2-{(4a′S,6a′S,10a′R,10b′R)-Octahydrospiro[1,3-dioxolane-2,2′-pyrano[2,3-c]chromen]-6a′(1′H)-yloxy}ethanol in the Synthesis of (2S)- and (2R)-Dodecane-1,2-diols

Article abstract of DOI:10.1134/S1070428020100279

Abstract: Michael adduct of levoglucosenone and cyclohexanone, 1,6-anhydro-3,4-dideoxy-4-C-(2-oxocyclohexan-1-yl)-β-D-erythrohexo-2-ulose, was treated with ethylene glycol in the presence of oxalic acid, and the resulting mixed ketal, 2-{(4a′S,6a′S,10a′R,10b′R)-octahydrospiro[1,3-dioxolane-2,2′-pyrano[2,3-c]chromen]-6a′(1′H)-yloxy}ethanol, was used a chiral auxiliary in the synthesis of vicinal diols.

Full text of DOI:10.1134/S1070428020100279

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 10, pp. 1840–1843. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 10, pp. 1611–1615.
SHORT
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2-{(4a′S,6a′S,10a′R,10b′R)-Octahydrospiro[1,3-dioxolane-
2,2′-pyrano[2,3-c]chromen]-6a′(1′H)-yloxy}ethanol
in the Synthesis of (2S)- and (2R)-Dodecane-1,2-diols
L. Kh. Faizullinaa,*, A. R. Tagirova, Sh. M. Salikhova, S. F. Petrovaa, and F. A. Valeeva
a Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, Ufa, 450054 Russia
*e-mail: sinvmet@anrb.ru
Received May 19, 2020; revised May 28, 2020; accepted June 3, 2020
Abstract—Michael adduct of levoglucosenone and cyclohexanone, 1,6-anhydro-3,4-dideoxy-4-C-(2-oxocyclo-
hexan-1-yl)-β-D-erythrohexo-2-ulose, was treated with ethylene glycol in the presence of oxalic acid, and the
resulting mixed ketal, 2-{(4a′S,6a′S,10a′R,10b′R)-octahydrospiro[1,3-dioxolane-2,2′-pyrano[2,3-c]chromen]-
6a′(1′H)-yloxy}ethanol, was used a chiral auxiliary in the synthesis of vicinal diols.
Keywords: chiral inductor, levoglucosenone, Michael adduct, mixed ketal, vicinal diols
DOI: 10.1134/S1070428020100279
We previously reported that mixed ketal 2 can be
used as a chiral auxiliary in the synthesis of optically
active vicinal diols [1, 2]. In continuation of these
studies, with the goal of finding diastereoisomers with
a larger difference in chromatographic mobilities,
aldehyde 3 [2] was alkylated with decylmagnesium
bromide. In fact, the resulting diastereoisomers 4a and
4b (Scheme 1) can be readily separated by silica gel
chromatography (∆Rf = 0.2) and were isolated in the
pure state in 49 and 36% yield, respectively. The
formation of diastereoisomers 4a and 4b was con-
1′-H/C6a and 1′-H/C2′ correlations were observed in
their HMBC spectra.
The hydrolysis of 4a in MeOH–HCl–THF gave
three products (Scheme 2): hemiketal 5, (2R)-diol 6a,
and mixed ketal 7 in 87, 30, and 2% yield, respectively.
(2S)-Diol 6b and compounds 5 and 7 were obtained by
hydrolysis of diastereoisomer 4b. To eliminate ambi-
guity in the results, a racemic mixture of dodecane-1,2-
diols 6a and 6b was separated using a Nucleosil
Chiral-1 column; we thus isolated pure enantiomers
with [α]2D0 = +11° and –11° (c = 2.5, EtOH) ([α]2D0
±13°, c = 2.5, EtOH [3]).
=
13
firmed by the C NMR spectra which showed signals
for C2′ at δC 70.58 and 70.74 ppm and for C1′ at
δC 63.43 and 63.72 ppm, respectively. In addition,
The hydrolysis of 4a and 4b in acetone in the pres-
ence of a catalytic amount of pyridinium p-toluenesul-
Scheme 1.
H
H
O
O
O
O
O
O
HO
O
O
O
O
[1, 2]
[2]
H
H
O
O
H
O
O
O
H
H
H
1
2
3
OH
OH
H
H
O
O
O
O
C10H21
C10H21
2'
C10H21MgBr
85%
O
O
H
H
O
O
1'
+
6a
O
O
H
H
4a
4b
1840

2-{(4a′S,6a′S,10a′R,10b′R)-OCTAHYDROSPIRO[1,3-DIOXOLANE-...
1841
Scheme 2.
CH2
H
O
H
O
O
O
OH
HO
O
H
H
O
O
4a, 4b
+
+
Me
OH
(see Table 1)
( )9
O
O
H
H
5
6a, 6b
7
fonate (PPTS) (Table 1) gave the corresponding aceto-
nides with [α]2D0 = +31.8° and –41.5° (c = 0.67 M,
CHCl3), and the final hydrolysis of these acetonides in
Ac2O–H2O afforded enantiomers 6a and 6b with
[α]2D0 = +4° and –13°, respectively (c = 1.3 M, EtOH).
2,2′-pyrano[2,3-c]chromene) (7) were described
previously [2].
1-{(4a′S,6a′S,10a′R,10b′R)-Octahydrospiro-
[1,3-dioxolan-2,2′-pyrano[2,3-c]chromen]-6a′(1′H)-
yloxy}dodecan-2-ols (4a/4b). Aldehyde 3, 0.42 g
(1.35 mmol), was dissolved in 7.0 mL of THF, 0.5 mL
(1.91 mmol) of a solution of decylmagniesium bromide
in diethyl ether was added with stirring, and the mix-
ture was stirred for 15 min (TLC), treated with 1.0 mL
of a saturated aqueous solution of ammonium chloride,
and extracted with ethyl acetate (2×5.0 mL). The
extract was dried over magnesium sulfate, the solvent
was distilled off, and the residue was subjected to silica
gel column chromatography to isolate 0.25 g (54%) of
an oily mixture of 4a and 4b at a ratio of 1:1.6; Rf 0.2
(CHCl3–i-PrOH, 50:1). [α]D20 = –57° (4a), 43° (4b)
(c = 1.0, CHCl3). 1H NMR spectrum (CDCl3), δ, ppm:
4a: 0.82–0.87 m (3H, CH3), 1.12–1.32 m (24H, 1-H,
10a-H, 8-H, 10-H, 9-H, 7-H, 3′-H, 4′-H, 5′-H, 6′-H,
7′-H, 8′-H, 9′-H, 10′-H, 11′-H), 1.38–1.48 m (2H, 3′-H,
9-H), 1.52–1.61 m (1H, 10-H), 1.68–1.75 m (1H, 7-H),
1.88–1.92 m (1H, 10b-H), 1.93–2.05 m (1H, 1-H),
2.30 br.s (1H, OH), 3.07–3.14 m (1H, 4a-H), 3.27–
3.32 m (1H, 1′-H), 3.36–3.40 m (1H, 3-H), 3.52 t (1H,
In order to improve the yield of vicinal diols, the
hydrolysis of a mixture of 4a and 4b was carried out
using CeCl3·7H2O in the presence of sodium iodide in
acetonitrile and aqueous acetic acid (Table 1). The
yield of epimeric (2RS)-diols 6a and 6b was increased
to 88% when the hydrolysis was performed in aqueous
acetic acid.
In summary, we have demonstrated the possibility
of using mixed ketal obtained in one step from the
Michael adduct of levoglucosenone and cyclohexanone
as a chiral inductor in the synthesis of optically active
vicinal diols. Optimal conditions have been found
(AcOH, H2O, 80°C) for the hydrolysis of diastereo-
isomeric ketals 4a and 4b to afford chiral vicinal diols
6a and 6b in 88% yield.
2-{(4a′S,6a′S,10a′R,10b′R)-Octahydrospiro[1,3-
dioxolane-2,2′-pyrano[2,3-c]chromen]-6a′(1′H)-
yloxy}ethanol (2), 2-{(4a′S,6a′S,10a′R,10b′R)-octa-
hydrospiro[1,3-dioxolane-2,2′-pyrano[2,3-c]chromen]-
6a′(1′H)-yloxy}ethanal (3), (4a′S,6a′S,10a′R,10b′R)-
octahydro-3′H-spiro[1,3-dioxolane-2,2′-pyrano[2,3-c]-
chromen]-6a′(1′H)-ol (5), and (4a′S,6a′S,10a′R,10b′R)-
6a′-(prop-2-en-1-yloxy)decahydrospiro[1,3-dioxolane-
2
3
5-HB, J = 10.5, J5B,4a = 5.3 Hz), 3.62–3.69 m (3H,
1′-H, 5-HA, 3-H), 3.77–3.83 m (1H, 2′-H), 3.89–4.05 m
(4H, 1″-H, 2″-H); 4b: 0.83–0.88 m (3H, CH3), 1.17–
1.33 m (24H, 1-H, 10a-H, 8-H, 10-H, 9-H, 7-H, 3′-H,
4′-H, 5′-H, 6′-H, 7′-H, 8′-H, 9′-H, 10′-H, 11′-H), 1.42–
Table 1. Hydrolysis of diastereoisomers 4a and 4b
Yield, %
Reagents
5
6a, 6b
7
87a
30
28
2
2
MeOH–HCl–THF
47b
(1) Acetone, PPTS
(2) Ac2O–H2O
62
60
47
36
15
15
CeCl3·7H2O, NaI, MeCN
AcOH, H2O
67
65
53
88
12
22
a From 4a.
b From 4b.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

FAIZULLINA et al.
1842
1.48 m (2H, 3′-H, 9-H), 1.52–1.61 m (1H, 10-H), 1.70–
1.73 m (1H, 7-H), 1.8–1.95 m (1H, 10b-H), 1.98–
2.02 m (1H, 1-H), 2.29 br.s (1H, OH), 3.10–3.15 m
(1H, 4a-H), 3.25–3.27 m (1H, 1′-H), 3.28–3.30 m (1H,
mixture was treated with a saturated aqueous solution
of sodium hydrogen carbonate and extracted with ethyl
acetate (3×5.0 mL), the extract was dried over MgSO4,
the solvent was distilled off, and the residue was sub-
jected to silica gel column chromatography to isolate
0.015 g (65%) of 5, 0.006 g (22%) of 7, and 0.015 g
(88%) of 6a/6b.
2
3-H), 3.31–3.35 m (1H, 1′-H), 3.60 t (1H, 5-HB, J =
3
10.4, J5B,4a = 5.5 Hz), 3.65–3.69 m (2H, 5-HA, 3-H),
3.72–3.78 m (1H, 2′-H), 3.91–4.07 m (4H, 1″-H,
2″-H). 13C NMR spectrum (CDCl3), δC, ppm: 4a: 14.06
(CH3), 22.11 (C9), 22.62 (C11′), 24.59 (C8), 25.22
(C10′), 25.50 (C9), 29.27 (C5′), 29.50 (C6′), 29.54 (C7′),
31.84 (C4′), 32.00 (C7), 33.01 (C3′), 36.07 (C10b), 36.10
(C1), 47.60 (C10a), 62.57 (C5), 63.43 (C1′), 63.57 (C1″),
64.59 (C2″), 70.58 (C2′), 71.12 (C3), 76.75 (C4a), 97.97
(C6a), 105.05 (C2); 4b: 14.11 (CH3), 22.32 (C9), 22.68
(C11′), 24.51 (C8), 25.35 (C10′), 25.56 (C9), 29.33 (C5′),
29.61 (C6′), 29.67 (C7′), 31.91 (C4′), 32.18 (C7), 33.64
(C3′), 36.12 (C10b), 36.21 (C1), 47.83 (C10a), 62.69 (C5),
63.72 (C1′), 64.61 (C1″), 64.84 (C2″), 70.74 (C2′), 71.13
(C3), 77.13 (C4a), 97.96 (C6a), 105.12 (C2). Found, %:
C 68.71; H 10.17. C26H46O6. Calculated, %: C 68.69;
H 10.20.
c. A catalytic amount of pyridinium p-toluenesul-
fonate was added to a solution of 0.1 g (0.22 mmol) of
compound 4a in 4 mL of acetone, and the mixture was
stirred until the reaction was complete (TLC). The
mixture was treated with water and extracted with ethyl
acetate (3×5.0 mL), the extract was dried over MgSO4,
the solvent was distilled off, and the dry residue
was treated with a mixture of acetic acid and water
(3.0:1.5 mL). After completion of the reaction (TLC),
the mixture was treated with a saturated solution of
sodium hydrogen carbonate and extracted with ethyl
acetate (3×5.0 mL), the extract was dried over MgSO4
and evaporated, and the residue was subjected to
chromatography to isolate 0.002 g (15%) of 7, 0.029 g
(62%) of 5, and 0.026 g (47%) of diol 6a.
(2R)- and (2S)-Dodecane-1,2-diols 6a and 6b.
Ketal 4a or 4b, 0.23 g (0.47 mmol), was dissolved in
methanol, 30% aqueous HCl was added, and the mix-
ture was stirred until the initial compound disappeared
(TLC). The mixture was treated with a saturated aque-
ous solution of sodium hydrogen carbonate and ex-
tracted with ethyl acetate (3×10.0 mL), the extract was
dried over MgSO4, the solvent was distilled off, and
the products were isolated by silica gel column chro-
matography. From ketal 4a we obtained 0.08 g (87%)
of 5, 0.01 g (2%) of 7, and 0.03 g (30%) of (2R)-diol
6a; from ketal 4b we obtained 0.08 g (47%) of 5,
0.01 g (2%) of 7, and 0.03 g (28%) of (2S)-diol 6b.
Physicochemical characteristics of diols 6a and 6b
(C12H26O2) were consistent with published data [3].
Likewise, by hydrolysis of 0.08 g (0.17 mmol) of
4b we obtained 0.002 g (15%) of 7, 0.024 g (60%) of
5, and 0.023 (36%) of 6b.
1
The H and 13C NMR spectra were recorded on
a Bruker Avance III spectrometer (Germany) at
1
500 MHz for H. Analytical TLC was performed on
Sorbfil PTSKh-AF-A plates (Sorbpolimer, Krasnodar,
Russia). The melting points were measured with
a Boetius PHMK 05 melting point apparatus
(Germany). Elemental analyses were carried out using
a Euro 3000 CHNS(O) analyzer (Italy). The optical
rotations were measured on a Perkin Elmer 341 polar-
imeter (USA). The solvents used were purified
according to standard procedures [4–6]. Pyridinium
p-toluenesulfonate (99%) was purchased from Sigma–
Aldrich.
Hydrolysis of ketals 4a and 4b. a. A mixture of
ketals 4a and 4b, 0.05 g (0.01 mmol), was dissolved in
7.0 mL of acetonitrile, 0.06 g (0.16 mmol) of CeCl3·
7H2O and 0.002 g (0.02 mmol) of NaI were added, and
the mixture was stirred until the initial compounds
disappeared (TLC). The mixture was treated with
a saturated aqueous solution of Na2S2O3 and extracted
with ethyl acetate (3×10.0 mL), the extract was dried
over MgSO4, the solvent was distilled off, and the
residue was subjected to silica gel column chromatog-
raphy to isolate 0.02 g (67 %) of 5, 0.004 g (12%) of 7,
and 0.02 g (53%) of 6a/6b.
ACKNOWLEDGMENTS
The authors thank Circa Group for providing levo-
glucosenone. The spectral and analytical studies were
performed using the equipment of the Chemistry joint center
(Ufa Institute of Chemistry, Russian Academy of Sciences)
and Agidel regional joint center (Ufa Federal Research
Center, Russian Academy of Sciences).
FUNDING
b. A solution of 0.04 g (0.01 mmol) of 4a/4b in
7.0 mL of 70% aqueous acetic acid was stirred at 80°C
until the initial compounds disappeared (TLC). The
This study was performed in the framework of state
assignment no. AAAA-A20-120012090028-3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 10 2020

2-{(4a′S,6a′S,10a′R,10b′R)-OCTAHYDROSPIRO[1,3-DIOXOLANE-...
1843
3. Júnior, C.O., le Hyaric, M., Costa, C.F., Corrêa, T.A.,
Taveira, A.F., Araújo, D.P., Reis, E.F., Lourenço, M.C.,
Vicente, F.R., and Almeida, M.V., Mem. Inst. Oswaldo
Cruz, 2009, vol. 104, p. 703.
CONFLICT OF INTEREST
The authors declare the absence of conflict of interest.
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