A novel prins bicyclization strategy for the synthesis of sugar annulated furopyran scaffolds

Article abstract of DOI:10.1055/s-0033-1338708

A tandem Prins bicyclization of sugar-derived homoallylic diols with aldehydes has been accomplished using 10 mol% of In(OTf)₃ and 20 mol% of TsOH at ambient temperature to produce a novel series of sugar-annulated furopyran derivatives in good yields with high selectivity. This is the first report on Prins bicyclization of homoallylic diols derived from sugars. The cooperative catalysis between In(OTf)₃ and TsOH provides high conversions and enhanced reaction rates. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1338708

LETTER
▌1263
lAetteNr ovel Prins Bicyclization Strategy for the Synthesis of Sugar Annulated
Furopyran Scaffolds
Synthesis of Sugar Annulated Furopyran Scaffolds
Nikhil Srivastava, P. Puroshotham Reddy, Balasubramanian Sridhar, B. V. Subba Reddy*
Natural Product Chemistry, CSIR Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: basireddy@iict.res.in
Received: 14.02.2013; Accepted after revision: 12.04.2013
excellent yields (entries 8 and 9, Table 1). The substituent
Abstract: A tandem Prins bicyclization of sugar-derived homo-
on aromatic ring showed some effect on the conversion. It
allylic diols with aldehydes has been accomplished using 10 mol%
was observed that electron-rich aromatic aldehydes gave
the products in relatively lower yields than unsubstituted
of In(OTf)3 and 20 mol% of TsOH at ambient temperature to pro-
duce a novel series of sugar-annulated furopyran derivatives in
good yields with high selectivity. This is the first report on Prins bi- or halogenated aryl aldehydes (Table 1). The structure and
cyclization of homoallylic diols derived from sugars. The coopera-
tive catalysis between In(OTf)3 and TsOH provides high
conversions and enhanced reaction rates.
stereochemistry of 3c were confirmed by NOE and X-ray
experiments (see Supporting Information).8
Key words: Prins bicyclization, D-glucose, sugar-annulated
heterocycles, metal triflate, cooperative catalysis
O
O
O
H
HO
HO
O
O
1a
In(OTf)3, PTSA
The Prins cyclization is one of the most elegant methods
for the construction of tetrahydropyran derivatives with a
high degree of stereoselectivity1 and has been utilized for
the synthesis of several natural products.2 Typically, acid
catalysts are known to catalyze the Prins cyclization to
produce a large number of tetrahydropyran derivatives
under mild conditions.3,4 Recently, a cascade of Prins
cyclization has been reported to generate a wide range of
tetrahydropyran derivatives.5,6 However, to the best of our
knowledge, there are no reports on Prins bicyclization be-
tween an aldehyde and homoallylic diol derived from sug-
ars. These scaffolds are very useful for biological
screening against various cancer cell lines.
In continuation of our interest on Prins cyclization,7 we
herein report a novel method for the synthesis of sugar-
annulated furopyran derivatives through Prins bicycliza-
tion between sugar-based homoallylic diols and alde-
hydes. In a model reaction, we first attempted the cross-
coupling of sugar homoallylic diol 1a with benzaldehyde
(2) in the presence of 4 Å MS using 10 mol% In(OTf)3 and
20 mol% PTSA in dichloroethane. Interestingly, the reac-
tion proceeded smoothly at room temperature and the cor-
responding product 3a was obtained in 80% yield with cis
selectivity (entry 1, Table 1, and Scheme 1).
O
+
DCE, 0–25 °C
4 Å MS
O
H
O
O
H
H
2
3a
Scheme 1 Prins bicyclization of 1a with benzaldehyde (2)
The geometry of the olefin controls the stereoselectivity
of the reaction. It is known that cis-olefin gives the cis-
fused product exclusively. The use of molecular sieves is
essential to avoid the cleavage of sugar acetonide. The
combination of In(OTf)3 and TsOH (1:2) works more ef-
fectively than either In(OTf)3 or TsOH alone. The high
catalytic activity of the above reagent system may be ex-
plained through a cooperative catalysis between In(OTf)3
and TsOH.9 Other Brønsted acids such as TFA, TfOH,
CSA as well as Lewis acids such as Sc(OTf)3, Yb(OTf)3,
In(OTf)3 were screened for this conversion. Among them,
the combination of In(OTf)3 and TsOH (1:3) afforded the
best results in Prins bicyclization (Table 1). However, in
the absence of catalyst, no reaction was observed under
similar conditions. Next, we examined the effect of vari-
ous solvents such as tetrahydrofuran, 1,2-dimethoxy-
ethane and 1,2-dichloroethane. Among them, 1,2-
dichloroethane gave the best results. Mechanistically, the
reaction is expected to proceed through oxocarbenium ion
which is formed in situ from hemiacetal, likely after acti-
vation of the aldehyde with PTSA. Subsequent attack of
the olefin on oxocarbenium generates the carbocation
which is simultaneously trapped with a tethered second-
ary hydroxyl group leading to the formation of sugar-
annulated furopyran as depicted in Scheme 2.
Inspired by the above result, we extended this method to
various aldehydes such as m-tolualdehyde, m-methoxy-
benzaldehyde, p-methoxybenzaldehyde, p-fluorobenz-
aldehyde, p-chlorobenzaldehyde and p-bromobenz-
aldehyde. Interestingly, several aromatic aldehydes par-
ticipated effectively in this reaction (entries 1–9, Table 1).
Remarkably, a sterically hindered 2-naphthaldehyde and
1-pyrenecarboxaldehyde also gave the desired products in
SYNLETT 2013, 24, 1263–1268
Advanced online publication: 08.05.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1338708; Art ID: ST-2013-D0146-L
© Georg Thieme Verlag Stuttgart · New York

1264
N. Srivastava et al.
LETTER
Table 1 Prins Bicyclization of Sugar-Derived Homoallylic Diols with Aldehydes
Entry Homoallylic diol
Aldehyde 2
Product 3a
Time (h) Yield (%)b
O
CHO
O
O
H
H
H
O
O
O
1
1a
2a
3a
6.0
80
O
HO
O
O
O
O
H
OH
O
Me
O
Me
CHO
2
1a
2b
3b
6.1
68
O
H
O
OMe
O
MeO
CHO
3
1a
2c
3c
5.8
78
O
H
O
OMe
CHO
O
H
H
H
4
5
6
1a
1a
1a
2d
2e
2f
3d
3e
3f
6.2
5.5
6.0
75
80
82
O
MeO
O
O
O
O
O
O
H
O
F
CHO
O
O
F
H
O
Cl
CHO
O
O
Cl
H
O
Synlett 2013, 24, 1263–1268
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Sugar Annulated Furopyran Scaffolds
1265
Table 1 Prins Bicyclization of Sugar-Derived Homoallylic Diols with Aldehydes (continued)
Entry Homoallylic diol
Aldehyde 2
Product 3a
Time (h) Yield (%)b
Br
O
CHO
O
H
7
1a
2g
3g
5.0
85
Br
O
O
H
O
CHO
O
H
8
1a
2h
3h
5.2
82
O
O
O
H
O
CHO
9
1a
2i
3i
5.0
87
O
H
O
O
O
H
O
F
O
F
O
O
H
CHO
10
1b
2j
3j
6.0
79
O
O
HO
O
O
OH
H
O
a All products were characterized by NMR, IR and mass spectroscopy.
b Yield refers to pure products after chromatography.
In order to demonstrate the scope of this method, the reac- In summary, we have demonstrated a novel approach for
tion was also performed with acetonide-protected sugar the synthesis of sugar-annulated furopyran derivatives
homoallylic diol 1b. The cross-coupling of 1b with 2- through Prins bicyclization using a combination of
fluorobenzaldehyde proceeded well under similar condi- In(OTf)3 and PTSA. This method provides a direct access
tions to afford the desired product 3j in 78% yield with to the synthesis of a wide range of sugar-fused furopyrans
cis selectivity (entry 10, Table 1).
in a single-step process. This approach is highly stereose-
lective, affording the cis-fused tricyclic ethers in a single-
step process.
The present method is simple and convenient and also
provides the desired products in good to excellent yields
with high stereoselectivity. All the products were charac-
terized and confirmed by NMR, IR and mass spectrome-
try. The scope and generality of this process is illustrated
with respect to various aldehydes and the results are pre-
sented in Table 1.10
Acknowledgment
N.S. thanks CSIR, New Delhi for the award of a fellowship.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnuIpofoiprmntgirStanoIuifpog
r
t
iornat
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1263–1268

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N. Srivastava et al.
LETTER
(c) Tamiya, J.; Sorensen, E. J. Tetrahedron 2003, 59, 6921.
(d) Cho, Y. S.; Kim, H. Y.; Cha, J. H.; Pae, A. N.; Koh, H.
Y.; Choi, J. H.; Chang, M. H. Org. Lett. 2002, 4, 2025.
(e) Fenster, E.; Fehl, C.; Aube, J. Org. Lett. 2011, 13, 2614.
(7) (a) Yadav, J. S.; Prashant, B.; Chakravarthy, P. P.; Reddy, B.
V. S.; Sarma, A. V. S.; Basha, S. J.; Sridhar, B.; Grée, R. J.
Org. Chem. 2010, 75, 2081. (b) Reddy, B. V. S.; Prashant,
B.; Yadav, J. S.; Sridhar, B.; Grée, R. J. Org. Chem. 2011,
76, 7677; and references cited therein.
O
O
O
O
O
δ
O
In(OTf)3
δ
O
OH
– OH
+
..
OH
R
H
OH
..
O
R
(8) CCDC 901996 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
(9) Prashant, B.; van de Weghe, P.; Reddy, B. V. S.; Yadav, J.
S.; Gree, R. Chem. Commun. 2012, 48, 9316.
O
O
O
– H
O
(10) General Procedure: To a stirred solution of homoallylic
diol (1a; 100 mg, 0.37 mmol) in the presence of 4 Å MS
were added aldehyde (2, 0.44 mmol), followed by In(OTf)3
(10 mol%) and TsOH (20 mol%) in anhyd DCE (5 mL) at 0
°C. The resulting mixture was stirred at r.t. under a nitrogen
atmosphere for the specified time (Table ). After completion
of the reaction as indicated by TLC, the mixture was
quenched with sat. aq NaHCO3 solution (0.5 mL) and
extracted with CH2Cl2 (2 × 10 mL). The combined organic
phases were washed with brine (3 × 2 mL), dried over anhyd
Na2SO4 and concentrated in vacuo. The crude product was
purified by silica gel column chromatography (60–120
mesh) using EtOAc–hexane (3:7) as eluent to afford the pure
product 3.
R
O
cis-fused
Scheme 2 A plausible reaction pathway
References and Notes
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(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-Phenyloctahydro-
3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]furo[2′,3′:4,5]furo-
25
[3,2-c]pyran-2,1′-cyclohexane) (3a): viscous liquid; [α]D
+16.9 (c 0.5, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 1.47–
1.65 (m, 10 H), 1.85–1.94 (m, 2 H), 2.39–2.46 (m, 1 H),
3.45–3.53 (m, 1 H), 4.16–4.21 (m, 1 H), 4.35 (d, J = 3.1 Hz,
1 H), 4.39 (t, J = 3.1 Hz, 1 H), 4.45 (dd, J = 7.9, 9.5 Hz, 1 H),
4.55 (d, J = 3.1 Hz, 1 H), 4.71 (d, J = 4.7 Hz, 1 H), 6.03 (d,
J = 3.9 Hz, 2 H), 7.25–7.31 (m, 1 H), 7.36 (t, J = 7.1 Hz, 2
H), 7.51 (d, J = 7.9 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ
= 23.5, 23.7, 24.8, 31.9, 31.4, 36.6, 36.1, 47.6, 65.5, 77.2,
78.3, 82.8, 83.5, 87.6, 107.0, 126.3, 127.5, 128.3. IR (neat):
3430, 2927, 2854, 1731, 1074, 804, 701 cm–1. ESI–MS: m/z
= 359. HRMS (ESI): m/z [M + Na]+ calcd for C21H26O5:
381.1672; found: 381.1676.
(2) (a) Crane, E. A.; Scheidt, K. A. Angew. Chem. Int. Ed. 2010,
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Eur. J. Org. Chem. 2007, 792. (e) Epstein, O. L.; Rovis, T.
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Willis, C. L. Org. Lett. 2002, 4, 3407. (b) Dobbs, A. P.;
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(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-(m-Tolyl)octahydro-
3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]furo [2′,3′:4,5]furo-
[3,2-c]pyran-2,1′-cyclohexane) (3b): viscous liquid; [α]D
25
+35.5 (c 0.25, CHCl3). 1H NMR (300 MHz, CDCl3): δ =
1.40–1.70 (m, 10 H), 1.84–1.95 (m, 2 H), 2.34–2.38 (s, 3 H),
2.39–2.46 (m, 1 H), 3.43–3.46 (m, 1 H), 4.15–4.23 (m, 1 H),
4.36 (d, J = 3.0 Hz, 1 H), 4.41–4.49 (m, 2 H), 4.57 (d, J = 3.7
Hz, 1 H), 4.68 (d, J = 4.5 Hz, 1 H), 6.05 (d, J = 3.7 Hz, 1 H),
7.10 (d, J = 6.7 Hz, 1 H), 7.25–7.43 (m, 3 H). 13C NMR (75
MHz, CDCl3): δ = 21.4, 23.6, 23.8, 24.8, 31.5, 31.9, 36.3,
36.6, 47.6, 65.6, 77.2, 78.4, 82.8, 83.5, 87.5, 107.0, 123.4,
127.1, 128.1, 128.2. IR (neat): 3434, 2929, 2854, 1734,
1454, 1109, 772 cm–1. ESI–MS: m/z = 373 [M + H]+. HRMS
(ESI): m/z [M + Na]+ calcd for C22H28O5: 395.1829; found:
395.1831.
(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-Phenyloctahydro-
3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]furo[2′,3′:4,5]furo-
25
[3,2-c]pyran-2,1′-cyclohexane) (3c): viscous liquid; [α]D
+22 (c 0.3, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 1.30–
1.61 (m, 10 H), 1.88–1.91 (m, 2 H), 2.40 (m, 1 H), 3.46–3.52
(m, 1 H), 3.84 (s, 3 H), 4.15–4.21 (m, 1 H), 4.35 (d, J = 3.0
Hz, 1 H), 4.40–4.46 (m, 2 H), 4.58 (d, J = 4.0 Hz, 1 H), 4.68
(d, J = 4.0 Hz, 1 H), 6.04 (d, J = 4.0 Hz, 1 H), 6.85 (dd, J =
Synlett 2013, 24, 1263–1268
© Georg Thieme Verlag Stuttgart · New York

LETTER
3.0, 9.0 Hz, 1 H), 7.00 (d, J = 8.0 Hz, 1 H), 7.23–7.28 (m, 2
Synthesis of Sugar Annulated Furopyran Scaffolds
1267
NH4]+. HRMS (ESI): m/z [M + Na]+ calcd for C21H25BrO5:
459.0777; found: 459.0777.+
H). 13C NMR (75 MHz, CDCl3): δ = 23.6, 23.8, 24.8, 36.2,
36.7, 47.5, 55.3, 65.6, 77.2, 78.5, 82.9, 83.5, 87.4, 106.9,
111.2, 112.2, 114.5, 118.8, 129.1, 141.6. IR (neat): 3455,
2930, 2855, 1729, 1603, 1107, 772 cm–1. ESI–MS: m/z = 389
[M + H]+. HRMS (ESI): m/z [M + Na]+ calcd for C22H28O6:
411.1778; found: 411.1767.
(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-(Naphthalen-2-
yl)octahydro-3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]-
furo[2′,3′:4,5]furo[3,2-c]pyran-2,1′-cyclohexane) (3h):
viscous liquid; [α]D25 +9 (c 0.25, CHCl3). 1H NMR (500
MHz, CDCl3): δ = 1.40–1.67 (m, 10 H), 1.87–1.99 (m, 2 H),
2.52–2.58 (m, 1 H), 3.53–3.60 (m, 1 H), 4.22–4.29 (m, 1 H),
4.37 (d, J = 3.0 Hz, 1 H), 4.40 (t, J = 3.0 Hz, 1 H), 4.50 (q, J
= 9.0 Hz, 1 H), 4.58 (d, J = 4.0 Hz, 1 H), 4.90 (d, J = 4.0 Hz,
1 H), 6.02 (d, J = 3.0 Hz, 1 H), 7.46–7.51 (m, 2 H), 7.68 (d,
J = 7.0 Hz, 1 H), 7.82–7.91 (m, 3 H), 7.97 (s, 1 H). 13C NMR
(75 MHz, CDCl3): δ = 23.5, 23.7, 24.8, 31.5, 36.1, 36.5,
47.6, 65.6, 77.2, 78.3, 82.8, 83.5, 87.6, 107.0, 113.7, 124.3,
125.1, 125.7, 125.9, 127.6, 128.1, 127.6. IR (neat): 2924,
2852, 1736, 1461, 1219, 772 cm–1. ESI–MS: m/z = 409 [M +
H]+. HRMS (ESI): m/z [M + Na]+ calcd for C25H28O5:
431.1829; found: 431.1822.
(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-(4-Methoxy-
phenyl)octahydro-3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]-
furo[2′,3′:4,5]furo[3,2-c]pyran-2,1′-cyclohexane) (3d):
viscous liquid; [α]D25 +11 (c 0.25, CHCl3). 1H NMR (500
MHz, CDCl3): δ = 1.45–1.65 (m, 10 H), 1.82–1.91 (m, 2 H),
2.35–2.41 (m, 1 H), 3.42–3.52 (m, 1 H), 3.81 (s, 3 H), 4.13–
4.20 (m, 1 H), 4.35 (d, J = 2.9 Hz, 1 H), 4.39–4.44 (m, 2 H),
4.57 (d, J = 3.9 Hz, 1 H), 4.66 (d, J = 3.9 Hz, 1 H), 6.04 (d,
J = 3.9 Hz, 1 H), 6.90 (d, J = 7.7 Hz, 2 H), 7.45 (d, J = 8.7
Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 23.6, 23.8, 24.8,
31.9, 36.2, 47.9, 55.2, 65.6, 78.1, 82.9, 83.6, 87.6, 107.0,
112.2, 113.6, 127.7. IR (neat): 2924, 2853, 1735, 1458,
1106, 1070 cm–1. ESI–MS: m/z = 406 [M + NH4]+. HRMS
(ESI): m/z [M + Na]+ calcd for C22H28O6: 411.1778; found:
411.1767.
(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-(4,5a1-Dihydro-
pyren1yl)octahydro-3aH-spiro([1,3]dioxolo-
[4′′,5′′:4′,5′]furo[2′,3′:4,5]furo[3,2-c]pyran-2,1′-
cyclohexane) (3i): semi-solid; [α]D25 +194 (c 0.25, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 1.30–1.61 (m, 10 H), 1.98–
2.09 (m, 2 H), 2.76–2.86 (m, 1 H), 3.60–3.80 (m, 1 H), 4.03
(t, J = 3.0 Hz, 1 H), 4.26 (d, J = 3.0 Hz, 1 H), 4.31–4.40 (m,
1 H), 4.56 (d, J = 3.7 Hz, 1 H), 4.80 (dd, J = 8.3, 9.0 Hz, 1
H), 5.82 (d, J = 4.5 Hz, 1 H), 6.04 (d, J = 3.7 Hz, 2 H), 7.95–
8.04 (m, 1 H), 8.07 (d, J = 3.7 Hz, 1 H), 8.11 (d, J = 1.5 Hz,
2 H), 8.18 (dd, J = 3.0, 4.5 Hz, 2 H), 8.29 (d, J = 8.3 Hz, 1
H), 8.60 (d, J = 7.5 Hz, 1 H). 13C NMR (75 MHz, CDCl3): δ
= 23.5, 23.6, 24.7, 36.0, 36.6, 46.9, 65.9, 74.6, 76.9, 82.9,
83.4, 87.5, 106.9, 112.2, 121.6, 124.4, 124.9, 125.2, 125.3,
125.4, 125.7, 126.1, 126.9, 127.6, 127.7, 130.3, 130.4,
131.2, 133.6. IR (neat): 3445, 2929, 2854, 1729, 1366, 1106,
846 cm–1. ESI–MS: m/z = 505 [M + Na]+. HRMS (ESI): m/z
[M + Na]+ calcd for C31H30O5: 505.1985; found: 505.1982.
(3aR,4aR,5R,9aS,9bR)-5-(2-Fluorophenyl)-2,2-
(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-(4-Fluoro-
phenyl)octahydro-3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]-
furo[2′,3′:4,5]furo[3,2-c]pyran-2,1′-cyclohexane) (3e):
semi-solid; [α]D25 +17 (c 0.5, CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 1.45–1.65 (m, 10 H), 1.82–1.93 (m, 2 H), 2.36–
2.42 (m, 1 H), 3.44–3.51 (m, 1 H), 4.14–4.20 (m, 1 H), 4.34–
4.37 (s, 2 H), 4.43 (dd, J = 7.7, 11.0 Hz, 1 H), 4.57 (d, J = 3.3
Hz, 1 H), 4.69 (d, J = 4.4 Hz, 1 H), 6.02 (d, J = 3.3 Hz, 1 H),
7.05 (t, J = 8.8 Hz, 2 H), 7.50 (dd, J = 3.3, 5.5 Hz, 2 H). 13
NMR (75 MHz, CDCl3): δ = 23.6, 23.8, 24.8, 31.4, 36.1,
C
36.6, 47.7, 65.5, 77.7, 82.7, 83.6, 87.5, 107.0, 112.3, 115.0,
115.1, 128.0, 128.1, 135.9. IR (neat): 3460, 2928, 2854,
1728, 1602, 1102, 800 cm–1. ESI–MS: m/z = 377 [M + H]+.
HRMS (ESI): m/z [M + Na]+ calcd for C21H25FO5: 399.1578;
found: 399.1574.
(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-(4Chlorophenyl)-
octahydro-3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]-
dimethyloctahydro-3aH-([1,3]dioxolo[4′′,5′′:4′,5′]furo-
[2′,3′:4,5]furo[3,2-c]pyran) (3j): [α]D25 +50.2 (c 0.50,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 1.30–1.75 (m, 6
H), 1.80–1.98 (m, 2 H), 2.27–2.38 (m, 2 H), 3.47–3.58 (m, 1
H), 4.13–4.25 (m, 1 H), 4.35 (d, J = 10.8 Hz, 1 H), 4.42–4.50
(m, 1 H), 4.58 (d, J = 2.8 Hz, 1 H), 5.07 (d, J = 2.7 Hz, 1 H),
6.02 (d, J = 3.0 Hz, 1 H), 6.93–7.09 (m, 2 H), 7.18–7.41 (m,
1 H), 7.76–7.86 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ =
22.7, 26.6, 26.9, 45.7, 62.1, 65.5, 71.4, 83.2, 83.9, 87.4,
107.4, 111.5, 114.3, 114.5, 123.9, 124.4, 124.5, 127.2,
127.3, 128.7, 128.8, 157.9, 159.8. IR (neat): 2925, 2854,
1742, 1492, 1459, 1374, 1222, 1111, 1075, 771 cm–1. ESI–
MS: m/z = 359 [M + Na]+.
[(Z)-4-Hydroxybut-1-en-1-yl]tetrahydrospiro(cyclo-
hexane-1,2′-furo[2,3-d][1,3]dioxol)-6′-ol (1a): [α]D25 –22.5
(c 0.5, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 1.35–1.74
(m, 10 H), 2.32–2.52 (m, 2 H), 3.66–3.80 (m, 2 H), 4.20 (d,
J = 2.2 Hz, 1 H), 4.57 (d, J = 3.7 Hz, 1 H), 4.95 (dd, J = 2.2,
3.0 Hz, 1 H), 5.60–5.77 (m, 2 H), 5.97 (d, J = 3.7 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 23.5, 23.9, 24.8, 31.7, 35.8,
36.4, 61.3, 77.2, 78.0, 84.7, 103.9, 112.1, 126.5, 131.2. IR
(neat): 3421, 2934, 2858, 1655, 1111, 1069, 1013, 953, 802
cm–1. ESI–MS: m/z = 293 [M + Na]+. HRMS: m/z [M + Na]+
calcd for C14H22O5: 293.1359; found: 293.1353.
furo[2′,3′:4,5]furo[3,2-c]pyran-2,1′-cyclohexane) (3f):
semi-solid; [α]D25 +19 (c 0.5, CHCl3). 1H NMR (500 MHz,
CDCl3): δ = 1.46–1.60 (m, 10 H), 1.86–1.94 (m, 2 H), 2.37–
2.45 (m, 1 H), 3.43–3.53 (m, 1 H), 4.13–4.21 (m, 1 H), 4.34–
4.38 (m, 2 H), 4.45 (dd, J = 7.5, 10.5 Hz, 1 H), 4.58 (d, J =
3.7 Hz, 1 H), 4.70 (d, J = 4.5 Hz, 1 H), 6.03 (d, J = 3.7 Hz, 1
H), 7.32–7.38 (m, 2 H), 7.42–7.48 (m, 2 H). 13C NMR (75
MHz, CDCl3): δ = 23.6, 23.8, 24.9, 31.4, 36.1, 36.6, 47.5,
65.5, 77.5, 82.7, 83.6, 87.6, 107.0, 112.3, 127.8, 128.4,
138.7. IR (neat): 3782, 3682, 2930, 2855, 1732, 1105, 823
cm–1. ESI–MS: m/z = 393 [M + H]+. HRMS (ESI): m/z [M +
Na]+ calcd for C21H25ClO5: 415.1282; found: 415.1275.
(3aR,4aR,4bS,5R,8aS,9aS,9bR)-5-(4-Bromophenyl)-
octahydro-3aH-spiro([1,3]dioxolo[4′′,5′′:4′,5′]-
furo[2′,3′:4,5]furo[3,2-c]pyran-2,1′-cyclohexane) (3g):
solid; mp 146–148 °C; [α]D25 +23.8 (c 0.25, CHCl3). 1H
NMR (500 MHz, CDCl3): δ = 1.42–1.66 (m, 10 H), 1.82–
1.92 (m, 2 H), 2.35–2.45 (m, 1 H), 3.42–3.54 (m, 1 H), 4.12–
4.21 (m, 1 H), 4.33–4.38 (m, 2 H), 4.45 (dd, J = 7.5, 10.5 Hz,
1 H), 4.57 (d, J = 3.8 Hz, 1 H), 4.68 (d, J = 4.5 Hz, 1 H), 6.02
(d, J = 3.8 Hz, 1 H), 7.39 (d, J = 8.3 Hz, 2 H), 7.50 (d, J = 9.0
Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 23.5, 23.7, 24.8,
31.3, 36.0, 36.6, 47.3, 65.4, 76.8, 77.5, 82.7, 83.5, 87.6,
106.9, 112.3, 121.3, 128.0, 131.3, 139.1. IR (neat): 3451,
2933, 2856, 1631, 1108 cm–1. ESI–MS: m/z = 454 [M +
{(E)-[5-(4-Hydroxy-but-1-enyl)-2,2-dimethyl]tetra-
hydrofuro[2,3-d][1,3]dioxol}-6-ol (1b): [α]D25 –42.2 (c
0.61, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 1.20–1.33
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1263–1268

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N. Srivastava et al.
LETTER
(m, 6 H), 2.42–2.51 (m, 1 H), 3.61–3.79 (m, 2 H), 4.12 (d, J
= 2.6 Hz, 1 H), 4.51 (d, J = 3.7 Hz, 1 H), 4.84–4.91 (m, 1 H),
5.55–5.72 (m, 2 H), 5.89 (d, J = 3.5 Hz, 1 H). 13C NMR (75
MHz, CDCl3): δ = 26.1, 26.7, 31.6, 61.2, 76.3, 77.9, 85.2,
104.3, 111.4, 126.4, 131.2. IR (neat): 3363, 2978, 2927,
1376, 1248, 1217, 1163, 1071, 1008, 946 cm–1. ESI–MS: m/z
= 230 [M + Na]+. HRMS: m/z calcd for C11H18O5: 253.1044
[M + Na]+; found: 253.1046.
Synlett 2013, 24, 1263–1268
© Georg Thieme Verlag Stuttgart · New York