Selective oxidation of benzylic or allylic hydroxyl group of sec-1,2-diols

Article abstract of DOI:10.1016/j.tetlet.2004.12.073

A mild and efficient method to selectively oxidize chiral sec-1,2-diols has been developed, which demonstrates that 2,3-dichloro-5,6-dicyano-1,4- benzoquinone (DDQ) can selectively oxidize benzylic or allylic hydroxyl group of sec-1,2-diols under ultrasound wave promotion. The configuration of the adjacent chiral center is retained.

Full text of DOI:10.1016/j.tetlet.2004.12.073

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1217–1220
Selective oxidation of benzylic or allylic hydroxyl group
of sec-1,2-diols
Kun Peng,a Fuxin Chen,a Xuegong She,a,b,* Chunhui Yang,c Yuxin Cuic and Xinfu Pana,*
aDepartment of Chemistry, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
bState Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics,
Chinese Academy of Sciences, Lanzhou 730000, PR China
cMedical and Healthy Analysis Center, Peking University, Beijing 100083, PR China
Received 19 August 2004; revised 4 November 2004; accepted 10 December 2004
Available online 8 January 2005
Abstract—A mild and efficient method to selectively oxidize chiral sec-1,2-diols has been developed, which demonstrates that
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) can selectively oxidize benzylic or allylic hydroxyl group of sec-1,2-diols under
ultrasound wave promotion. The configuration of the adjacent chiral center is retained.
Ó 2004 Elsevier Ltd. All rights reserved.
Enantiomerically pure a-hydroxy ketones are important
synthons for the asymmetric synthesis of many natural
products. This structure unit is commonly found in such
biologically active natural products as sugar, phero-
mones, antibiotics, terpenes and alkaloids. Many meth-
ods of synthesis of this structure have been reported, for
example, the reduction of diketones by yeast,1 the asym-
metric oxidation of ketone enolates2,3 by enantiomeri-
cally pure aprotic oxidizing reagents. However, the
reagents that they used are either expensive or difficult
to prepare.
propane-1,2-diol,10 respectively. Under the condition
of their experiments, the reaction needs heating, and
the reaction times are longer than 12 h. The major
reason that causes this difficulty of selective oxidation
is that the two hydroxyl groups of sec-1,2-diols have lit-
tle difference at chemical- and stereo-environment. To
solve this problem, our efforts are aimed mainly at two
sides, (1) selection of suitable oxidant, (2) seeking for
suitable reaction condition to achieve the selective oxi-
dation and decrease the byproducts (diketones and
product of the cleavage of 1,2-diols).
One of the simplest way to prepare chiral a-hydroxy
ketone is selective oxidation of asymmetric sec-1,2-diols,
which can be easily done by the Sharpless asymmetric
dihydroxylation. Many reports on selective oxidation
focus on primary hydroxyl group of diols4 or one
hydroxyl group of diols that have the same chemical
environment.5–7 A remarkable total synthesis work
involves the selective oxidation of benzylic hydroxyl
group, but the hydroxyl groups in this synthesis work
are not at vicinal position, and the other hydroxyl
groups have been protected before oxidation.8 The Ga-
nemÕ group and LeyÕs group reported selective oxidation
of cyclohexenediol9 and 1-(3,4,5-trimethoxy-phenyl)-
After many trials, it is found that DDQ can not only effi-
ciently oxidize the benzylic hydroxyl group as litera-
ture11 reported, but can also work well in selective
oxidation of sec-1,2-diols (Scheme 1). Some substrates
(entry 5 and 10) can react quickly at room temperature,
which is as similar as FerreiraÕs group reported,12 but
most substrates react slowly at room temperature and
some substrates cannot even react (entries 7 and 8).
Under the reflux condition, the products were compli-
cated due to overoxidation. Therefore, it is very valuable
HO
OH
O
OH
DDQ
*
*
*
R1
R2
R1
R2
ultrasound wave
R1= Alkenyl, Phenyl
R2= Alkyl
Keywords: Selective oxidation; DDQ; Ultrasound wave; Vicinal
position.
*
Corresponding authors. Tel.: +86 9318912407; fax: +86 9318912582
(X.S.); e-mail addresses: shexuegong@yahoo.com; panxf@lzu.edu.cn
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.12.073

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K. Peng et al. / Tetrahedron Letters 46 (2005) 1217–1220
Table 1. Selective oxidation of diols to a-hydroxy ketones by using DDQ
Entry Time (h)
Diolsa Conditionsb
OH
22
½aꢀD
Products
Yieldc (%)
Ratiod
>9:1
OH
OCH3
OCH3
1
(a)
5
72
ꢁ31
ꢁ32
OH
OH
O
HO
(1) (S,S)
OCH3
OCH3
H3CO
OCH3
H3CO
OCH3
2
(a)
5
82
>9:1
OH
OH
HO
O
(2) (S,S)
OCH2OCH3
OCH3
OCH2OCH3
OCH3
3
(a)
5
84
>9:1
+24
OH
OH
O
HO
(3) (R,R)
O
O
O
O
4
5
6
(a)
(a)
(a)
5
5
5
79
79
67
>9:1
>9:1
>8:1
ꢁ25
ꢁ19
OH
OH
O
HO
(4) (S,S)
OH
OH
O
H3CO
H3CO
OH
CH3
CH3
CH3
CH3
O
O
(5) (S,R)
CH3
CH3
OH
(6) (S)
OH
O
HO
Cl
(a)
(b)
No reaction
7
Cl
OH
(7) (S,S)
HO
5
56
>9:1
ꢁ27
OH
O

K. Peng et al. / Tetrahedron Letters 46 (2005) 1217–1220
1219
Table 1 (continued)
Entry
Diolsa
NO2
22
½aꢀD
Conditionsb
Time (h)
Products
Yieldc (%)
Ratiod
(a)
(b)
No reaction
Product complex
8
>5
OH
HO
(8) (S,S)
(a)
(b)
No reaction
OH
COOBu
OH
9
OH
OH
COOBu
(9) (S,S)
7
2
34
62
>6:1
>8:1
ꢁ7
O
OH
Ph
Ph
10
(a)
+29
Ph
Ph
OH
(10) (S,S)
O
a The substrate was prepared by Sharpless asymmetric dihydroxylation with AD-mix a or with AD-mix b.
b (a) Anhydrous benzene, ultrasound wave, rt, 2 Mequiv of DDQ; (b) anhydrous benzene, reflux, 2 Mequiv of DDQ.
c The yields were determined by isolation.
d The ratio (a-hydroxy ketone/diketones) was calculated by isolation yields.
to find one general and mild reaction condition, which
can be suitable for various substrates.
tained under condition b. Nitryl of entry 8 may be has
a too strong electronegativity, so its product in condi-
tion b was very complex. The last substrate (entry 10)
was designed to have both benzylic hydroxyl and allylic
hydroxyl groups that are at vicinal position, but the re-
sult is against our expectation. It is very interesting that
the allylic hydroxyl group was oxidized preferentially.
As for this point, we will continue to study it in our fu-
ture work. Thirdly, the transformation of the diols into
a-hydroxy ketone occurs selectively with practically
retention of configuration at the remained chiral cen-
ter.15 It will be very useful in organic synthesis.
In recent years, the ultrasound wave promotion
reactions have been widely applied in modern organic
synthesis. It offers the potential tools for shorter
reaction time. The influence of ultrasonic energy on
chemical activities may involve any or all of the follow-
ing, production of heat, facilitation of mixing, enhance-
ment of intimate contact.13 Under the promotion of
ultrasound, it is found that selective oxidation reaction
of sec-1,2-diols can proceed very well by using DDQ
as an oxidation reagent in anhydrous benzene.
Under this condition, several different diols were selec-
tively oxidized to the corresponding a-hydroxy ketones
(Table 1).
In conclusion, a mild, economic and efficient way is found
to selectively oxidize sec-1,2-diols in good yields by using
easily obtained DDQ. The generality of this method has
been proved, and this new approach shows the consider-
able practical value due to its efficiency and simplicity.
The above results revealed some important information.
Firstly, most substrates with benzylic hydroxyl group re-
act faster than those with allylic hydroxyl group. The
substrates with benzylic hydroxyl group can be oxidized
in mild condition (condition a) and the products were
obtained in good yields (entries 1–5), but the substrates
with allylic hydroxyl group were oxidized very slowly
under the same condition (entry 9). Entry 9 was also
tried under reflux condition (condition b) and the ex-
pected product was obtained, but yields were still low
as we supposed. In our experiment, it was found that
DDQ can also efficiently selectively oxidize secondary
hydroxyl group of primary, secondary-1,2-diols (entry
6). Secondly, the electronic property of substituent can
influence this reaction. If the substituent is an electron-
donating group, the reaction react more quickly in mild
condition a. Whereas entries 7 and 8 did not work in
condition a. In entry 7, the expected product was ob-
Acknowledgements
This work was supported by NSFC (QT program and
No. 2037 2026), SRF for ROCS.SEM, Gansu Science
Foundation (No. YS031-A21-001) and hundred talents
scientist program.
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15. The absolute configuration of a-hydroxy ketones are
determined by MosherÕs method. Typical procedures for
preparation of (R)-and (S)-MTPA esters.14 (R)-MTPA
ester of 2-hydroxy-1-(3-methoxy-4-(methoxymethoxy)-
phenyl)-propan-1-one (entry 3). To
a solution of
2-hydroxy-1-(3-methoxy-4-(methoxymethoxy)phenyl)-propan-
1-one (8 mg, 33.3 mmol) in CH2Cl2 (1 mL), was added
(+)-MTPA chloride (66.7 mmol, 12 lL), TEA (0.05 mmol,
7 lL), DMAP (catalytic quantity) and the solution is allowed
to stand at room temperature for 30 min. the residue
was purified by column chromatography on silica gel. The
results are very satisfactory according to our conclusion, and
the ee% of products obtained form NMR are above 85%.