One-pot synthesis of 1,2,3-triols from allylic hydroperoxides and a catalytic amount of OsO4 in aqueous acetone

Article abstract of DOI:10.1055/s-0029-1217965

Allylic hydroperoxides were converted into the corresponding triols in the presence of a catalytic amount of OsO4. The present reaction involves regeneration of active osmium species by the hydroperoxide functionality and occurs in a diastereoselective manner to form triols in high yields. A plausible mechanism for the formation of 1,2,3-triols from allylic hydroperoxide is presented.

Full text of DOI:10.1055/s-0029-1217965

LETTER
2765
One-Pot Synthesis of 1,2,3-Triols from Allylic Hydroperoxides and a Catalytic
Amount of OsO4 in Aqueous Acetone
S
ynthesis of 1,2,3
e
-Triols malettin Alp, Ufuk Atmaca, Murat Çelik, Mehmet Serdar Gültekin*
Faculty of Sciences, Department of Chemistry, Atatürk University, 25240 Erzurum, Turkey
Fax +90(442)2360948; E-mail: gultekin@atauni.edu.tr
Received 28 May 2009
Grignard reagents; (c) from the reaction of olefins with
Abstract: Allylic hydroperoxides were converted into the corre-
sponding triols in the presence of a catalytic amount of OsO4. The
present reaction involves regeneration of active osmium species by
the hydroperoxide functionality and occurs in a diastereoselective
singlet oxygen; (d) from the solvolysis of alkenyl sulfates
(prepared in situ from equimolar quantities of alcohol and
sulfuric acid) in hydrogen peroxide; (e) from the solvoly-
manner to form triols in high yields. A plausible mechanism for the sis of allylic mesylates and other sulfonate esters in basic
formation of 1,2,3-triols from allylic hydroperoxide is presented.
hydrogen peroxide; and (f) from the nucleophilic dis-
placement of allyl halides with basic hydrogen peroxide.
Key words: osmium tetraoxide, allylic hydroperoxide, triols, in-
tramolecular oxygen transfer
In the initial study, all of the allylic hydroperoxides
(Table 1) were synthesized by photooxygenation of the
corresponding alkenes. These hydroperoxides were then
treated with a catalytic amount of OsO4 in water–acetone
(1:9) solution at room temperature (Scheme 2).
Polyhydroxylated cyclic compounds including conduri-
tols, inositols, allosamidin, and cyclic triols are integral
parts of many important natural products and possess a
wide range of important biological activities such as gly-
cosidase inhibition.1,2 Among the cyclitol family, triols2,3
have attracted much attention due to the fact that they are
precursors to many naturally occurring cyclitols. Triols
are usually prepared by oxidation of the corresponding al-
lylic alcohols with OsO4 or by acid-catalyzed epoxide ring
opening of epoxy alcohols (Scheme 1).4
OH
OOH
OH
OH
a
Scheme 2 General reaction of the formation of 1,2,3-triols.
Reagents and conditions: (a) OsO4 (0.2 mmol%), H2O–acetone (1:9),
r.t.
OH
O
H+, H2O
cis-Dihydroxylation of 17b,c with a catalytic amount of
OsO4 at room temperature for 22 hours provided the cor-
responding rac-2,3-dimethylbutane-1,2,3-triol (2a)4c,8,9 in
high yield. The cyclic hydroperoxides 3, 5, 7, and 9, syn-
thesized as described in the literature, were also subjected
to cis-hydroxylation as reported above to give the rac-
cyclopentane-1,2,3-triol (4a), rac-cyclohexane-1,2,3-triol
(6a), rac-cycloheptane-1,2,3-triol (8a), and rac-cyclo-
octane-1,2,3-triol (10a, Table 1).
OsO4, NMO
OH
HO
OH
OH
Scheme 1 Synthesis of 1,2,3-triols from allylic alcohols and epoxy
alcohols
Due to the high cost and toxicity of OsO4 and environ-
mental concerns, there is a need to use a catalytic amount
of OsO4 with co-oxidants such as hydrogen peroxide,
NMO, NaIO4, or molecular oxygen.5,6
In an ongoing project, we have examined the cis-dihy-
droxylation of the double bond of allylic hydroperoxides
with OsO4 without added co-oxidant in water–acetone.
We found that the hydroperoxide functionality in allylic
hydroperoxides serves as a co-oxidant for regeneration of
active osmium species. This oxidation reaction has been
employed to effect the synthesis of triols via intramolecu-
lar oxygen atom transfer from allyl hydroperoxides.
For characterization of the products, the triols formed
were converted into the corresponding triacetates (4b, 6b,
8b, and 10b) as reported in the literature. The comparison
of the spectroscopic data of the triacetates was completely
in agreement with those given in the literature.11–17
Treatment of rac-2-hydroperoxy-1,2-dihydronaphthalene
(11)18 with OsO4 under the same reaction conditions gave
the expected rac-1,2,3,4-tetrahydronaphthalene-1,2,3-tri-
ol (12a) in moderate yield (61%) along with a mixture of
a-naphthol and b-naphthol 12b (23%) and 12c (16%), re-
spectively (Scheme 3).
Allylic hydroperoxides have been synthesized by various
methods7a (a) from the free-radical autoxidation of ole-
fins, initiated thermally or photolytically; (b) from the au-
toxidation of organometallic compounds, particularly
Our attempt to prepare the triacetate derived from triol
12a failed due to the tendency of the initially formed tri-
acetate to undergo an elimination reaction with base to
form naphthalene derivatives.
SYNLETT 2009, No. 17, pp 2765–2768
x
x
.x
x
.2
0
0
9
Advanced online publication: 09.09.2009
DOI: 10.1055/s-0029-1217965; Art ID: D13609ST
© Georg Thieme Verlag Stuttgart · New York

2766
C. Alp et al.
LETTER
Table 1 The Triols (1,2,3) from Reactions of Allylic Hydroperox-
OH
OH
ides with a Catalytic Amount of OsO4
OH
OH
a
+
0.2 mmol% OsO4
1–13
2a–14a
OOH
H2O–acetone (1:9), r.t.
11
12a
12b
Entry Substratea
Yield Triolc
(%)b
Yield Time
(%)d (h)
+
OH
OH
OH
12c
1
997c
86
84
22
36
OOH
Scheme 3 Oxidation reaction of 2-hydroperoxy-1,2-dihydro-naph-
thalene (11) with a catalytic amount of OsO4. Reagent and conditions:
(a) OsO4 (0.2 mmol%), H2O–acetone (1:9), 42 h, r.t., 92%, ratios of
products 12a/12b/12c = 6.1:2.3:1.6.
HO
2a4,8,9
17
OH
OOH
HO
2
7810b
O
O
O
OH
HO
4a3,8,11
HO
HO
310
HO
a
+
+
+
OH
OOH
HO
3
6612c
94
90
82
61
36
37
28
42
OOH
OH
14a
OH
14b
13
14c
14d
HO
6a8,11,13
5 7a,12
Scheme 4 Oxidation reaction of a,b-unsaturated hydroperoxide 13
with a catalytic amount of OsO4. Reagent and conditions: (a) OsO4
(0.2 mmol%), H2O–acetone (1:9), 65 h, r.t., 95%, ratios of products
14a/14b/14c/14d = 3:5.1:1.1:0.8.
OH
OOH
HO
4
6014b
HO
8a8,15
ucts. Again, the acetylation of 14a failed due to aromati-
714
zation (Scheme 4).
OH
HOO
For further characterization, the triols formed (4a, 6a, 8a,
and 10a) were converted into the corresponding acetates
(4b, 6b, 8b, and 10b, respectively), the triacetates were
prepared as in the literature4a,12 (Scheme 5).
HO
5
8010b
HO
919
10a8,15,17
OH
The triols (4a, 6a, 8a, 10a, 12a, and 14a) were established
by comparison of their spectroscopic data with those re-
ported in the references (Table 1).
OH
OH
6
5318b
OOH
1118
12a8,19
OH
OAc
HO
AcO
O
O
a
(CH2)n
(CH2)n
HO
HO
AcO
7
9020a
30
65
HO
n = 1, 4a
n = 1, 4b (78%)
n = 2, 6b (81%)
n = 3, 8b (74%)
n = 4, 10b (71%)
n = 2, 6a
n = 3, 8a
n = 4, 10a
HOO
1320
HO
14a8
Scheme 5 Acetylation reaction of cyclic triols. Reagent and condi-
tions: (a) pyridine (10 mL), 0 °C, 0.5 h, then Ac2O (4 equiv), r.t., over-
night.
a The references are for the allylic hydroperoxides.
b The references are for the isolated yields of allylic hydroperoxides.
c The references are for the corresponding triols.
d The isolated yields are for triols from allylic hydroperoxides.
When compounds 12a and 14a were treated with pyridine
and Ac2O at room temperature, these molecules were con-
verted into the corresponding aromatic derivatives.
Finally, we applied an OsO4-catalyzed reaction to an alk-
ene 1320a having an electron-deficient double bond. a,b-
Unsaturated ketohydroperoxide 13 was reacted with a cat-
alytic amount of OsO4 as described before. In contrast to
the other hydroxylations, the reaction was completed over
a longer time (~ 3 d) and in lower yield. Beside the expect-
ed rac-2,3,4-trihydroxy-4-methylcyclohexanone (14a,
30%), the reduction product rac-4-hydroxy-4-methyl-
cyclohex-2-enone 14b,20a 51%) was formed as the major
product. The aromatization products, p-cresol (14c, 11%)
and m-cresol (14d, 8%) were formed as the minor prod-
For the formation of triols we suggest the following reac-
tion mechanism (Scheme 6). We assume that OsO4 first
undergoes a stereodirected [3+2] cycloaddition to the
double bond. It is well established that the initially formed
osmate ester 15 is an energetically more favorable inter-
mediate.21 The osmate ester 15 undergoes hydrolysis with
water to give cis-vicinal diol and releases reduced
Os(VI)O3, which is reoxidized by the hydroperoxide func-
tionality back to Os(VIII)O4.
Synlett 2009, No. 17, 2765–2768 © Thieme Stuttgart · New York

LETTER
Synthesis of 1,2,3-Triols
2767
Synthesis, Vol. 36; Thieme: Stuttgart, 2007, 799.
O
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OH
HO
OH
(8) Typical Procedure for the Formation of Triols
Allylic hydroperoxide (10 mmol) was dissolved in a mixture
of H2O–acetone (20 mL, 1:9) solution and OsO4 (0.02 mmol,
5 mg) in acetone (5 mL) was added to the stirring solution of
hydroperoxide. The mixture was stirred at r.t. at 22–65 h
(examples in Table 1). The reaction was monitored by TLC.
The solution was evaporated (2.7·10–2 bar, r.t.), and then the
crude residue was directly purified by column
6a
Scheme 6 Mechanism for the formation of 1,2,3-triols from allylic
hydroperoxides with a catalytic amount of OsO4
In the methodology described here, it is not necessary to
use a co-oxidant. The hydroperoxide group serves as the
co-oxidant and that enables the use of a catalytic amount
of OsO4 as a reagent. All of the hydroperoxides are con-
verted into corresponding products in almost quantitative
yields.
chromatography on silica gel using EtOAc–hexanes as
eluent to give the corresponding triols (Table 1).
rac-2,3-Dimethylbutane 1,2,3-Triol (2a)
1H NMR (200 MHz, CDCl3): d = 1.02 (s, 3 H), 1.18 (s, 3 H),
1.21 (s, 3 H), 3.44 (d, J = 11.3 Hz, 1 H), 3.83 (d, J = 11.3, 1
H) ppm. 13C NMR (50 MHz, CDCl3): d = 22.1, 26.6, 27.2,
70.1, 77.5, 77.9 ppm.
Thus, our novel triol-synthesis procedure described herein
will provide a new alternative method for triols. Applica-
tion of this triol-synthesis reaction will be presented, par-
ticularly in the synthesis of cyclitols in the near future.
rac-Cyclopentane-1,2,3-triol (4a)
1H NMR (200 MHz, CD3OD): d = 1.39–1.83 (m, 2 H), 1.91–
2.18 (m, 2 H), 3.69–3.79 (m, 1 H), 4.01–4.12 (m, 2 H) ppm.
13C NMR (50 MHz, CD3OD): d = 31.5, 31.8, 74.6, 79.2, 82.7
ppm.
rac-Cyclopentane-1,2,3-triyl Triacetate (4b)
1H NMR (200 MHz, CDCl3): d = 1.49–1.61 (m, 1 H), 1.74–
1.81 (m, 1 H), 2.02 (br s, 9 H, 3 CH3), 2.23–2.44 (m, 2 H),
5.09–5.23 (m, 2 H), 5.28 (m, 1 H) ppm. 13C NMR (50 MHz,
CDCl3): d = 22.5, 22.6, 22.8, 28.6, 28.8, 74.1, 77.9, 78.4,
171.8, 171.9, 172.2 ppm.
Acknowledgment
The authors are indebted to the Department of Chemistry and Ata-
türk University for its financial support of this work.
rac-Cyclohexane-1,2,3-triol (6a)
References and Notes
1H NMR (200 MHz, CD3OD): d = 1.20–1.87 (m, 6 H), 3.34
(dd, J = 2.7, 8.5 Hz, 1 H), 3.75 (m, 1 H), 4.01 (m, 1 H) ppm.
13C NMR (50 MHz, CD3OD): d = 21.3, 33.5, 34.9, 72.9,
73.1, 79.1 ppm.
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1H NMR (200 MHz, CDCl3): d = 1.57–1.97 (m, 6 H), 2.01
(s, 3 H), 2.05, (s, 3 H), 2.19, (s, 3 H), 4.90 (dd, J = 3.0, 9.1
Hz, 1 H), 5.05 (m, 1 H), 5.32 (m, 1 H) ppm. 13C NMR (50
MHz, CDCl3): d = 20.3, 22.5, 22.8, 23.9, 29.9, 30.8, 71.9,
72.3, 74.4, 168.1, 171.8, 171.9 ppm.
rac-Cycloheptane-1,2,3-triol (8a): 1H NMR (200 MHz,
CD3OD): d = 1.45–1.88 (m, 8 H), 3.55 (dd, J = 2.5, 7.1 Hz,
2 H), 3.70 (m, 1 H), 3.96 (m, 1 H) ppm.13C NMR (50 MHz,
CD3OD): d = 25.4, 26.3, 33.4, 35.8, 74.6, 75.3, 82.2 ppm.
rac-Cycloheptane-1,2,3-triyl Triacetate (8b): 1H NMR
(200 MHz, CDCl3): d = 1.42–1.66 (m, 8 H), 2.02 (s, 3 H),
1.99 (s, 3 H), 1.97 (s, 3 H), 4.86 (dd, J = 2.0, 4.2, 1 H), 4.95
(m, 1 H), 5.06 (m, 1 H) ppm. 13C NMR (50 MHz, CDCl3): d
= 22.7, 22.8, 22.9, 23.8, 24.0, 29.7, 29.9, 73.9, 74.4, 78.05,
171.8 (2 C), 171.9 ppm.
rac-Cyclooctane-1,2,3-triol (10a): 1H NMR (200 MHz,
CD3OD): d = 1.55–1.90 (m, 10 H), 3.65 (dd, J = 2.4, 8.5 Hz,
Synlett 2009, No. 17, 2765–2768 © Thieme Stuttgart · New York

2768
C. Alp et al.
LETTER
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79.9, 209.8 ppm.
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