Conversion of racemic allylic hydroperoxides into corresponding chiral 1/2,3-triols by using catalytic OsO4 and chiral cinchona ligands in the absence of co-oxidant

Article abstract of DOI:10.3906/kim-1411-68

For the first time, removal of oxygen atoms from allylic hydroperoxide functionality and reintroduction to the double bond was achieved using catalytic OsO₄ and chiral cinchona alkaloid derivatives in an acetone-water mixture to give corresponding chiral 1/2,3-triol with an enantioselectivity up to 99% ee. The hydroperoxide group was used as both a co-oxidant and a source of hydroxyl groups. This protocol is thought to have potential to provide opportunities for chiral synthesis of 1/2,3-triols from corresponding allylic hydroperoxides in the absence of co-oxidant in one stage for the first time in the literature.

Full text of DOI:10.3906/kim-1411-68

Turk J Chem
Turkish Journal of Chemistry
(2015) 39: 824 – 834
¨
http://journals.tubitak.gov.tr/chem/
˙
c
⃝ TUBITAK
doi:10.3906/kim-1411-68
Research Article
Conversion of racemic allylic hydroperoxides into corresponding chiral 1/2,3-triols
by using catalytic OsO4 and chiral cinchona ligands in the absence of co-oxidant
1,2
Haydar GOKSU , Mehmet Serdar GULTEKIN
2,∗
¨
¨
˙
1Kayna¸slı Vocational College, Du¨zce University, Du¨zce, Turkey
2Department of Chemistry, Faculty of Sciences, Atatu¨rk University, Erzurum, Turkey
Received: 26.11.2014
•
Accepted/Published Online: 13.05.2015
•
Printed: 28.08.2015
Abstract:For the first time, removal of oxygen atoms from allylic hydroperoxide functionality and reintroduction to the
double bond was achieved using catalytic OsO4 and chiral cinchona alkaloid derivatives in an acetone–water mixture
to give corresponding chiral 1/2,3-triol with an enantioselectivity up to 99% ee. The hydroperoxide group was used as
both a co-oxidant and a source of hydroxyl groups. This protocol is thought to have potential to provide opportunities
for chiral synthesis of 1/2,3-triols from corresponding allylic hydroperoxides in the absence of co-oxidant in one stage for
the first time in the literature.
Key words: Chiral 1/2,3-triols, chiral cinchona alkaloids derivatives, allylic hydroperoxide, intramolecular atom transfer.
1. Introduction
Polyhydroxylated organic compounds including inositols, quercitols, conduritols, glucose, glycerol, ethylene
glycol, and cyclic triols are an important class of compounds found in plants and they are often used in the
production of industrial materials.1,2 Additionally, most cyclitols possess a wide range of important biological
activities such as glycosidase inhibitory effect and antibiotic effect.3−6 Recently, the enantioselective synthesis of
polyhydroxylated organic compounds has received considerable attention due to their useful biological activity
and synthetic utility.7,8 Consistently increasing demand for the production of enantiomerically pure compounds
has led to the development of different strategies for the synthesis of chiral compounds. Among the employed
strategies, asymmetric synthesis has an important place, as it represents an efficient access to the required
enantiomer.9
Asymmetric synthesis of biologically active cyclitols and derivatives plays an important role in synthetic
organic chemistry.10−17 In particular, asymmetric construction of 1,2,3-triols is a key transformation in the
synthesis of polyhydroxyl groups.18
Sharpless was the first to develop an asymmetric syn dihydroxylation reaction of olefins using a catalytic
amount of OsO4 and cinchona alkaloid as a chiral ligand in the presence of co-oxidants such as hydrogen
peroxide, N-methylmorpholine oxide N-oxide (NMO), NaIO4 , or molecular oxygen.18−21
Recently we reported osmium-catalyzed racemic synthesis of 1/2,3-triols from corresponding allylic hy-
droperoxides, without the need for co-oxidant, in an acetone–water mixture (9:1) (Scheme 1, method A).22 Ad-
∗Correspondence: gultekin@atauni.edu.tr
On the occasion of his retirement, we dedicate this paper to our supervisor Prof Dr Metin BALCI
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ditionally, analogous reactions of intramolecular oxygen atom transfer were achieved by zeolite-confined osmium
(0) nanoclusters as the result of the synthesis of racemic 1/2,3-triols from corresponding allylic hyroperoxides
in the absence of co-oxidant (Scheme 1, method B).23
Reaction conditions, method A: cat.OsO4, acetone-water (9:1), rt, 30 -94% in 7 examples, 22-65 h.
Method B: 0.01 mmol% zeolite-Os (0), acetone: water (4:1), rt, 58-93% in 10 examples, 36-60 h.
Scheme 1. One-pot synthesis of racemic 1/2,3-triols from racemic allylic hydroperoxides.22,23
In Scheme 1, oxidation reactions were evolved to effectuate the synthesis of various racemic 1/2,3-triols
via intramolecular oxygen atom transfer from racemic allylic hydroperoxides in the absence of co-oxidant. On
the other hand, these two methods were also the pioneering examples for the synthesis of 1/2,3-triols from allylic
hydroperoxides via intramolecular oxygen atom transfer.
With this background, the objective of the present study was to develop an asymmetric version of this
catalytic reaction. For this purpose, chiral cinchona alkaloid derivatives were used as chiral ligands with a
catalytic amount of OsO4 in an acetone–water mixture at room temperature. As expected, intramolecular
oxygen atom transfer from the allylic hydroperoxide group to the double bond of the same molecule was
achieved under mild conditions. In this protocol, an easy, facile, and applicable method was employed for the
synthesis of chiral 1/2,3-triols. An effective method for the one-pot synthesis of 1/2,3-triols involves chiral
cinchona alkaloids and the hydroperoxide group serving as both the co-oxidant and substrate. The use of
cinchona alkaloids provides chirality, oxygen atom on the hydroperoxide group, and cat. OsO4 oxides to the
double bond on allylic hydroperoxide containing racemic olefins in acetone/water media.
2. Results and discussion
Some chiral cinchona alkaloids, 1b, 1c, 1d, and 1e, were prepared according to the literature procedures,14−17
and other chiral cinchona ligands, 1a, 1f, and 1g, were obtained from chemical suppliers (Figure).
As reported in the literature, when an amount of catalytic OsO4 was used with chiral cinchona alkaloids
in the dihydroxylation reaction of olefins, enantiomeric excess was quite high.20 According to information based
on the literature, the chiral ligands 1a–g were treated with an equivalent amount of osmium tetraoxide, used
as catalyst, in the synthesis of asymmetric triols in this study.
The cyclic or linear allylic hydroperoxides 2a–g were prepared by the photooxygenation of corresponding
alkenes.17,24−32 For each of the allylic hydroperoxides, enantioselectivity and catalytic activity of the composed
reaction solution were examined. Hence, the reaction temperature and the amount of chiral ligand were
measured, while some findings about molecular structure were obtained for the developed asymmetric reaction.
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Figure. Chiral cinchona ligands used in this work.
In initial experiments in the present study, as a selected sample molecule 3-hydroperoxycyclopent-1-ene
(2a) was reacted with ligand 1a–g in the presence of cat. OsO4 at a constant temperature and time (at –20
◦ C, in 30 min) in a solvent mixture such as acetone/water (4/1) (Table 1). To investigate the synthesis of
racemic triols, the chiral ligand QD 1a and cat. OsO4 were primarily chosen and then other chiral ligands were
tested in the presence of cat. OsO4 , including QDAc 1b, QDSiMe3 1c, QDBz 1d, QDTs 1e, (QD)2 PHAL
1f, and (QD)2 PYR 1g to optimize the reaction conditions. Among the chiral ligands, QDSiMe3 1c was the
most effective in the synthesis of chiral-cyclopentane-1/2,3-triol (3a) with a yield of 45%. The chiral triol 3a
was converted into corresponding chiral 1/2,3-triacetate 3aa derivative [α]2D5 = −47 (c 0.5, MeOH, 32% ee) for
structural characterization and HPLC analysis (Table 1, entry 3; see supporting information, on the journal’s
website).
Results in assays performed with different amounts of QDSiMe3 1c and cat. OsO4 show that 2.6
mmol of hydroperoxides using as starting material with 0.4 mol % of QDSiMe3 1c and cat. OsO4 would be
a more suitable system in enantioselectivity and synthesis of corresponding asymmetric 1/2,3-triol 3a. The
chiral triol 3a was converted into corresponding 3aa (Table 1, entry 9) and the conversion yield of 3a was also
quite high under these reaction conditions (conv. 92%). Although there were 1/2,3-triol molecules in higher
conversion yields in Table 1, the high enantioselectivity reactions were taken into account. The reaction had
to be interrupted at an appropriate time in order to capture high enantioselectivity; otherwise, a considerable
increase would be seen in the racemic triols rate in the result of the reaction.
After determining the ligand type and ligand/OsO4 rate, the effects of different parameters such as
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Table 1. Effects of chiral ligands (1a–g) and cat. OsO4 in the synthesis of chiral cyclopentane-1/2,3-triol 3aa and its
conversion into chiral chiral cyclopentane-1/2,3-triyl triacetate 3aa.d
OsO4
Ligand
Conversion
Entry
Yield (%)c ee (%)d
(mol %) (1a–g) (mol %) (%)b
1
2
3
4
5
6
7
7
8
0.1
0.1
0.1
0.1
0.1
0.1
0.1
1.0
0.2
0.4
0.6
1a (0.1)
1b (0.1)
1c (0.1)
1d (0.1)
1e (0.1)
1f (0.1)
1g (0.1)
1c (1.0)
1c (0.2)
1c (0.4)
1c (0.6)
88
85
88
85
86
88
86
98
90
92
93
78
75
45
55
82
67
68
85
65
58
68
6
12
32
28
5
10
20
15
22
36
19
9
10
a The reaction was carried out with 2a (2.6 mmol) in acetone/water (v/v = 4/1) in 30 min at –20 ◦ C in the presence
of OsO4 and chiral ligand.
b For 3a, determined by 1 H NMR,
c Total isolated yields of enantiomers from 2a to 3aa,
d For 3aa, determined by HPLC with a Chiralcel AS column.
reaction time and temperature on the reactivity and enantioselectivity were investigated (Table 2). At the end
of the trial studies, the reaction conditions giving the highest conversion and enantioselectivity were determined.
It was found that temperature and reaction time play a crucial role in the synthesis of asymmetric 1/2,3-triols
(Table 2, entries 1–11).
When the reaction was carried out with increasing time (30, 45, and 60 min) at the same temperature
(such as –20 ◦ C), for cyclopentane-1/2,3-triol (3a) conversion increased from 88% to 92%, yield from 45% to
58%, and ee from 32% to 36% (Table 2, entries 1–3). The chiral triacetate 3aa was prepared from chiral triol 3a
with acetic anhydrate in pyridine. Optical rotatory of the chiral triacetate 3aa was identified (Table 3, entries
1–3). The same conditions were applied to 3-hydroperoxycyclopent-1-ene (2a) at –40 ◦ C for synthesis of chiral
triols 3a and in the result of the reaction synthesized chiral triol 3a was convert to 3aa in Ac2 O/pyridine
solvent mixture; differences were observed in ee values of cyclopentane-1/2,3-triacetate (3aa): 16% ee in 30
min, 18% ee in 45 min, and 7% ee in 60 min (Table 2, entries 4–6).
When the reaction was carried out with increasing time as in entries 1–3 and at –70 ◦ C, ee values of
cyclopentane-1/2,3-triacetate (3aa) increased, although some differences were observed in conversions and yields
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Table 2. Effects of temperature and time in the synthesis of chiral cyclopentane-1/2,3-triol 3aa and its conversion into
chiral chiral cyclopentane-1/2,3-triyl triacetate 3aa.e
Temperature
Conversion
Entry
Time (min)
Yield (%)d ee (%)e
(◦C)b
–20
–20
–20
–40
–40
–40
–70
–70
–70
0
(%)c
88
90
92
68
73
78
50
48
1
2
3
4
5
6
7
8
9
30
45
60
30
45
60
30
45
60
30
60
45
46
58
35
40
45
20
25
41
35
52
32
33
36
16
18
7
4
9
20
15
46
60
92
99
10
11
0
a The reaction was carried out with 2a (2.6 mmol) in acetone/water (v/v = 4/1) at the corresponding temperatures and
in times in the presence of OsO4 (0.4 mol %) and 1c (0.4 mol %).
b Adjusted by Cryostat.
c For 3a, determined by 1 H NMR,
d Total isolated yields of enantiomers from 2a to 3aa,
e
For 3aa, determined by HPLC with a Chiralcel AS column.
(Table 2, entries 7–9). However, ee values of cyclopentane-1/2,3-triacetate (3aa) at –40 ◦ C and –70g◦ C were
lower than those at –20 ◦ C. It should be noted that the ee values of cyclopentane-1/2,3-triacetate (3aa) seem
to be reduced as the temperature decreases. When the reaction temperature increased to 0 ◦ C, cyclopentane-
1/2,3-triol (3a) was obtained with a yield of 35% in 30 min and 52% in 60 min (Table 2, entries 10 and 11). It
was determined that the reaction conditions such as 0 ◦ C and 1 h were the most effective in the synthesis of
cyclopentane-1/2,3-triol (3a) and the product was obtained in 99% conversion of cyclopentane-1/2,3-triol (3a)
with 46% ee of cyclopentane-1/2,3-triacetate (3aa) (Table 2, entry 11).
Corresponding asymmetric 1/2,3-triols were synthesized from racemic allylic hydroperoxides using the
optimized conditions as a result of experiments. The results of the reaction of QDSiMe3 1c/cat. OsO4 with
various allylic hydroperoxides and the acetate derivatives of some asymmetric 1/2,3-triols are summarized in
Table 3. For the characterization and HPLC analyses of some chiral triols, 3a, 3b, 3c, 3d, and 3e, these triols
were converted into the corresponding triacetates 3aa, 3bb, 3cc, 3dd, and 3ee as reported in the literature.
However, some triols such as 3h and 3g were not converted into corresponding acetates, because the triols 3g
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Table 3. Synthesis of chiral 1/2,3-triols from racemic allylic hydroperoxidesa and its conversion into chiral 1/2,3-
triacatate.
[α]2D5e
b
Conversion (%) Yields (%) ee (%)
c
d
Entry Substrate
Product
1
99
99
52
44
46
25
-47.0
2a
3aa
2
+10.0
2b
3bb
3
98
58
41
-2.0
2c
3cc
4
92
98
60
55
35
90
+5.0
-7.0
2d
3dd
5
2e
3ee
3f
6
99
99
48
54
99
89
+28.0
+25.0
2f
7
2g
3g
a The reaction was carried out with 2a–g (2.6 mmol) in acetone/water (v/v = 4/1) at 0 ◦ C and in 1 h in the presence
of OsO4 (0.4 mol %) and 1c (0.4 mol %).
b For the triols (3a, f , g), determined by 1 H NMR.
c Total isolated yields of enantiomers from 2a–e to 3aa–ee and total isolated yields of enantiomers from 2f, g to 3f, g.
d For 3aa–3ee, determined by HPLC with a Chiralcel AS column.
e Determined by ADP 220 Bs polarimeter.
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and 3h were decomposed into reaction media. NMR spectroscopic data of the triacetates were completely in
agreement with those given in the literature.22
The results show that the structures of allylic hydroperoxides had a considerable influence on the
enantioselectivity. The use of chiral cinchona alkaloids as chiral catalysts for the trihydroxylation of allylic
hydroperoxides offers an attractive means of accomplishing this reaction. It can be summarized that the allylic
hydroperoxides that have five, six, and seven carbon membered rings led to lower enantioselectivities (Table 3,
entries 1–4), whereas straight carbon chain and wide ringed allylic hydroperoxides were more selective (Table
3, entries 5–8).
As the result of this asymmetric reaction, rac-3-hydroperoxycyclopent-1-ene (2a) was converted into
chiral cyclopentane-1/2,3-triol (3a) with the yield of 52% and for 3aa 46% ee (Table 3, entry 1). rac-3-
Hydroperoxycyclohex-1-ene (2b) was oxidized to chiral cyclohexane-1/2,3-triol (3b) with the yield of 44% and
for 3bb 25% ee (Table 3, entry 2). The reaction of rac-3-hydroperoxy-7-oxabicyclo [4.1.0] hept-4-ene (2c) with
1c/OsO4 gave chiral 7-oxabicyclo [4.1.0] heptane-2/3,4-triol (3c) in the yield of only 58% and for 3cc 41%
ee (Table 3, entry 3). rac-3-Hydroperoxycyclohept-1-ene (2d) was converted into chiral cycloheptane-1/2,3-
triol (3d) in the yield of 60% and for 3dd 35% ee (Table 3, entry 4). rac-3-Hydroperoxycyclooct-1-ene (2e),
rac-3-hydroperoxy-2,3-dimethylbut-1-ene (2f), and rac-3-hydroperoxybut-1-ene (2g) gave the products chiral
cyclooctane-1/2,3-triol (3e), chiral 2,3-dimethylbutane-1/2,3-triol (3f), and chiral butane-1/2,3-triol (3g) with
ee values (for cyclohexane 1/2,3-triacetate (3ee) 90% ee, for 3f 99% ee, and for 3g 89% ee, respectively) higher
than 3aa–dd (Table 3, entries 5–7). All racemic 1/2,3-triols and 1/2,3-triacetates were identified by 1 H and
13 C NMR spectroscopy in comparison with literature data.22,23 The ratios of enantiomers for chiral 1/2,3-triols
and chiral 1/2,3-triacetates were measured by HPLC spectroscopy using chiral Daicel HPLC Column OD-H,
but absolute configurations were not determined.
The proposed mechanism for the one-pot synthesis of chiral 1/2,3-triols from racemic allylic hydroperox-
ides in the presence of cat. OsO4 and chiral ligands is summarized in Scheme 2.
According to the mechanism, chiral complex was obtained with the chiral ligand and osmium tetraoxide
(OsO4) in the reaction media. The chiral osmate ester B was also obtained by dihydroxylation reaction of
allylic hydoperoxide A and the chiral ligand. Then the oxidized intermediate C and L*.OsO3 were formed by
the hydrolysis of chiral osmate ester B. By transferring one oxygen atom from hydroperoxide in C structure to
OsO3 , chiral 1/2,3-triol D was obtained with an applicable enantioselectivity rate, and then osmium tetroxide,
which is recreated to sustain the next catalytic cycle, was used and applied as a practically and efficiently
reagent.
3. Experimental
3.1. General procedure-I for the synthesis of the allylic hydroperoxides22−32
First 10 mmol of olefin and TPP (5–10 mg) was dissolved in CH2 Cl2 . The solution was placed in a jacketed
glass balloon and irradiated using a tungsten lamp (500 W) with air bubbling (oxygen gas) at room temperature.
The photooxygenation reaction was monitored by TLC. Most of the reactions were completed over the time
period of 8–24 h. The solvent (CH2 Cl2) was evaporated at 20 ◦ C and 20 mmHg at the end of the reaction.
The residue was separated by (silica gel) thin layered chromatography (TLC) with hexane:methylene chloride.
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Scheme 2. The suggested mechanism for the synthesis of asymmetric 1/2,3-triols from the racemic allylic hydroperox-
ides.
3.2. General procedure-II for the synthesis of the chiral 1/2,3-triols
In a typical synthesis of the 1/2,3- triols, OsO4 (1.7 mg in 1 mL of acetone, 2.65 mg, 0.4 mol %) and chiral ligand
(0.4 mol %) were reacted at 0 ◦ C and stirred for 10 min. In another container, 2.6 mmol of allylic hydroperoxide
was dissolved in the acetone/H2 O (v/v: 4/1) mixture at 0 ◦ C. After that, the allylic hydroperoxide solution was
added slowly to the chiral ligand/OsO4 mixture solution at 0 ◦ C. The reaction continued under vigorous stirring
at 0 ◦ C for 60 min. The progress of the catalytic reaction was monitored by TLC.Then the solvent was removed
by using a rotary evaporator. Finally, the crude residue was directly purified by column chromatography on
silica gel using EtOAc-hexane as the eluent to separate the synthesized asymmetric 1/2,3-triols. The 1/2,3-triols
were determined by 1 H NMR and 13 C NMR spectra taken in D2 O or CDCl3 . For further characterization,
the triols 3a, 3b, 3c, 3d, and 3e were converted into the corresponding chiral triacetates 3aa, 3bb, 3cc, 3dd,
and 3ee, respectively, and the triacetates were prepared as in the literature.22 The chiral triols 3f and 3g
and chiral acetate derivatives 3aa, 3bb, 3cc, 3dd, and 3ee were also determined by HPLC with a Chiralcel
AS column (see supporting materials). Both the NMR and IR spectra of racemic molecules (see supporting
materials) were exactly the same in the literature.22,23 The chiral 1/2,3-triols and chiral 1/2,3-triacetates were
identified by HPLC spectroscopy (chiral Daicel HPLC Column OD-H).
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Racem-allylic hydroperoxide molecules:
rac-3-hydroperoxycyclopent-1-ene (2a), rac-3-hydroperoxycyclohex-1-ene (2b), rac-3-hydroperoxy-7-oxa-
bicyclo[4.1.0]hept-4-ene (2c), rac-3-hydroperoxy- cyclohept-1-ene (2d), rac-3-hydroperoxycyclooct-1-ene (2e),
rac-3-hydroperoxy-2,3-dimethylbut-1-ene (2f), rac-3-hydroperoxybut-1-ene (2g).
Chiral triacetates molecules:
Cyclopentane-1/2,3-triacetate (3aa). It was prepared according to general procedure II. The ee was
determined to be 46% using HPLC analysis on a Chiralcel AS column (hexane/2-propanol 90:10, 0.6 mL/min,
λ = 227 nm). Retention times were 18.2 (minor) and 20.5 (major). [α]2D5 = –47 (c 0.5, MeOH).
Cyclohexane-1/2,3- triacetate (3bb). It was prepared according to general procedure II. The ee was
determined to be 25% using HPLC analysis on a Chiralcel AS column (hexane/2-propanol 90:10, 0.6 mL/min,
λ = 227 nm). Retention times were 12.6 (major) and 15.1 (minor). [α]2D5 = +10 (c 0.5, MeOH).
7-Oxabicyclo[4.1.0]heptane-2/3,4- triacetate (3cc). It was prepared according to general proce-
dure II. The ee was determined to be 41% using HPLC analysis on a Chiralcel AS column (hexane/2-propanol
90:10, 0.6 mL/min, λ = 227 nm). Retention times were 15.9 (minor) and 17.5 (major). [α]2D5 = –2 (c 0.5,
MeOH).
Cycloheptane-1/2,3-t triacetate (3dd). It was prepared according to general procedure II. The
ee was determined to be 35% using HPLC analysis on a Chiralcel AS column (hexane/2-propanol 90:10, 0.6
mL/min, λ = 227 nm). Retention times were 17.9 (major) and 20.1 (minor). [α]2D5 = +5 (c 0.5, MeOH).
Cyclooctane-1/2,3- triacetate (3ee). It was prepared according to general procedure II. The ee was
determined to be 99% using HPLC analysis on a Chiralcel AS column (hexane/2-propanol 90:10, 0.6 mL/min,
λ = 227 nm). Retention times were 13.7 (minor) and 15.3 (major). [α]2D5 = –7 (c 0.5, MeOH).
Chiral triols molecules:
2,3-Dimethylbutane-1,2,3-triol (3f). It was prepared according to general procedure II. The ee was
determined to be 99% using HPLC analysis on a Chiralcel AS column (hexane/2-propanol 90:10, 0.6 mL/min,
λ = 227 nm). Retention times were 10.5 (major) and 12.8 (minor). [α]2D5 = +28 (c 0.5, MeOH).
Butane-1,2,3-triol (3g). It was prepared according to general procedure II. The ee was determined to
be 99% using HPLC analysis on a Chiralcel AS column (hexane/2-propanol 90:10, 0.6 mL/min, λ = 227 nm).
Retention times were 13.5 (major) and 14.8 (minor). [α]2D5 = +25 (c 0.5, MeOH).
4. Conclusion
The present study reports a new method for the synthesis of asymmetric triols from racemic allylic hydroper-
oxides in the absence of a co-oxidant and in the presence of chiral ligand and cat. OsO4 . We assumed that
the chiral ligand and cat. OsO4 were created as the chiral complex in reaction media and so this formation
can be likened to chiral ligand/cat. OsO4 in a Sharpless asymmetric dihydroxylation reaction. The synthesis
of asymmetric 1/2,3-triols was carried out by the catalytic cycle of chiral ligand and cat. OsO4 . Later, the
reaction process continues similarly to the dihydroxilation reaction formed by the cat. OsO4 /NMO system.
This method provides many advantages such as one-pot synthesis, absence of a co-oxidant, catalytic oxidation,
and being practical and economic; moreover it ensures the high yielded synthesis of asymmetric triols with
considerable enantioselectivity under very mild conditions. Synthesized triols using the new method can be
employed as starting materials for the synthesis of most natural products. The new catalytic chiral system for
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the synthesis of chiral 1/2,3-triols is thought to be a good candidate to be used in synthetic organic chemistry
owing to its chirality, effectiveness, and simplicity. Further applications of this method for the synthesis of
asymmetric triols are in progress and the improvements will be reported.
Acknowledgment
¨
This study was supported partially by the Scientific and Technological Research Council of Turkey (TUBITAK)
˙
(Project No: 109T815).
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834

Supporting Information
HPLC and IR spectra and spectral data for the chiral triol or triacetate compounds
HPLC analysis: Chiralcel AS, mobile phase: 10% iPrOH/hexane (1/9), flow rate: 0.6
mL/min, 227 nm, retention time: t1 = 10.5 min, t2 = 12.8 min. Enantiomeric excess (ee):
99%. [ꢀ]ꢀꢀꢁ= +28 (c 0.5, MeOH).
IR (KBr, cm–1): 3390.9, 2980.6, 1381.8, 1041.3.
2,3-Dimethylbutane-
1,2,3-triol (3f)
111.6
110
108
106
104
102
100
98
425.97
1717.48
2935.57
96
%T
832.17
888.10
1465.42
94
601.13
2980.58
92
1172.02
90
949.11
1381.84
88
1102.09
1131.47
3390.98
86
84
1041.26
82
80.8
4000.0
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400.0
cm-1
1

i
HPLC analysis: Chiralcel AS, mobile phase: 10% PrOH/hexane (1/9), flow rate: 0.6
mL/min, 227 nm, retention time: t1 = 13.5 min, t2 = 14.8 min., Enantiomeric excess (ee):
89%. [ꢀ]ꢀꢀꢁ= +25 (c 0.5, MeOH).
IR (KBr, cm–1): 3708.2, 2991.6, 1494.7, 1187.9.
Butane-1,2,3-triol
(3g)
119,6
119
118
117
116
115
114
113
112
111
110
109
108
107
3708,18
1275,52
1236,36
1426,57
3114,84
600,69
3036,41
2991,59
%T
1563,63
2868,34
684,74
1227,97
1187,88
1711,88
1370,62
1381,81 1311,16
1521,67
1494,69
1057,34
1443,35
2319,32
1860,51
1009,79
950,74
811,18
900,69
881,11
836,36
105,9
4000,0
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400,0
cm-1
2

i
HPLC analysis: Chiralcel AS, mobile phase: 10% PrOH/hexane (1/9), flow rate: 0.6
mL/min, 227 nm, retention time: t1 = 17.9 min, t2 = 19.9 min., Enantiomeric excess (ee):
46%. [ꢀ]ꢀꢀꢁ= –47 (c 0.5, MeOH).
IR(KBr, cm–1): 2941.5, 1743.7, 1372.9, 1234.7.
3aa
124.3
120
483.53
3470.26
115
110
105
100
95
605.30
2851.54
1644.75
2941.50
897.90
1435.74
%T
90
85
80
75
70
958.78
1144.05
1372.96
1046.55
1743.72
1234.74
65
61.0
4000.0
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400.0
cm-1
3

i
HPLC analysis: Chiralcel AS, mobile phase: 10% PrOH/hexane (10/90), flow rate: 0.6
mL/min, 227 nm, retention time: t1 = 12.6 min, t2 = 15.0 min. Enantiomeric excess (ee):
25%. [ꢀ]ꢀꢀꢁ= +10 (c 0.5, MeOH). IR (KBr, cm–1): 2925.2, 1743.0, 1371.4, 1234.2.
3bb
105.4
104
103
102
101
100
99
688.11
2845.93
2925.16
637.76
601.39
836.36
1429.37
1124.47
1104.89
948.25
98
1371.37
1054.83
97
%T
96
95
94
93
92
91
1743.02
1234.16
90
89
88.3
4000.0
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400.0
cm-1
4

i
HPLC analysis: Chiralcel AS, mobile phase: 10% PrOH/hexane (10/90), flow rate: 0.6
mL/min, 227 nm, retention time: t1 = 18.0 min, t2 = 20.3 min. Enantiomeric excess (ee):
35%. [ꢀ]ꢀꢀꢁ= +5 (c 0.5, MeOH). IR (KBr, cm–1): 2938.9, 1742.9, 1370.4, 1231.7.
3dd
130,2
1097,17
125
120
115
110
105
100
95
3462,12
802,67
892,30
477,50
1560,83
603,05
1438,92
2869,20
931,46
978,17
959,44
1141,25
2938,94
%T
1370,43
1030,49
90
85
80
1231,74
75
1742,97
69,8
4000,0
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400,0
cm-1
5

i
HPLC analysis: Chiralcel AS, mobile phase: 10% PrOH/hexane (10/90), flow rate: 0.6
mL/min, 227 nm, retention time: t1 = 13.7 min., t2 = 15.1 min. Enantiomeric excess (ee):
90%. [ꢀ]ꢀꢀꢁ= –7 (c 0.5, MeOH). IR (KBr, cm–1): 2929.8, 1735.1, 1371.1, 1242.4
3ee
107.8
107
106
105
104
103
102
101
3019.60
1096.50
1132.86
1448.95
2851.54
1371.15
1030.74
%T
2929.78
100
99
98
97
96
95
1735.09
1242.44
94
93.4
4000.0
3600
3200
2800
2400
2000
1800
1600
1400
1200
1000
800
600
400.0
cm-1
6

i
HPLC analysis: Chiralcel AS, mobile phase: 10% PrOH/hexane (10/90), flow rate: 0.6
mL/min, 227 nm, retention time: t1 = 15.9 min, t2 = 17.5 min. Enantiomeric excess (ee):
41%. [ꢀ]ꢀꢀꢁ= –2 (c 0.5, MeOH). IR (KBr, cm–1): 2931.5, 1743.9, 1367.1, 1223.3, 1034.9.
3cc
98,6
96
94
92
90
88
86
84
82
80
78
76
74
72
70
3473,70
818,19
525,47
414,66
2851,54
604,41
2931,50
789,08
758,98
887,07
942,78
1434,90
1127,90
%T
983,31
1071,32
1367,15
1034,98
1743,78
68
1223,34
1400
66,5
4000,0
3600
3200
2800
2400
2000
1800
1600
1200
1000
800
600
400,0
cm-1
7