaCoO3,5n HBr,5o CuCl2/
Abstract: Replacing Ti(Oi-Pr)4 with TiCl4 under the normal Sharp-
less epoxiation conditions resulted in a shut down of the epoxida-
tion reaction. Instead, a chemioselective oxidation of secondary
alcohols in the presence of primary alcohols occurred.
BQC,5p,q
zeolites,5h
[PhCH2NMe3][Mo(O)Br4],5j
[C5H5N+(CH2)15Me]3[PMo12O40],3–5i
Cu(acac)2,5d
Cr/PILC,5g
or
VO(acac),5k
Zr(On-Pr)4,5f
Key words: epoxidation, selective oxidation, alcohol
[Cn*RuIII(CF3CO2)3·H2O]5e catalysts. To the best of our
knowledge, selective oxidation of secondary alcohols by
TiCl4/TBHP is still unknown.
The Sharpless epoxidation is a well-known reaction,
which realizes kinetic resolution of allyl alcohols by ste-
reoselective oxidation of allyl alcohols to the correspond-
ing epoxides with the alcohol functionality remaining
intact.1,2 The reaction uses a combination of Ti(Oi-Pr)4,
tert-butyl hydroperoxide (TBHP), and a chiral ligand,
which may either be ( )-diisopropyl tartrate (DIPT) or
( )-diethyl tartrate (DET). For Sharpless epoxidations,
use of one equivalent of DIPT per Ti speeds up the epoxi-
dation reactions, while use of less than or more than one
equivalent of DIPT per Ti results in a rate retardation of
the epoxidation.1a Hence, the functions of DIPT in the
Sharpless epoxidation are both rate and stereoselective
control. Without DIPT, allylic alcohols can still be oxi-
dized to the corresponding epoxides by Ti(Oi-Pr)4/
TBHP.1a
Recently, when we did Sharpless epoxidation by replac-
ing (+)-DIPT with another chiral ligand, we accidentally
found a ketone byproduct. This triggered us to explore the
oxidation of alcohols and allyl alcohols by using Ti com-
plex and TBHP. In this paper, we found it most surprising
and interesting that substituting TiCl4 with Ti(Oi-Pr)4 un-
der conditions that are otherwise very similar to those
used in Sharpless epoxidation, ‘shut down’ the epoxida-
tion and instead achieved selective oxidation of secondary
alcohols in the presence of primary alcohols. In addition,
in order to shed light on the suppression of Sharpless ep-
oxidation, functional-group reactivity of the olefin, the
secondary alcohol, and the primary alcohol to the catalyst
TiCl4 or Ti(Oi-Pr)4 in the presence of TBHP were also ex-
amined.
In order to carry out the oxidation with TiCl4/TBHP in a
less polar solvent, anhydrous TBHP (0.1:1.7) must be
used. The anhydrous TBHP was prepared by azeotropic
distillation of 70% aqueous TBHP with toluene.6 Various
alcohols 1a–n were tested using this oxidation method
and the results7 are shown in Table 1.
It was reported that replacement of Ti(Oi-Pr)4 with Ti(Oi-
Pr)2Cl2 in Sharpless epoxidation inverted the reaction
enantioselectivity. For instance, use of Ti(Oi-Pr)2Cl2/(+)-
DET/TBHP (2:1:2 ) oxidized allyl alcohols to the corre-
sponding chloro alcohols by way of a regiospecific open-
ing of intermediate epoxides, whose enantioselectivity
was opposite to that of epoxides produced by Ti(Oi-Pr)4/
(+)-DET/TBHP (2:2:2).3a When Ti(Oi-Pr)4 was replaced
by TiCl4 in Sharpless epoxidation, even non-functional-
ized olefins could be epoxidized. For example, use of
TiCl4/TBHP (1.2:1.2) could effect the chlorohydroxyla-
tion of olefins, including non-functionalized ones, via in-
termediate epoxides.3b
When the primary allyl alcohol 1a was subjected to the
oxidation conditions in the presence of TiCl4/TBHP
(0.1:1.7) under a refluxing condition for 2 days, no reac-
tion occurred and neither epoxide nor aldehyde could be
detected. However, reaction of the secondary allyl alcohol
1b with TiCl4/TBHP (0.1:1.7) under a refluxing condition
for 2 days generated the corresponding ketone 2b as the
only product in 60% yield, together with 40% of unreact-
ed 1b. Both of the reactions did not generate any epoxide,
indicating that Sharpless epoxidation was suppressed in
the oxidation with TiCl4/TBHP (0.1:1.7). Based on the re-
sults of the preceding two reactions, the functional-group
reactivity to the reagent of TiCl4/TBHP can be understood
as follows: secondary alcohol >> primary alcohol or ole-
fin of allyl alcohol. The same reagent of TiCl4/TBHP has
also been used by Sharpless et al. As shown in Scheme 1,
chlorohydroxylation of the allyl ether 5 was carried out by
TiCl4/TBHP (1.2:1.2) in 2 hours and produced the chloro
Functional-group transformation from alcohols to carbon-
yl groups is one of the most important issues in organic
chemistry.4 Oxidants which show good selectivity be-
tween primary and secondary alcohols are valuable, and
they include halogen-based oxidants, peroxides in the
presence of transition-metal complexes, dioxiranes, and
Oppenauer oxidation variations.5 Among them, TBHP is
SYNLETT 2008, No. 7, pp 1021–1026
x
x.
x
x.
2
0
0
8
Advanced online publication: 17.03.2008
DOI: 10.1055/s-2008-1066997; Art ID: W22207ST
© Georg Thieme Verlag Stuttgart · New York

1022
C.-T. Shei et al.
LETTER
Replacement of TiCl4 with Ti(Oi-Pr)4 in the oxidation of
the allyl alcohols gave in the following results. When the
primary allyl alcohol 1a reacted with Ti(Oi-Pr)4/TBHP
(1:2) at –20 °C for 1 day, the corresponding a-hydroxyl
epoxide 3a was produced in 85% yield without any de-
tectable aldehyde product. This is consistent with Sharp-
less’ results.1 When the secondary allyl alcohol 1b was
treated with Ti(Oi-Pr)4/TBHP (0.1:1.7) at –20 °C for 4
hours, the corresponding epoxide 3b and ketone 2b were
generated in 23 and 16% yields, respectively, leaving
around 61% unreacted 1b. According to the results of the
preceding two reactions, the sequence of functional-group
reactivity to the reagent of Ti(Oi-Pr)4/TBHP can be under-
stood as follows: olefin of allyl alcohol > secondary alco-
hol >> primary alcohol.
Cl
TiCl4 (1.2 equiv)
TBHP (1.2 equiv)
n-C7H15
OMe
n-C7H15
OMe
CH2Cl2, –78 °C
OH
6 92%
5
Scheme 1
alcohol 6 in 92% yield by way of the intermediate ep-
oxide.3b In this reaction, it was reported that at least 1.2
equivalents of TiCl4 were needed to functionalize the ole-
fin at –78 °C. It indicated that excess amount of TiCl4 was
needed to functionalize an olefin functional group, and
that was consistent with what we found.
Table 1 The TiCl4- or Ti(Oi-Pr)4-Catalyzed Selective Oxidation of Secondary Alcohols with TBHP in Chloroform
Substrate
Reagent
Temp
Time
Product (yield)
O
O
OH
OH
O
O
OH
OH
0.1:1.7
TiCl4/TBHP
Reflux
2 d
1a
2a (Trace)
3a (Trace)
3a (85%)
3b (Trace)
3b (23%)
1:2
–20 °C
Reflux
1 d
2 d
Ti(Oi-Pr)4/TBHP
1a
1b
2a (Trace)
2b (60%)
O
O
0.1:1.7
TiCl4/TBHP
O
O
OH
OH
OH
OH
0.1:1.7
Ti(Oi-Pr)4/TBHP
–20 °C
Reflux
Reflux
4 h
2 d
2 d
1b
2b (16%)
O
OH
0.1: 1.7
TiCl4/TBHP
1c
2c (80%)
O
OH
0.1:1.7
TiCl4/TBHP
1d
2d (85%)
OH
O
0.1:1.7
TiCl4/TBHP
r.t.
1 d
2e (81%)
1e
OH
O
0.1:1.7
Ti(Oi-Pr)4/TBHP
r.t.
1 d
2 d
2e (58%)
1e
1f
0.1:1.7
TiCl4/TBHP
Reflux
OH
O
2f (Trace)
Synlett 2008, No. 7, 1021–1026 © Thieme Stuttgart · New York

LETTER
Selective Oxidation of Secondary Alcohols
1023
Table 1 The TiCl4- or Ti(Oi-Pr)4-Catalyzed Selective Oxidation of Secondary Alcohols with TBHP in Chloroform (continued)
Substrate
Reagent
Temp
Time
1 d
Product (yield)
OH
O
OH
OH
0.1:1.7
TiCl4/TBHP
Reflux
O
O
1g
2g (90%)
OH
O
0.1:1.7
TiCl4/TBHP
r.t.
0.5 h
O
O
O
1h
1i
2h (>99%)
OH
O
OEt
OEt
0.1:1.7
Reflux
1 d
TiCl4/TBHPa
O
2i (72%)
OH
O
NHn-Bu
NHn-Bu
0.1:1.7
TiCl4/TBHP
Reflux
Reflux
2 d
2 d
O
O
1j
2j (85%)
O
O
OH
0.1: 1.7
TiCl4/TBHP
OH
OH
O
1k
1l
2k (50%)
4k (Trace)
OH OH
O
OH
O
O
0.1: 1.7
TiCl4/TBHP
Reflux
Reflux
2 d
2 d
2l (90%)
O
4l (Trace)
O
OH
OH
0.1:1.7
TiCl4/TBHP
O
OH
1m
2m (Trace)
4m (Trace)
OH
O
O
0.1:1.7
TiCl4/TBHP
Reflux
2 d
OH
OH
O
1n
a Solvent: CH2Cl2.
2n (Trace)
4n (Trace)
Similar reagent of Ti(Oi-Pr)2Cl2/TBHP (2:2) has also By comparing Scheme 1 and Scheme 2 with the oxidation
been used by Sharpless et al. to realize chlorohydroxyla- of 1a or 1b by TiCl4/TBHP (0.1:1.7), it indicates that more
tion of the primary allyl alcohol 7, forming the corre- than stoichiometric amount of TiCl4 is needed to function-
sponding chloro diols 8 in 4 hours through the intermedate alize the olefin functional group, which is what Sharpless
epoxide3a (Scheme 2). In this reaction, 2 equivalents of reported.3b In addition, according to the oxidation of 1a or
Ti(Oi-Pr)2Cl2 were used and the reaction temperature was 1b by TiCl4/TBHP (0.1:1.7), the sequence of functional-
kept at 0 °C. It was reported that excess amount of Ti(Oi- group reactivity to the reagent of TiCl4/TBHP (0.1:1.7) is:
Pr)2Cl2 was needed to functionalize the olefin in secondary alcohol >> primary alcohol or olefin of allyl al-
Scheme 2.
cohol. The preceding two key points may shed light on the
suppression of Sharpless epoxidation. On the other hand,
because the sequence of functional-group reactivity to the
reagent of Ti(Oi-Pr)4/TBHP is: olefin of allyl alcohol >
secondary alcohol >> primary alcohol; so the catalyst
Ti(Oi-Pr)4 is a good choice for Sharpless epoxidation.
TiCl2(Oi-Pr)2 (2 equiv)
TBHP (2 equiv)
(+)-DET (1 equiv)
Cl
OH
OH
OH
n-C14H29
Oxidation of the secondary alcohols 1c–e with alkyl or
aryl substituents by TiCl4/TBHP (0.1:1.7) at reflux or
room-temperature conditions generated the correspond-
ing ketones 2c–e in good yields. These reactions were
n-C14H29
CH2Cl2, –78 °C
7
8 76%
Scheme 2
Synlett 2008, No. 7, 1021–1026 © Thieme Stuttgart · New York

1024
C.-T. Shei et al.
LETTER
usually incomplete with some unreacted reactants, but did not reduce yields of the oxidation of the secondary al-
they produced very little byproducts. Conversely, oxida- cohols. The reactions were usually incomplete with little
tion of the primary alcohol 1f with TiCl4/TBHP (0.1:1.7) byproducts. In addition, the vicinal carboxylic acid group
at reflux conditions was too slow to detect any oxidation in 1g increased the yield of the oxidation and the vicinal
product 2f in 2 days. The preceding results indicate that ketone group in 1h dramatically increased both oxidation
use of TiCl4/TBHP (0.1:1.7) is capable of selectively oxi- rate and yield with an excellent yield (>99%) in half an
dizing secondary alcohols. These results are better than hour. These results are similar to those carried out by
those done by TBHP, zeolites, and microwave, but are TBHP in the presence of Cu(acac)2 catalyst.5d
similar to those carried out by TBHP in the presence of
Is oxidation of a primary allyl alcohol with TiCl4/TBHP
(0.1:1.7) similar to that of other primary alcohols? When
the primary allyl alcohol 1a was subjected to the oxidation
with TiCl4/TBHP (0.1:1.7) at –20 °C or a reflux condition
for 2 days, no reaction occurred. However, when the sec-
ondary allyl alcohol 1b was treated with TiCl4/TBHP
[PhCH2NMe3][Mo(O)Br4],5j
[C5H5N+(CH2)15Me]3[PMo12O40],3–5i
Cu(acac)2,5d
VO(acac),5k Zr(On-Pr)4,5f Cr–PILC,5g LaCoO3,5n HBr,5o
CuCl2/BQC,5p,q or [Cn*Ru(III) (CF3CO2)3·H2O]5e cata-
lysts.
Is the selective oxidation applied to molecules carrying (0.1:1.7) at reflux conditions, the corresponding ketone 2b
both primary and secondary alcohols? When the 1,3-diol was the only product with 60% yield, leaving around 40%
1k carrying both primary and secondary alcohols was sub- unreacted 1b. These results are completely different from
jected to the oxidation with TiCl4/TBHP (0.1:1.7), the b- those carried out by TBHP, zeolites, and microwave,5h
hydroxy ketone 2k was produced, where the secondary al- where epoxidation of allyl alcohols occurs, and those
cohol group was converted into the ketone group and the done
by
TBHP
in
the
presence
of
primary alcohol remained intact. The fair yield was [Cn*Ru(III)(CF3CO2)3·H2O],5e where primary allyl alco-
caused by incomplete reaction with around 50% unreact- hols are oxidized to the corresponding a,b-unsaturated al-
ed 1k. It seems that oxidation of the secondary alcohol has dehydes.
been slightly interfered with the primary b-OH, causing a
What if the catalyst TiCl4 is replaced by Ti(Oi-Pr)4 for the
reduced yield. When another type of 1,3-diol 1l with two
selective oxidation? When the secondary alcohol 1e was
secondary alcohol functional groups was subjected to the
oxidation with TiCl4/TBHP (0.1:1.7), the b-hydroxy ke-
treated with TiCl4/TBHP (0.1:1.7) or Ti(Oi-Pr)4/TBHP
(0.1:1.7) at room temperature for one day, the correspond-
tone 2l was generated in a good yield of 90%. It seems that
ing ketone 2e was produced in 81 and 58% yield, respec-
the secondary b-OH group slightly increases the oxidation
tively. It indicates that Ti(Oi-Pr)4/TBHP (0.1:1.7) carries
yield. However, when the amount of the oxidizing reagent
out oxidation of the seconday alcohol slower than TiCl4/
was doubled, the yield of the ketone 2l increased while the
TBHP (0.1:1.7).
diketone 4l could not be detected. The preceding results
In summary, the oxidation with TiCl4/TBHP (0.1:1.7) un-
indicate that the oxidation with TiCl4/TBHP (0.1:1.7) se-
der conditions that are otherwise very similar to those
lectively oxidizes the secondary alcohol in the presence of
used in Sharpless epoxidation surprisingly ‘shut down’
the primary alcohol. These results are similar to those car-
the epoxidation and instead afforded selective oxidation
ried out by TBHP in the presence of
of secondary alcohols in the presence of primary alcohols.
Two key points may shed light on the suppression of
Sharpless epoxidation. Firstly, the sequence of the func-
tional-group reactivity to the reagent of TiCl4/TBHP
(0.1:1.7) is: secondary alcohol >> primary alcohol or ole-
fin of allyl alcohol. Secondly, excess amount of TiCl4 is
needed to functionalize the olefin functional group. The
sequence of the functional-group reactivity to the reagent
of Ti(Oi-Pr)4/TBHP is: olefin of allyl alcohol > secondary
alcohol >> primary alcohol. As a result, the catalyst
Ti(Oi-Pr)4 is a good choice for Sharpless epoxidation. Use
of TiCl4/TBHP (0.1:1.7) realized selective oxidation of
the secondary alcohol in the presence of the primary alco-
hol. In the oxidation of the secondary alcohol with TiCl4/
TBHP (0.1:1.7), the b-hydroxyl group did not suppress it
but the a-hydroxyl group did. Adjacent functional groups,
[C5H5N+(CH2)15Me]3[PMo12O40],3–5i VO(acac),5k HBr,5o
and Zr(On-Pr)4 catalysts.5f
On the other hand, when the 1,2-diols 1m,n bearing pri-
mary or secondary alcohols were subjected to the oxida-
tion with TiCl4/TBHP (0.1:1.7), no reaction occurred and
the corresponding ketones 2m,n were not detectable.
These results are completely different from those carried
out by TBHP/Cr/PILC,5g or HBr,5o where selective oxida-
tion of secondary alcohols occurs, and from those done by
TBHP/[C5H5N+(CH2)15Me]3[PMo12O40],3–5i periodate,4
and Dess–Martin periodinane,8 where cleavage of C–C
bond occurs. In addition, in comparison with the results
for the oxidation of 1n and 1m, the result for the selective
oxidation of 1,3-diol 1k with TiCl4/TBHP (0.1:1.7) is ex-
cellent.
Is the oxidation of the secondary alcohol with TiCl4/ such as ketone, carboxylic acid, ester, and amide, did not
TBHP (0.1:1.7) inhibited by other functional groups suppress the TiCl4-catalyzed oxidation of the secondary
which are adjacent to it? When the secondary alcohols alcohol. Further investigation of the mechanism of this
1g–j with other functional groups at Ca such as ketone, oxidation is under way by kinetic and computational stud-
carboxylic acid, ester, or amide were subjected to the ox- ies.
idation with 0.1:1.7 TiCl4–TBHP, these functional groups
Synlett 2008, No. 7, 1021–1026 © Thieme Stuttgart · New York

LETTER
Selective Oxidation of Secondary Alcohols
1025
by trap-to-trap fractionation and other products were
purified by column chromatography with silica gel as
Acknowledgment
Financial support from the National Science Council of Taiwan
(NSC 95-2113-M-006-008) is gratefully acknowledged.
stationary phase and hexane–EtOAc as mobile phase. All the
products are known and their characterizations are shown as
follows.
Compound trans-3a:2d 1H NMR (300 MHz, CDCl3): d =
3.19 (m, 1 H), 3.78 (dd, J = 12.8, 3.5 Hz, 1 H), 3.92 (d,
J = 2.1 Hz, 1 H), 4.05 (dd, J = 12.8, 2.1 Hz, 1 H), 7.30 (m, 5
H, Ph). 13C NMR (100 MHz, CDCl3): d = 55.5, 61.2, 62.5,
125.6, 128.2, 128.4, 136.7.
References and Notes
(1) (a) Woodard, S. S.; Finn, M. G.; Sharpless, K. B. J. Am.
Chem. Soc. 1991, 113, 106. (b) Finn, M. G.; Sharpless, K.
B. J. Am. Chem. Soc. 1991, 113, 113. (c) McKee, B. H.;
Kalantar, T. H.; Sharpless, K. B. J. Org. Chem. 1991, 56,
6966. (d) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.;
Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987,
109, 5765. (e) Williams, I. D.; Pedersen, S. F.; Sharpless, K.
B.; Lippard, S. J. J. Am. Chem. Soc. 1984, 106, 6430.
(f) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yasuhiro, Y.;
Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103,
6237. (g) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc.
1980, 102, 5974.
(2) (a) Kelly, A. R.; Lurain, A. E.; Walsh, P. J. J. Am. Chem.
Soc. 2005, 127, 14668. (b) Karjalainen, J. K.; Hormi, O. E.
O.; Sherrington, D. C. Tetrahedron: Asymmetry 1998, 9,
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Perkin Trans. 1 1996, 1729. (d) Petersson, H.; Gogoll, A.;
Backvall, J.-E. J. Org. Chem. 1992, 57, 6025.
Compound syn-3b:9a 1H NMR (300 MHz, CDCl3): d = 1.31
(d, 3 H, J = 6.5 Hz), 3.09 (m, 1 H), 3.95 (d, 1 H, J = 2.1 Hz),
4.10 (m, 1 H), 7.32 (m, 5 H). 13C NMR (100 MHz, CDCl3):
d = 136.9, 128.5, 128.3, 125.7, 65.5, 64.8, 54.6, 18.7.
Compound anti-3b:9a 1H NMR (300 MHz, CDCl3): d = 1.29
(d, 3 H, J = 6.4 Hz), 3.05 (m, 1 H), 3.86 (d, 1 H, J = 2.0 Hz),
3.85 (m, 1 H), 7.30 (m, 5 H). 13C NMR (100 MHz, CDCl3):
d = 136.7, 128.4, 128.2, 125.6, 67.1, 66.4, 56.5, 20.0.
Compound 2b:9b IR (CDCl3): 1678 cm–1; 1H NMR (300
MHz, CDCl3): d = 2.40 (s, 3 H), 6.73 (d, J = 16.0 Hz, 1 H),
7.41 (m, 3 H), 7.51–7.57 (m, 3 H). 13C NMR (100 MHz,
CDCl3) d = 27.5, 127.2, 128.5, 129.1, 130.5, 134.7, 143.5,
198.2. 2c9c: IR (CDCl3): 1705 cm–1; 1H NMR (300 MHz,
CDCl3): d = 2.18 (s, 6 H). 13C NMR (100 MHz, CDCl3): d =
208.1.
Compound 2d:9d IR (CDCl3): 1709 cm–1. 1H NMR (300
MHz, CDCl3): d = 1.70 (m, 2 H), 1.83 (m, 4 H), 2.32 (m, 4
H). 13C NMR (100 MHz, CDCl3): d = 25.1, 27.2, 42.2, 211.8.
Compound 2e:9e IR (CDCl3): 1695 cm–1. 1H NMR (300
MHz, CDCl3): d = 1.23 (t, J = 7 Hz, 3 H), 2.98 (q, J = 7.0 Hz,
2 H), 7.40–7.58 (m, 3 H), 7.98 (m, 2 H). 13C NMR (100
MHz, CDCl3): d = 8.1, 31.9, 127.7, 128.3, 132.8, 137.0,
200.8.
(3) (a) Lu, L. D.-L.; Johnson, R. A.; Finn, M. G.; Sharpless, K.
B. J. Org. Chem. 1984, 49, 728. (b) Klunder, J. M.; Caron,
M.; Uchiyama, M.; Sharpless, K. B. J. Org. Chem. 1985, 50,
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(4) Smith, M. B.; March, J. March’s Advanced Organic
Chemistry: Reactions, Mechanisms, and Structure, 5th ed.;
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Org. Chem. 1996, 61, 1467. (g) Choudary, B. M.;
Compound 2g:9f IR (CDCl3): 1735, 1665 cm–1. 1H NMR
(300 MHz, CDCl3): d = 7.52 (m, 2 H), 7.70 (m, 1 H), 8.21
(m, 2 H), 10.87 (s, 1 H). 13C NMR (100 MHz, CDCl3): d =
129.1, 131.3, 132.2, 136.3, 164.0, 185.2.
Compound 2h:9g IR (CDCl3): 1661 cm–1. 1H NMR (300
MHz, CDCl3): d = 7.46 (m, 4 H), 7.58 (m, 2 H), 7.95 (m, 4
H). 13C NMR (100 MHz, CDCl3): d = 129.2, 129.9, 133.2,
135.0, 194.7.
Durgaprasad, A.; Valli, V. L. K. Tetrahedron Lett. 1990, 31,
5785. (h) Palombi, L.; Bonadies, F.; Scettri, A.; Mincione,
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Yoshida, T.; Nishihara, H.; Ishii, Y.; Ogawa, M. Synth.
Commun. 1986, 16, 537. (j) Masuyama, Y.; Takahashi, M.;
Kurusu, Y. Tetrahedron Lett. 1984, 25, 4417. (k) Kaneda,
K.; Kawanishi, Y.; Jitsukawa, K.; Teranishi, S. Tetrahedron
Lett. 1983, 24, 5009. (l) Bilgrien, C.; Davis, S.; Drago, R. S.
J. Am. Chem. Soc. 1987, 109, 3786. (m) Doyle, M. P.; Dow,
R. L.; Bagheri, V.; Patrie, W. J. J. Org. Chem. 1983, 48,
476. (n) Patil, M. L.; Maujan, S. R.; Borate, H. B.; Uphade,
B. S. ARKIVOC 2007, (i), 70. (o) Jain, S. L.; Sharma, V. B.;
Sain, B. Tetrahedron 2006, 62, 6841. (p) Boudreau, J.;
Doucette, M.; Ajjou, A. N. Tetrahedron 2006, 47, 1695.
(q) Ferguson, G.; Ajjou, A. N. Tetrahedron Lett. 2003, 44,
9139.
Compound 2i:9h IR (CDCl3): 1737, 1670 cm–1. 1H NMR
(300 MHz, CDCl3): d = 1.44 (t, J = 7.0 Hz, 3 H), 4.43 (q,
J = 7.0 Hz, 2 H), 7.47 (m, 2 H), 7.52 (m, 1 H), 8.03 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 14.1, 61.2, 129.3, 131.4,
132.3, 136.5, 163.9, 186.0.
Compound 2j:9i IR (CDCl3): 1666 cm–1. 1H NMR (300 MHz,
CDCl3): d = 0.98 (t, 3 H, J = 7.3 Hz), 1.40 (m, 2 H), 1.60 (m,
2 H), 3.36 (q, J = 7.3 Hz, 2 H), 7.50 (m, 2 H), 7.64 (m, 1 H),
8.35 (m, 2 H). 13C NMR (100 MHz, CDCl3): d = 13.7, 20.1,
31.3, 39.2, 128.5, 131.2, 133.4, 134.3, 161.7, 187.9.
Compound 2k:9j IR (CDCl3): 1710 cm–1. 1H NMR (300
MHz, CDCl3): d = 2.2 (s, 3 H), 2.7 (t, J = 5.5 Hz, 2 H), 3.8
(t, J = 5.5 Hz, 2 H). 13C NMR (100 MHz, CDCl3): d = 30.3,
45.6, 61.1, 208.5.
Compound 2l:9k IR (CDCl3): 1706 cm–1. 1H NMR (300
MHz, CDCl3): d = 1.20 (d, J = 5.8 Hz), 2.18 (s, 3 H), 2.58 (d,
J = 5.8 Hz, 2 H), 4.22 (m, 1 H). 13C NMR (100 MHz,
CDCl3): d = 25.9, 30.6, 51.5, 63.8, 208.9.
(6) Hill, J. G.; Rossiter, B. E.; Sharpless, K. B. J. Org. Chem.
1983, 48, 3607.
(7) The general procedure for alcohol oxidation with TiCl4/
TBHP or Ti(Oi-Pr)4/TBHP is shown as follows. To alcohol
substrate 1 (1 mmol) and 4 Å MS (0.5 g) in CHCl3, CH2Cl2,
or CDCl3 (2 mL) at r.t. was added TiCl4 or Ti(Oi-Pr)4 (0.1
mmol, 10% in CHCl3). The mixture was stirred at r.t. for 1 h.
Toluene solution of TBHP (1.7 mmol) was added into the
mixture, followed by stirring at r.t. or reflux conditions for 1
or 2 d. Low-boiling-point products 2c and 2d were purified
(8) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
(9) (a) Kawakami, T.; Shibata, I.; Baba, A.; Matsuda, H. J. Org.
Chem. 1993, 58, 7608. (b) Murphy, J. A.; Commeureuc, A.
G. J.; Snaddon, T. N.; McGuire, T. M.; Khan, T. A.; Hisler,
K.; Dewis, M. L.; Carling, R. Org. Lett. 2005, 7, 1427.
(c) Amyes, T.; Richard, J. P. J. Am. Chem. Soc. 1992, 114,
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4835. (h) Tatlock, J. H. J. Org. Chem. 1995, 60, 6221.
(i) Chen, J. J.; Deshpande, S. V. Tetrahedron Lett. 2003, 44,
8873. (j) Gogoi, P.; Sarmah, G. K.; Konwar, D. J. Org.
Chem. 2004, 69, 5153. (k) Cardillo, G.; Orena, M.; Porzi,
G.; Sandri, S.; Tomasini, C. J. Org. Chem. 1984, 49, 701.
10297. (d) Ragagnin, G.; Betzemeier, B.; Quici, S.;
Knochel, P. Tetrahedron 2002, 58, 3985. (e) Fujita, K.-I.;
Tanino, N.; Yamaguchi, R. Org. Lett. 2007, 9, 109.
(f) Ohwada, T.; Shudo, K. J. Org. Chem. 1989, 54, 5227.
(g) Okimoto, M.; Itoh, T.; Chiba, T. J. Org. Chem. 1996, 61,
Synlett 2008, No. 7, 1021–1026 © Thieme Stuttgart · New York

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