Preparation and stereochemistry of the isopropylidene derivatives of 1,2-dihydronaphtho[2,1-b]furan-1,2-diol and 1,2,9,10-tetrahydronaphtho[2,1-b:7, 8-b′] difuran-1,2,9,10-tetraol in comparison with the corresponding acetyl derivatives

Article abstract of DOI:10.1081/SCC-200039376

1,2-Dihydronaphtho[2,1-b]furan-1,2-diol and 1,2,9,10-tetrahydronaphtho[2,1- b:7,8-b′]difuran-1,2,9,10-tetraol were transformed into the corresponding isopropylidene derivatives, which were studied mainly by ¹H NMR and chiral HPLC analyses in terms of a possible transformation mechanism and stereochemistry in comparison with their corresponding acetyl derivatives.

Full text of DOI:10.1081/SCC-200039376

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Preparation and
Stereochemistry of the
Isopropylidene Derivatives of
1,2‐Dihydronaphtho[2,1‐b]Furan‐
and
1,2,9,10‐Tetrahydronaphtho[2,1‐b
Difuran‐1,2,9,10‐Tetraol
in Comparison with the
Corresponding Acetyl
Derivatives
a
a
Makoto Yamaye , Yoshiko Motoyanagi , Aya
a
a
Nakagawa , Sanae Kametani , Tetsutaro
b
a
b
Yoshinaga , Namiko Cho (Toh) , Xiaobo Fan
&
b
Taketoshi Kito
a
Faculty of Engineering , Kyushu Kyoritsu
University , 1‐8 Jiyugaoka, Yahatanishi,
Kitakyushu, 807‐8585, Japan
b
Department of Applied Chemistry , Kyushu
Institute of Technology , 1‐1 Sensuicho, Tobata,
Kitakyushu, Japan
Published online: 12 Jan 2011.

To cite this article: Makoto Yamaye , Yoshiko Motoyanagi , Aya Nakagawa ,
Sanae Kametani , Tetsutaro Yoshinaga , Namiko Cho (Toh) , Xiaobo
Fan & Taketoshi Kito (2004) Preparation and Stereochemistry of the
Isopropylidene Derivatives of 1,2‐Dihydronaphtho[2,1‐b]Furan‐1,2‐Diol and
1,2,9,10‐Tetrahydronaphtho[2,1‐b:7,8‐b′] Difuran‐1,2,9,10‐Tetraol in Comparison
with the Corresponding Acetyl Derivatives, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
34:23, 4313-4323, DOI: 10.1081/SCC-200039376
To link to this article: http://dx.doi.org/10.1081/SCC-200039376
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 23, pp. 4313–4323, 2004
Preparation and Stereochemistry of the
Isopropylidene Derivatives of
,2-Dihydronaphtho[2,1-b]Furan-1,2-Diol and
1
0
1,2,9,10-Tetrahydronaphtho[2,1-b:7,8-b ]
Difuran-1,2,9,10-Tetraol in Comparison with
the Corresponding Acetyl Derivatives
1
,
1
1
Makoto Yamaye, * Yoshiko Motoyanagi, Aya Nakagawa,
1
Sanae Kametani, Tetsutaro Yoshinaga, Namiko Cho (Toh),
2
1
2
Xiaobo Fan, and Taketoshi Kito
2
1
Faculty of Engineering, Kyushu Kyoritsu University, 1-8 Jiyugaoka,
Yahatanishi, Kitakyushu, Japan
2
Department of Applied Chemistry, Kyushu Institute of Technology,
1
-1 Sensuicho, Tobata, Kitakyushu, Japan
ABSTRACT
1,2-Dihydronaphtho[2,1-b]furan-1,2-diol
naphtho[2,1-b:7,8-b ]difuran-1,2,9,10-tetraol were transformed into the
and
1,2,9,10-tetrahydro-
0
corresponding isopropylidene derivatives, which were studied mainly
*
Correspondence: Makoto Yamaye, Faculty of Engineering, Kyushu Kyoritsu Univer-
sity, 1-8 Jiyugaoka, Yahatanishi, Kitakyushu 807-8585, Japan; Fax: þ81-93-603-8186;
E-mail: yamaye@kyukyo-u.ac.jp.
4
313
DOI: 10.1081/SCC-200039376
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4
314
Yamaye et al.
1
by H NMR and chiral HPLC analyses in terms of a possible transform-
ation mechanism and stereochemistry in comparison with their corre-
sponding acetyl derivatives.
Key Words: 1,2-Dihydronaphtho[2,1-b]furan-1,2-diol; 1,2,9,10-Tetra-
0
hydronaphtho[2,1-b:7,8-b ]difuran-1,2,9,10-tetraol; Isopropylidenation;
Stereochemistry; Chiral HPLC.
INTRODUCTION
During our study on a series of heteroaromatic compounds containing
1–4]
[
the 2,8-dioxabicyclo[3.3.0]octane ring system,
their precursors 1,2-dihydronaphtho[2,1-b]furan-1,2-diol (1) and 1,2,9,10-
we have isolated as
0
tetrahydronaphtho[2,1-b:7,8-b ]difuran-1,2,9,10-tetraol (2), both of which
carry vicinal OH groups, one being hemiacetal and the other alcoholic.
Theoretically, diol 1 possesses four stereoisomers (cis and trans forms,
and their mirror images) with respect to the orientation of the two OH
groups located at the C1 and C2 atoms (Fig. 1).
As for tetraol 2 (Fig. 2), which possesses the symmetrical nature of
naphthalene framework, 10 stereoisomers, among 16 in principle, are possible
with respect to the orientation of the four OH groups at the C1, C2, C9, and
C10 atoms. Of these, four stereoisomers have their mirror images, and there-
fore, we will take the following six isomers into consideration: cis-anti-cis, cis-
syn-cis, cis-anti-trans, cis-syn-trans, trans-anti-trans, and trans-syn-trans. For
naming, the cis-anti-cis, for example, designates that the two OH groups at the
C1 and C2 atoms are cis to each other and the other two at the C9 and C10
atoms cis, together with the two OH groups at the C1 and C10 atoms in
anti orientation.
We are interested in the stereochemistry of these compounds for their
[5]
possible use as synthetic precursors, metal-ion scavengers, and so forth.
Figure 1. Four stereoisomers of diol 1.

Isopropylidenation of Diol 1 and Tetraol 2
4315
Figure 2. Tetraol 2.
To facilitate structural characterization, both 1 and 2 were converted into the
[2]
corresponding isopropylidene and acetyl derivatives. In particular, the iso-
propylidene derivatives of 1 and 2, forming acetone bridges between their
vicinal OH groups in the cis manner, will simplify their stereochemistry.
RESULTS AND DISCUSSION
[2]
An acid-catalyzed isopropylidenation of diol 1 (consisted of the
cis/trans ratio of 15/85–30/70 depending on the reaction conditions) was
conducted in dry acetone in the presence of anhydrous CuSO at room
4
temperature to give the corresponding isopropylidene derivatives (3) in an
[
6]
excellent yield (98%). The observation indicates that 1 underwent isomeri-
zation of the trans into the cis form. A possible transformation pathway invol-
ving the alcoholic and hemiacetal OH groups is shown in Scheme 1. Because
the isopropylidenation competed with lactonization, the former procedure,
without using anhydrous CuSO , dominantly formed the corresponding
4
lactone (4), with 3 as a minor product (,20% yields).
Treatment of tetraol 2 in dry acetone was also carried out in the presence
of anhydrous CuSO . The resulting diisopropylidene derivatives 5 can poss-
4
ibly exist only in two forms, the cis-anti-cis and cis-syn-cis forms, naming
being done in a similar manner as for 2. However, a single peak (rather
than two peaks) on high-performance liquid chromatography (HPLC) with
an octadecyl silica (ODS) column was observed for a crude product 5, indicat-
ing that the peak be assigned to either of the two isomers (Fig. 3). Common
spectroscopic methods, including ultraviolet (UV), infrared (IR), nuclear mag-
netic resonance (NMR), and mass spectrometry (MS), were unable to deter-
mine either the anti or syn configuration of 5.
Assignment of stereochemistry to this single peak was done by HPLC
using a chiral, because the cis-anti-cis isomer is present as a racemate but
the cis-syn-cis isomer is not. A pair of peaks at the retention time of 9 and
13 min with equal intensity were observed by UV detection at 240 nm and
the corresponding minus and plus peaks appeared with equal intensity by

4
316
Yamaye et al.
Scheme 1. A possible transformation mechanism.
the optical rotation (OR) detector (Fig. 4). The results clearly show that this
single peak corresponds to the cis-anti-cis isomer that consists of a pair of
enantiomers.
Judging from the inspection of molecular models, failure in detection of
the other cis-syn-cis isomer was somewhat unexpected.
Figure 3. Diisopropylidene derivatives 5.

Isopropylidenation of Diol 1 and Tetraol 2
4317
Figure 4. Chiral HPLC of diisopropylidene derivative 5.
1
As previously reported for diol 1, HPLC and H NMR studies showed that
the cis/trans ratio of the diacetyl derivatives of 1 roughly agreed with that of
[
2]
the starting diol 1 (cis/trans ¼ 30/70). In contrast to diol 1, tetraol 2 pro-
1
vided a rather complicated H NMR spectrum so that exact assignment of
each signal was difficult. Therefore, we have reexamined acetylation of
[7]
tetraol 2, producing the corresponding tetraacetyl derivatives (6), which
were subjected to HPLC analysis.
HPLC measurement revealed that the tetraacetyl derivatives consisted of
three main peaks, 6a, 6b, and 6c, with the area ratio of 50 : 30 : 20, respect-
ively. We were able to isolate these stereoisomers by simple recrystallization
1
and studied their stereochemistry by H NMR spectroscopy, with the help of
nuclear Overhauser effect (NOE) technique and chiral HPLC measurement.
1
For each of these three isomers in their H NMR spectra, only one pair of
proton signals was detected for the two pairs of hydrogen groups, H1-H2
and H9-H10, indicating that 6a, 6b, and 6c are all symmetrical in structure.
Therefore, each of these three stereoisomers was suggested to possess one
of the four possible structures, trans-anti-trans, trans-syn-trans, cis-anti-cis,
and cis-syn-cis.
NOE measurement was done to discriminate the trans from the cis
isomers. Irradiation of the proton signal corresponding to the H2 (or H9)
atom of 6a and 6b did not cause any enhancement of the one corresponding

4
318
Yamaye et al.
to the H1 (or H10) atom. We speculate that the H1 (or H10) and H2 (or H9)
atoms are far apart from each other. Accordingly, we conclude that both tetra-
acetyl isomers 6a and 6b are trans in configuration (Figs. 5 and 6). Irradiation
of the H2 proton signal (6.17 ppm) of 6c did not enhance the H1 signal
(
5.50 ppm), indicating that the cis configuration is assigned to 6c (Fig. 7).
Finally, comparison of the magnitude of the H1 (or H10) chemical shift was
made among 6a, 6b, and 6c. The chemical shift (5.50 ppm) of 6c was at the
highest field, coinciding with the fact that the H1 (or H10) proton of 6c was
upfield shifted by the acetoxyl group located at the C10 (or C1) atom. We
conclude that 6c possesses the anti form.
Assignment of the anti-syn configuration to 6a and 6b was performed by
means of chiral HPLC using a Chiralcel OD-H column. Thus, the configur-
ation was determined anti for 6a and syn for 6b, because enantiomers were
present for 6a but not for 6b (Fig. 8).
Accordingly, in the acetylation of diol 2, we conclude that tetraacetyl
derivatives 6a, 6b, and 6c possess the trans-anti-trans, trans-syn-trans, and
cis-anti-cis configuration, respectively, and that the formation ratio of
6a : 6b : 6c ¼ 50 : 30 : 20 may qualitatively reflect their stability. However,
we cannot conclude that this isomer ratio agrees to that of the starting
tetraol 2 isomers, as in the case of diol 1 isomers and the corresponding dia-
cetyl derivatives.
[2]
In summary, an acid-catalyzed isopropylidenation of tetraol 2 in the
presence of anhydrous CuSO solely led to formation of the cis-anti-cis
4
1
Figure 5. H NMR of 6a: trans-anti-trans.

Isopropylidenation of Diol 1 and Tetraol 2
4319
1
Figure 6. H NMR of 6b: trans-syn-trans.
isomer of its diisopropylidene derivatives 5. No cis-syn-cis isomer of 5 was
detected, presumably due to electronic repulsion between the two O atoms
located at the C1 and C10 atoms. Because of similar reasoning, we conclude
that the cis-syn-cis isomer was not formed for the tetraacetyl derivatives of
tetraol 2.
1
Figure 7. H NMR of 6c: cis-anti-cis.

4
320
Yamaye et al.
Figure 8. Tetraacetyl derivatives 6a and 6b.
EXPERIMENTAL SECTION
All reagents were of commercial grade. Melting points were determined
on a Yanaco MP-500D and are uncorrected. IR spectra were recorded on a
Jasco FT/IR-230 spectrophotometer in KBr pellets. UV-visible spectra
were measured on a Perkin Elmer Lambda 20 spectrophotometer at room
1
13
temperature. H NMR and C NMR spectra were obtained on a JNM-
AL400 spectrometer. Chemical shifts are expressed in ppm relative to
Me Si as internal standard. Mass spectra (MS) were obtained on a Joel
4
JMS-SX102A. Microanalyses were carried out on a Yanaco CHN corder
MT-5. HPLC analysis was performed on a Jasco HPLC chromatograph
(
column (Jasco CrestPak C18T-5) and MeOH-H O (80 : 20) as the mobile
Gulliver series) with a UV detector operating at 240 nm using an ODS
2
phase. Chiral chromatography was performed using a Daicel Chiralcel
OD-H column with n-hexane-2-propanol (80 : 20) at room temperature and
with UV (240 nm) and OR detectors.
Representative examples are described.
Isopropylidene Derivative 3 from Diol 1
Diol 1 (4.5 g, 20 mmol) was dissolved in anhydrous acetone (100 mL,
1
.4 mol) with stirring for 10 min at room temperature, and then anhydrous
CuSO (4.0 g, 25 mmol) was added. Upon addition of concentrated H SO
4
4
2
(
0.2 mL) under cooling in an ice bath (,58C), the resulting mixture was
stirred at room temperature (16–188C) for 7 h, until the spot of the starting
disappeared by monitoring on TLC. The mixture was filtered to remove
CuSO and was neutralized with saturated NaHCO solution in an ice bath.
1
4
3
The addition of cold water (150 mL) caused precipitation of the crude

Isopropylidenation of Diol 1 and Tetraol 2
4321
product 3 (4.7 g, 98%). Recrystallization from MeOH gave an analytical
sample.
2
1
Mp 92.0–92.58C; IR (KBr) n 3000, 1080 cm ; UV (MeOH) lmax
1
28 nm (log 1 4.82); H NMR (400 MHz, acetone-d ) d 1.10 (s, 3H, CH ),
2
6
3
1
C H), 7.11–7.92 ppm (m, 6H, ArH); C NMR (100.4 MHz, acetone-d ) d
.47 (s, 3H, CH ), 6.15 (d, 1H, J ¼ 5.1 Hz, C H), 6.47 (d, 1H, J ¼ 5.1 Hz,
3
1
1
3
2
6
2
8.0, 28.0, 81.6, 108.8, 112.7, 113.4, 118.8, 123.2, 124.2, 128.0, 129.3,
þ
130.3, 131.3, 132.8, 157.5 ppm; MS (EI) m/z (relative intensity) 242 (M ,
7
Found: C, 74.21; H, 5.87.
8), 213 (81), 128 (100). Anal. Calcd. for C H O : C, 74.36; H, 5.82.
1
5 14 3
Diisopropylidene Derivatives 5 from Tetraol 2
Tetraol 2 (2.9 g, 10 mmol) was dissolved in anhydrous acetone (70 mL,
.95 mol) with stirring for 10 min at room temperature, and then anhydrous
0
CuSO (4.0 g, 25 mmol) was added. Under cooling in an ice bath (,58C), con-
4
centrated H SO (0.10 mL) was added, and the resulting mixture was stirred at
room temperature (15–188C) for 5 h. The mixture was filtered to remove
2
4
CuSO and neutralized with saturated NaHCO solution in an ice bath. The
4
3
addition of cold water (380 mL) caused precipitation of the crude product 5,
which was filtered by suction and washed with water, and dried over
MgSO (1.3 g, 37%). Crystallization from MeOH gave an analytical sample
4
as plates.
2
1
Mp 192–1948C; IR (KBr) n 2990, 1630, 1240 cm ; UV (MeOH) lmax
1
40 nm (log 1 4.89); H NMR (400 MHz, acetone-d ) d 1.13 (s, 6H, CH ),
2
6
3
1
.49 (s, 6H, CH ), 6.25 (d, 2H, J ¼ 5.1 Hz, C H þ C H), 6.54 (d, 2H,
3
1
10
J ¼ 5.1 Hz, C H þ C H), 7.01 (d, 2H, J ¼ 8.8 Hz, C H þ C H), 7.93 ppm
2
9
4
7
1
3
(
d, 2H, J ¼ 8.8 Hz, C H þ C H); C NMR (100.4 MHz, acetone-d ) d 28.1,
5
6
6
8
m/z (relative intensity) 356 (M , 19), 240 (93), 184 (100). Anal. Calcd. for
2.2, 108.8, 110.4, 113.1, 116.3, 126.8, 129.2, 134.2, 159.6 ppm; MS (EI)
þ
C H O : C, 67.41; H, 5.66. Found: C, 67.28; H, 5.69.
20 20 6
Tetraacetyl Derivatives 6 from Tetraol 2
(
[7]
Improved Procedure)
A mixture of tetraol 1 (5.0 g, 18 mmol), acetic anhydride (200 mL), and
pyridine (40 mL) was stirred at 508C for 5 h and then cooled to room tempera-
ture. The reaction mixture was extracted with diethyl ether (100 mL) with the
addition of a small amount of NaHCO saturated solution. The extract was
3
washed with dilute HCl and water and dried over MgSO . Evaporation of
4

4
322
Yamaye et al.
the solvent left a pale yellow solid 6 (4.9 g, 63%) that was analyzed by HPLC
ODS column). Recrystallization from diethyl ether gave 6a and 6b, and from
(
MeOH gave 6c. Spectroscopic data (IR, H NMR and C NMR, MS) and
1
13
[7]
elemental analysis of 6 were given in the literature.
1
a: H NMR (400 MHz, acetone-d ) d 2.04 (s, 6H, CH ), 2.06 (s, 6H,
6
6
6
6
3
CH ), 5.98 (s, 2H, C H þ C H), 6.62 (s, 2H, C H þ C H), 7.12 (d,
3
1
10
2
9
2
H, J ¼ 8.6 Hz, C H þ C H), 8.04 ppm (d, 2H, J ¼ 8.8 Hz,
4
7
C H þ C H).
5
6
1
b: H NMR (400 MHz, acetone-d ) d 2.04 (s, 6H, CH ), 2.08 (s, 6H,
6
3
CH ), 6.33 (s, 2H, C H þ C H), 6.58 (s, 2H, C H þ C H), 7.17 (d,
3
1
10
2
9
2
H, J ¼ 8.5 Hz, C H þ C H), 8.10 ppm (d, 2H, J ¼ 9.0 Hz,
4
7
C H þ C H).
5
6
1
c: H NMR (400 MHz, acetone-d ) d 2.15 (s, 6H, CH ), 2.38 (s, 6H,
6
3
CH ), 5.50 (s, 2H, C H þ C H), 6.17 (s, 2H, C H þ C H), 7.38 (d,
3
1
10
2
9
2
H, J ¼ 9.0 Hz, C H þ C H), 8.05 ppm (d, 2H, J ¼ 9.0 Hz,
4
7
C H þ C H).
5
6
REFERENCES
1
. Kito, T.; Yoshinaga, K.; Yamaye, M.; Mizobe, H. Base-Catalyzed Alky-
lation of 2-Naphthol with Glyoxal. J. Org. Chem. 1991, 56, 3336–3339.
. Fan, X.; Yamaye, M.; Kosugi, Y.; Okazaki, H.; Mizobe, H.; Yanai, T.;
Kito, T. Stereochemistry of the Products from the Alkylation of 2-Naphthol
with Glyoxal. J. Chem. Soc. Perkin Trans. 2 1994, 2001–2005.
. Fan, X.; Yanai, T.; Okazaki, H.; Yamaye, M.; Mizobe, H.; Kosugi, Y.;
Kito, T. Aromatic Compounds with 3a,6a-Dihydrofuro[2,3-b]Furan
Moiety. 2. Alkylation Products of Dihydroxynaphthalenes with 1,2-Dihy-
dronaphtho[2,3-b]Furan-1,2-Diol and Their Structure Analyses. J. Org.
Chem. 1995, 60, 5407–5413.
2
3
4
. Yamaye, M.; Ikeda, Y.; Cho (Toh), N.; Miura, Y.; Yoshinaga, T.;
Mukae, K.; Tsuru, T. Preparation and Optical Resolution of a New
Helical Lactone Carrying the 2,8-Dioxabicyclo[3.3.0]Octane Ring
System. Heterocycles 2004, 63, 137–143.
5
. Diol 1 and tetraol 2 have a similar relationship to sugars with respect to the
corresponding vicinal hydroxyl groups, accordingly related references are:
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Saccharides with Rare Earth Metal Ions: Synthesis and Characterization
of Pr(III)- and Nd(III)-Saccharide Complexes. Carbohydr. Res. 2000,

Isopropylidenation of Diol 1 and Tetraol 2
4323
328, 103–113. (b) Guo, J.; Zhang, X. Metal-Ion Interactions with Sugars.
The Crystal Structure and FTIR Study of an SrCl —Fructose Complex.
2
Carbohydr. Res. 2004, 339, 1421–1426; (c) Lu, Y.; Deng, G.; Miao, F.;
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3
3
plexes. Carbohydr. Res. 2004, 339, 1689–1696.
. Wang, Z.-X.; Wiebe, L.I.; Balzarini, J.; Clercq, E.D.; Knaus, E.E. Chiral
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6
5-fluoroaniline: “Cytosine Replacement” Analogues of deoxy-b-L-cytidine.
J. Org. Chem. 2000, 65, 9214–9219.
7
. Fan, X.; Yanai, T.; Yamaye, M.; Okazaki, H.; Kito, T. Base-Catalysed
Alkylation of 2,7-Naphthalenediol with Glyoxal. Isolation of Structurally
Intriguing Products and Their Stereochemistry. J. Chem. Res. (S) 1998,
4
08 [Chem. Res. (M) 1998 1538–1548].
Received in Japan May 24, 2004