A simple one-pot entry to cyclic ethers of varied ring sizes from diols via phosphonium ion induced iodination and base catalyzed Williamson etherification

Article abstract of DOI:10.1016/j.tetlet.2006.08.090

A novel and an efficient one-pot cyclization method using triphenylphosphine, iodine and a nitrogenous base has been established for the synthesis of cyclic ethers of various ring sizes. This appears to follow a two-step procedure, which includes preferen

Full text of DOI:10.1016/j.tetlet.2006.08.090

Tetrahedron Letters 47 (2006) 7783–7787
A simple one-pot entry to cyclic ethers of varied ring sizes
from diols via phosphonium ion induced iodination and
base catalyzed Williamson etherification
Biswajit Gopal Roy, Ashim Roy, Basudeb Achari and Sukhendu B. Mandal*
Department of Chemistry, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Kolkata 700 032, India
Received 23 June 2006; revised 14 August 2006; accepted 23 August 2006
Available online 15 September 2006
Abstract—A novel and an efficient one-pot cyclization method using triphenylphosphine, iodine and a nitrogenous base has
been established for the synthesis of cyclic ethers of various ring sizes. This appears to follow a two-step procedure, which includes
preferential substitution of one hydroxyl group by an iodide generated in situ followed by an intramolecular ring closure through the
attack of a free hydroxyl group or the more nucleophilic oxide ion.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Cyclic ethers are the common backbone of a large
number of natural products,1 nucleosides2 and antibiot-
ics,3 and their synthesis remains a compelling task for
synthetic organic chemists. A number of attempts
involving Lewis acid or transition metal catalyzed open-
ing of epoxy,4,5 cyclic sulfate6 or cyclic orthoester7 rings
by hydroxy groups, metal catalyzed cyclization of olefin-
alcohols,8 and Mitsunobu cyclization9 of diols have
been made in this regard, resulting in a number of new
methods for cycloetherification.10 The Mitsunobu cycli-
zation appears particularly attractive, but is restricted to
diols having at least one phenolic, benzylic, allylic or
anomeric hydroxy group. Most of the methods are also
multistep, low yielding or intolerant to acid labile
groups, and their applications are usually restricted to
the formation of five- and six-membered cyclic ethers.
However, the formation of cyclic ethers by cyclization
involving two unactivated hydroxyl groups is not well
known. During the work on a project directed towards
I
Ph3P
I
PPh3
+
I
I
(i)
ROH +
RO PPh3
+
HI
(ii)
Ph3P
HI
I
Im
+
(iii)
Im-H
SN2
I
+
RO PPh3
+
O=PPh3
RI +
I
(iv)
HO
I
1
I
I
H
I
HO
O
O
O
a
O
O
O
O
O
+
O
65%
O
H
O
O
O
HO
O
I
H
O
HO
O
1
2
HO
4
3
5
Scheme 1. Conversion of triol 1 to iodoolefin 2 and iodoether 3.
Reagents and conditions: (a) PPh3 (3.75 equiv), imidazole (3.75 equiv),
iodine (2.0 equiv), toluene, reflux.
SN2
I
H
O
O
O
O
H
I
O
O
Keywords: One-pot; Synthesis; Cyclic ethers; Diols; Iodination;
Etherification.
O
H
3
2
*
Corresponding author. Tel.: +91 332473 3491; fax: +91 332473
5197; e-mail: sbmandal@iicb.res.in
Figure 1. Probable mechanism of formation of 2 and 3 from 1.
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.08.090

7784
B. G. Roy et al. / Tetrahedron Letters 47 (2006) 7783–7787
Table 1. Cyclization of triol/diols to the cyclic ethers 6 and 14–20
the synthesis of carbohydrate derived molecules, we
treated 1 with triphenylphosphine-imidazole-iodine in
refluxing toluene to introduce an olefin moiety between
vicinal hydroxy groups.11 The reaction mixture yielded
(Scheme 1) two novel compounds,12 2, a hitherto
unknown C-3 a-iodo substitution product, and 3, a
five-membered fused oxacycle, in the ratio of 2:3. The
formation of products 2 and 3 suggested that the inter-
mediate diiodide 4 (formed in situ, Fig. 1) underwent
parallel reactions. Deiodination resulted in the forma-
tion of the expected olefin 5, which then underwent a
SN2 attack (after activation by PPh3) by an iodide ion
at C-3 to afford 2. On the other hand, an intramolecular
SN2 attack of the C-3 hydroxyl group in 4 on the termi-
nal iodide led to the five-membered iodo-substituted
cyclized product 3.
Entry Substrate Reagents/conditionsa Product
Yield
(%)
HO
H
HO
HO
H
1
2
O
45
O
O
O
a
O
O
O
H
HO
1
6
OH
H
O
O
O
O
60
a, b
O
O
O
HO
H
7
14
O
H
O
O
O
a, b
3
4
70
65
O
HO
OH
O
O
These results led us to speculate that the use of less
reagent to iodinate only the primary hydroxyl group
should furnish the cyclic ether after nucleophilic attack
by the second hydroxyl group. This was indeed realized,
allowing us to achieve a versatile, cost effective and rapid
one-pot synthesis of cyclic ethers directly from 1,n-diols.
H
O
8
15
HO
H
H
O
O
O
a, b
a, b
O
O
O
H
HO
9
16
Initially, when we carried out the reaction on 1 with
PPh3 (1.1 equiv), iodine (1 equiv) and imidazole
(2.5 equiv), only the five-membered cyclic ether 613 was
formed in 45% yield. In order to establish this reaction
as a potential method for the preparation of cyclic ethers
of different ring sizes from unactivated diols,14 we ap-
plied this method to substrates 7–13 to obtain products
14–2015 (Table 1). However, the reaction appeared to be
sluggish and required the addition of NaH for a quicker
cyclization.
HO
H
H
O
O
O
O
O
5
60
O
O
10
H
HO
17
HO
OH
H
H
O
O
O
O
O
6
7
8
a, b
23
62
72
O
O
O
O
H
11
18
Thus, the treatment of 716 with the reagent followed by
the addition of NaH (1 equiv) in the same reaction pot
at room temperature resulted in the formation of the
four-membered cyclic ether 14 (60%) in less than an
hour. During the formation of the six-membered cis-
fused cyclic ether 15 (70%), two newly generated spots
were detected by TLC after 45 min. The subsequent
addition of NaH (1 equiv) at room temperature con-
verted one of the spots to the other, that is, full conver-
sion to a six-membered cyclic ether was achieved in
5 min. Thus, addition of NaH appears to speed up the
reaction by facilitating SN2 attack by the more nucleo-
philic oxide ion. Similarly, the trans-fused bicyclic ethers
16 and 17 were prepared from their respective starting
materials 9 and 1017 in good yields. The dioxacyclohep-
tane derivative 18 was derived from the carbohydrate
precursor 11 using this method, though the yield was
unsatisfactory.18 Further, if the C-3 hydroxy group is
blocked by benzylation (1219), the reaction furnishes
the expected three-membered cyclic ether (19, 62%).
Therefore, the change in proportions of PPh3 and iodine
led to an epoxide formation instead of a double bond
generation as is typical for vicinal dihydroxy com-
pounds. The reaction was also successfully applied to
the formation of the spirocyclic product 2020 from 13.21
HO
HO
O
O
O
O
O
a, b
O
BnO
O
BnO
12
19
HO
HO
O
O
O
O
a, b
O
O
BnO
O
BnO
20
13
a (a) PPh3 (1.1 equiv), imidazole (2.5 equiv), iodine (1 equiv), toluene,
reflux, 120 min (for 1), 40–45 min (for 7–13); (b) NaH (1 equiv), rt,
5–10 min.
the reaction at higher temperatures to make it homo-
geneous. A better alternative involved the use of bases
such as Et3N and pyridine, which yielded homogeneous
mixtures at room temperature and led to an increase in
the yields (Table 2). To study the effect of solvent polar-
ity we carried out some of the reactions in DCM and
found no increase in the yield. It was noticed that iodin-
ation followed by a base-catalyzed cyclization at room
temperature using pyridine yielded the best results.
However, triol 1 was insoluble in toluene at room tem-
perature, and required refluxing for iodination, though
the cyclization proceeded without the addition of
NaH. The cyclization of the monoiodinated products,
As the use of imidazole as a base led to the generation of
a heterogeneous reaction mixture, we had to perform

B. G. Roy et al. / Tetrahedron Letters 47 (2006) 7783–7787
Table 2. Cyclization study using pyridine/triethyl amine
7785
b
Iodohydroxy
compounds
a
Cyclic ethers
1, n-Diols
Entry
Diol
Reagents/conditionsa
Product
Isolated yield (%) Py/Et3N
1
2
3
4
5
6
7
7
8
a, b
a, b
a, b
a, b
a, b
a, b
a, b
14
15
16
17
18
19
20
82/70
90/78
86/75
80/75
30/25
85/73
78/78
9
10
11
12
13
a (a) Ph3P (1.1 equiv), I2 (1 equiv), Py/Et3N (2.5 equiv), toluene, rt, 70–120 min; (b) NaH, rt, 5–10 min.
India). The authors gratefully acknowledge the Council
of Scientific and Industrial Research for providing
Senior Research Fellowships (to B.G.R. and A.R.)
and an Emeritus Scientist scheme (to B.A.).
HO
HO
H
I
O
O
a
O
O
68%
O
N
O
HN
H
22
21
References and notes
Scheme 2. Cyclization of amino alcohol 21 to amine 22. Reagents and
conditions: (a) PPh3 (3.75 equiv), imidazole (3.75 equiv), iodine
(2.0 equiv), toluene, reflux, 45 min.
1. (a) Garson, M. J. Chem. Rev. 1993, 93, 1699; (b)
Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897;
(c) Tinsley, J. M.; Roush, W. R. J. Am. Chem. Soc. 2005,
127, 10818; (d) Akiyama, M.; Isoda, Y.; Nishimoto, M.;
Kobayashi, A.; Togawa, D.; Hirao, N.; Kuboki, M.;
Ohira, S. Tetrahedron Lett. 2005, 46, 7483; (e) Trost, B.
M.; Machacek, M. R. J. Am. Chem. Soc. 2005, 127, 7014;
(f) Sanchez, C. C.; Keck, G. E. Org. Lett. 2005, 7, 3053.
2. (a) Danishefsky, S.; Hungate, R. J. Am. Chem. Soc. 1986,
108, 2486; (b) Hanessian, S.; Marcotte, S.; Machaalani,
R.; Huang, G. Org. Lett. 2003, 5, 4277.
3. Brimble, M. A. Pure Appl. Chem. 2000, 72, 1635.
4. (a) Nicolaou, K. C.; Shi, G.-Q.; Gunzner, J. L.; Gartner,
P.; Wallace, P. A.; Ouellette, M. A.; Shi, S.; Bunnage, M.
E.; Agrios, K. A.; Veale, C. A.; Hwang, C.-K.; Hutch-
inson, J.; Prasad, C. V. C.; Ogilvie, W. W.; Yang, Z.
Chem. Eur. J. 1999, 5, 628; (b) Evans, D. A.; Bender, S. L.;
Morris, J. J. Am. Chem. Soc. 1988, 110, 2506; (c) Hoye, T.
R.; Jenkins, S. A. J. Am. Chem. Soc. 1987, 109, 6196.
5. Wu, M. H.; Hansen, K. B.; Jacobsen, E. N. Angew. Chem.,
Int. Ed. 1999, 38, 2012.
derived easily from diols 8–12 with triphenylphosphine-
imidazole-iodine at room temperature, to afford the
corresponding ethers 15–19 necessitated the addition
of NaH. On the other hand, iodination of one of the
hydroxyl groups of 13 in toluene (being attached to
the quaternary carbon of the furanose moiety) was slow
and required a longer time (120 min) because of steric
hindrance. However, the cyclization occurred easily at
room temperature upon addition of sodium hydride.
We also decided to extend the methodology for the syn-
thesis of cyclic amines from amino alcohols. Indeed
21,22 the C-3 amino analogue of 1, underwent the reac-
tion smoothly, affording the cyclized product 22 in good
yield (Scheme 2). In this case addition of sodium hydride
was not required. The nucleophilic attack by nitrogen
at the terminal iodide appears to be faster than olefin
formation from the diiodide.
6. (a) Kalantar, T. H.; Sharpless, K. B. Acta Chem. Scand.
1993, 47, 307; (b) Byun, H.-S.; He, L.; Bittman, R.
Tetrahedron 2000, 56, 7051; (c) Beauchamp, T. J.; Powers,
J. P.; Rychnovsky, S. D. J. Am. Chem. Soc. 1995, 117,
12873.
In conclusion, a one-pot method has been developed for
the synthesis of cyclic ethers of varied ring sizes from
unactivated diols using easily available precursors and
cheap reagents. Considering the paucity of effective
methods for cyclic ethers, the present approach appears
to be the useful method for the synthesis of such mole-
cules. It is also shown to work with amino alcohols
to produce cyclic amines. Future work is aimed at the
generation of a variety of chiral heterocycles as well as
modified bicyclic nucleosides of biological importance.
7. Zheng, T.; Narayan, R. S.; Schomaker, J. M.; Borhan, B.
J. Am. Chem. Soc. 2005, 127, 6946.
8. (a) Blanc, A.; Toste, F. D. Angew. Chem., Int. Ed. 2006,
45, 2096; (b) Yang, C.-G.; Reich, N. W.; Shi, Z.; He, C.
Org. Lett. 2005, 7, 4553.
9. Wu, Q.; Simons, C. Synthesis 2004, 1533.
10. (a) Taber, D. F.; Pan, Y.; Zhao, X. J. Org. Chem. 2004, 69,
7234; (b) Boivin, T. L. B. Tetrahedron 1987, 43, 3309; (c)
Koert, U. Synthesis 1995, 115; (d) Fleming, P. R.;
Sharpless, K. B. J. Org. Chem. 1991, 56, 2869; (e)
Golding, B. T.; Hall, D. R.; Sakrikar, S. J. Chem. Soc.,
Perkin Trans. 1 1973, 1214.
11. (a) Garegg, P. J.; Samuelson, B. Synthesis 1979, 469; (b)
Shing, T. K. M.; Wong, C.-H.; Yip, T. Tetrahedron:
Asymmetry 1996, 7, 1323.
Acknowledgements
30
12. Data for 2: 1H NMR (CDCl3, 300 MHz): ½aꢀD +29.4 (c
The work has been supported by a grant from the
Department of Science and Technology (Govt. of
0.22, CHCl3); d 1.38 (s, 3H), 1.57 (s, 3H), 3.58 (dd, J = 4.3,

7786
B. G. Roy et al. / Tetrahedron Letters 47 (2006) 7783–7787
10.3 Hz, 1H), 4.50 (dd, J = 6.9, 10.0 Hz, 1H), 4.64 (t,
(CH), 103.8 (CH), 113.9 (C); ESIMS, m/z: 263 (M+Na)+.
J = 9.3 Hz, 1H), 5.36 (d, J = 10.3 Hz, 1H), 5.49 (d,
J = 17.1 Hz, 1H), 5.70–5.82 (m, 1H), 5.86 (d, J = 3.5 Hz,
1H); FABMS, m/z: 297 (M+H)+. Anal. Calcd for
C9H13IO3: C, 36.51; H, 4.43. Found: C, 36.32; H, 4.37.
Anal. Calcd for C13H20O4: C, 64.98; H, 8.39. Found: C,
30
64.82; H, 8.20. For 17: ½aꢀD +9.2 (c 0.49, CHCl3); 1H NMR
(CDCl3, 600 MHz): d 1.34 (s, 3H), 1.41–1.45 (m, 1H), 1.53
(s, 3H), 1.83–1.86 (m, 2H), 3.27–3.32 (m, 2H), 3.69 (dt,
J = 4.8, 10.2 Hz, 1H), 4.03–4.06 (m, 1H), 4.27 (t, J = 4.2,
9.6 Hz, 1H), 4.66 (t, J = 3.6 Hz, 1H), 5.83 (d, J = 3.6 Hz,
1H); 13C NMR (CDCl3, 150 MHz): d 25.8 (CH2), 26.0
(CH3), 26.2 (CH3), 48.2 (CH), 67.5 (CH2), 70.7 (CH2), 74.1
(CH), 79.9 (CH), 105.6 (CH), 112.2 (C); ESIMS, m/z: 223
(M+Na)+. Anal. Calcd for C10H16O4: C, 59.98; H, 8.05.
30
For 3: ½aꢀD +65.5 (c 1.15, CHCl3); 1H NMR (CDCl3,
300 MHz): d 1.33 (s, 3H), 1.50 (s, 3H), 4.18 (dd-like,
J = 3.7, 9.5 Hz, 1H), 4.31–4.35 (m, 2H), 4.63 (d,
J = 3.5 Hz, 1H), 4.88 (d, J = 3.0 Hz, 1H), 5.10 (d,
J = 3.0 Hz, 1H), 5.88 (d, J = 3.5 Hz, 1H); 13C NMR
(CDCl3, 75 MHz): d 24.7 (CH), 26.6 (CH3), 27.3 (CH3),
76.6 (CH2), 83.7 (CH), 85.0 (CH), 90.2 (CH), 107.0 (CH),
112.5 (C); FABMS, m/z: 313 (M+H)+. Anal. Calcd for
C9H13IO4: C, 34.63; H, 4.20. Found: C, 34.60; H, 4.13.
30
Found: C, 60.10; H, 7.95. For 18: ½aꢀD ꢁ32.6 (c 0.46,
CHCl3); 1H NMR (CDCl3, 300 MHz): d 1.32 (s, 3H), 1.49
(s, 3H), 3.56–3.69 (m, 3H), 3.87–3.98 (m, 2H), 4.15 (d,
J = 3.5 Hz, 1H), 4.23 (dd, J = 6.0, 12.4 Hz, 1H), 4.53–4.57
(m, 2H), 5.96 (d, J = 3.6 Hz, 1H); 13C NMR (CDCl3,
150 MHz): d 26.3 (CH3), 26.9 (CH3), 71.5 (CH2), 73.6
(CH2), 74.7 (CH2), 80.9 (CH), 85.2 (CH), 87.6 (CH), 105.3
(CH), 111.5 (C); ESIMS, m/z: 239 (M+Na)+. Anal. Calcd
for C10H16O5: C, 55.55; H, 7.46. Found: C, 55.38; H, 7.45.
´
´
13. Molas, M. P.; Matheu, M. I.; Castillon, S.; Isac-Garcıa, J.;
´
Hernandez-Mateo, F.; Calvo-Flores, F. G.; Santoyo-
´
Gonzalez, F. Tetrahedron 1999, 55, 14649.
14. The substrate 8 was prepared from 5-aldo-1,2-O-cyclo-
hexylidene-a-D-glucofuranose via Wittig reaction with
PPh3@CHCO2Et followed by LiAlH4 reduction.23 Simi-
larly, 9 was synthesized from the corresponding C-3
epimer.24 The substrate 11 was obtained from 3-O-methoxy-
carbonylmethyl-1,2:5,6-di-O-isopropylidene-a-D-gluco-
furanose25 through selective opening of the 5,6-acetonide
by HOAc, vicinal diol cleavage with NaIO4 and reduction
with NaBH4.
30
For 19: ½aꢀD ꢁ44.3 (c 0.96, CHCl3); 1H NMR (CDCl3,
300 MHz): d 1.31 (s, 3H), 1.46 (s, 3H), 2.78 (dd, J = 2.5,
5.0 Hz, 1H), 2.93 (dd, J = 3.8, 4.7 Hz, 1H), 3.29–3.33 (m,
1H), 3.75 (dd, J = 3.0, 7.0 Hz, 1H), 4.08 (d, J = 2.9 Hz,
1H), 4.64 (d, J = 3.2 Hz, 1H), 4.65 (partially merged d,
1H), 4.73 (d, J = 12.0 Hz, 1H), 5.95 (d, J = 3.5 Hz, 1H),
7.25–7.35 (m, 5H); 13C NMR (CDCl3, 75 MHz): d 26.6
(CH3), 27.2 (CH3), 47.3 (CH2), 48.6 (CH), 72.7 (CH2), 82.1
(CH), 82.5 (CH), 83.1 (CH), 105.8 (CH), 112.2 (C), 128.0
(2 · CH), 128.3 (CH), 128.9 (2 · CH), 137.8 (C); ESIMS,
m/z: 315 (M+Na)+. Anal. Calcd for C16H20O5: C, 65.74; H,
15. General procedure for the synthesis of the cyclic ethers 14–20
at room temperature: To a solution of a dihydroxy
compound (5 mmol) in dry toluene (25 mL) was added
triphenyl-phosphine (5.5 mmol) and pyridine (12.5 mmol),
and the mixture was stirred at rt for 5 min to afford a clear
solution. Iodine granules (5 mmol) were added portionwise
to the solution and stirring was continued at rt for 70–
120 min (as in Table 2). Oil-free NaH (10 mmol) was added
slowly and the mixture was stirred for 5–10 min at rt.
Excess NaH was destroyed by slow addition of cold water
to the reaction mixture. The solvent was washed with water
(10 mL), saturated Na2S2O3 solution (2 · 20 mL) and brine
(2 · 10 mL), dried over Na2SO4 (anhydrous), and evapo-
rated in vacuo to give a residue, which was purified by
column chromatography to yield the cyclic ethers. In the
case of 1, the above procedure was followed with imidazole
as base and with refluxing for 45 min to yield 6.13
30
6.90. Found: C, 65.58; H, 6.77. For 22: ½aꢀD +6.3 (c 0.55,
CHCl3); 1H NMR (CDCl3, 300 MHz): d 1.33 (s, 3H), 1.49
(s, 3H), 3.00 (dd, J = 5.4, 11.7 Hz, 1H), 3.17–3.37 (m, 2H),
3.53 (dd, J = 5.7, 13.6 Hz, 1H), 3.62 (d, J = 4.4 Hz, 1H),
3.79 (dd, J = 5.6, 11.3 Hz, 1H), 4.10 (d, J = 3.8 Hz, 1H),
4.52 (d, J = 2.2 Hz, 1H), 5.07–5.27 (m, 2H), 5.78–5.98 (m,
merged with a d, J = 3.2 Hz, at d 5.92, 2H); 13C NMR
(CDCl3, 75 MHz): d 22.5 (CH), 26.6 (CH3), 27.4 (CH3),
57.5 (CH2), 63.5 (CH2), 72.2 (CH), 83.5 (CH), 92.2
(CH), 107.0 (CH), 112.0 (C), 117.7 (CH2), 134.9 (CH);
ESIMS, m/z: 374 (M+Na)+. Anal. Calcd for C12H18INO3:
C, 41.04; H, 5.17; N, 3.99. Found: C, 40.86; H, 5.00; N,
3.80.
30
Characterization data for 14: ½aꢀD +31.2 (c 0.49, CHCl3);
1H NMR (CDCl3, 300 MHz): d 1.38 and 1.60 (br s, 10H),
4.25 (dd-like, J = 1.8, 7.6 Hz, 1H), 4.73–4.76 (m, 2H), 5.10
(d, J = 2.0 Hz, 1H), 5.21 (d, J = 3.7 Hz, 1H), 6.29 (d,
J = 3.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz): d 23.6
(CH2), 23.7 (CH2), 24.7 (CH2), 36.5 (CH2), 37.4 (CH2), 78.2
(CH), 78.3 (CH2), 84.1 (CH), 87.5 (CH), 107.7 (CH), 114.4
(C); ESIMS, m/z: 235 (M+Na)+. Anal. Calcd for
C11H16O4: C, 62.25; H, 7.60. Found: C, 62.20; H, 7.55.
16. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.;
Tatchell, A. R. Vogel’s Textbook of Practical Organic
Chemistry, 5th ed.; Addison Wesley Longman Limited:
Essex, England, 1997; p 657.
17. Prepared via oxidation of the C-3 OH of 1,2:5,6-di-O-
isopropylidene-a-D-glucofuranose, Wittig reaction with
Ph3P@CHCO2Et, selective removal of the 5,6-acetonide,
vicinal diol cleavage and stereocontrolled reduction26 of
the double bond along with the aldehyde group with
LiAlH4.
18. Reduction in the yield of 18 is due to the parallel
dehydroiodination of the intermediate iodide to form the
3-O-vinyl product (60%) [1H NMR (CDCl3, 300 MHz): d
1.33 (s, 3H), 1.52 (s, 3H), 3.82–3.96 (m, 3H), 4.18–4.20 (m,
1H), 4.38–4.42 (m, 2H), 4.60 (d, J = 3.6 Hz, 1H), 5.94 (d,
J = 3.3 Hz, 1H), 6.37 (dd, J = 7.0, 14.0 Hz, 1H)].
19. Roy, A.; Roy, B. G.; Achari, B.; Mandal, S. B. Tetra-
hedron Lett. 2004, 45, 5811.
30
For 15: ½aꢀD +23.6 (c 0.49, CHCl3); 1H NMR (CDCl3,
300 MHz): d 1.33–1.89 (m, 13H), 2.13 (br d, J = 14.0 Hz,
1H), 3.34 (t-like, J = 11.4 Hz, 1H), 3.85–3.88 (m, 2H), 4.18
(s, 1H), 4.42 (d, J = 3.5 Hz, 1H), 5.91 (d, J = 3.5 Hz, 1H);
13C NMR (CDCl3, 75 MHz): d 19.9 (CH2), 23.5 (CH2),
23.8 (CH2), 24.0 (CH2), 24.9 (CH2), 35.5 (CH2), 36.2 (CH2),
66.4 (CH2), 73.2 (CH), 78.8 (CH), 83.8 (CH), 104.7 (CH),
111.7 (C); ESIMS, m/z: 263 (M+Na)+. Anal. Calcd for
C13H20O4: C, 64.98; H, 8.39. Found: C, 64.80; H, 8.35.
30
For 16: ½aꢀD +9.8 (c 0.35, CHCl3); 1H NMR (CDCl3,
600 MHz): d 1.37 (m, 1H), 1.44 (m, 1H), 1.53–1.74 (m, 9H),
1.82 (t, J = 6.6 Hz, 2H), 2.27–2.30 (m, 1H), 2.95 (dd,
J = 3.6, 9.0 Hz, 1H), 3.46–3.51 (m, 1H), 3.74–3.78 (m, 1H),
4.10 (d-like, J = 9.0 Hz, 1H), 4.63 (t, J = 3.60 Hz, 1H), 5.78
(d, J = 3.60 Hz, 1H); 13C NMR (CDCl3, 150 MHz): d 23.5
(CH2), 23.8 (CH2), 24.1 (CH2), 24.9 (CH2), 28.8 (CH2), 35.5
(CH2), 35.6 (CH2), 69.4 (CH2), 72.7 (CH), 76.3 (CH), 82.2
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