First example of the activation of polymethylhydrosiloxane with molecular iodine: A facile synthesis of 3,6-dihydropyran derivatives

Article abstract of DOI:10.1016/j.tetlet.2005.02.068

Glycals react rapidly with polymethylhydrosiloxane (PMHS) in the presence of a catalytic amount of molecular iodine under mild conditions to afford the corresponding 3,6-dihydropyran derivatives in excellent yields. Et ₃SiH/I₂ was al

Full text of DOI:10.1016/j.tetlet.2005.02.068

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 2687–2690
First example of the activation of polymethylhydrosiloxane with
molecular iodine: a facile synthesis of 3,6-dihydropyran derivatives
J. S. Yadav,* B. V. Subba Reddy, K. Premalatha and T. Swamy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 14 July 2004; revised 31 January 2005; accepted 10 February 2005
Abstract—Glycals react rapidly with polymethylhydrosiloxane (PMHS) in the presence of a catalytic amount of molecular iodine
under mild conditions to afford the corresponding 3,6-dihydropyran derivatives in excellent yields. Et3SiH/I2 was also found to be
effective for this conversion.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Naturally occurring carbohydrates have been exten-
sively used as chiral pool starting materials in the syn-
thesis of biologically active natural products.1 The
ready availability of a wide range of carbohydrates in
nature, each having several chiral centres, coupled with
their well-defined stereochemistry, make them useful
intermediates in organic synthesis.1a,2 Glycals are known
to undergo acid-catalyzed allylic rearrangement with
various nucleophiles to afford pseudoglycals or 2,3-
unsaturated glycosides.3,4 Pseudoglycals are versatile
chiral building blocks for the synthesis of glycoconju-
gates and polyether antibiotics.5 Typically, boron trifluo-
ride, titanium tetrachloride and indium trichloride are
employed as catalysts in the allylic transposition of gly-
cals with triethylsilane.6 However, many of these re-
agents are corrosive, moisture sensitive and are
required in stoichiometric amounts. Therefore, the
development of simple and inexpensive reagents, which
are more efficient and provide convenient procedures
with improved yields, are necessary. Owing to its unique
catalytic properties, iodine has been extensively used for
a plethora of organic transformations including glycosi-
dation reactions.7
and soluble hydrogen source, for the reduction of glucal
acetates via Ferrier rearrangement. Initially, we at-
tempted the allylic transposition of 3,4,6-tri-O-acetyl-
D-glucal 1 with PMHS 2 using 2.5 mol % of molecular
iodine as the catalyst. The reaction went to completion
within 3.0 h and the product 3a was obtained in 92%
yield (Scheme 1).11
Encouraged by this result we turned our attention to
various other glycals. D-Glucal derivatives 3,4,6-tri-O-
methyl, 3,4,6-tri-O-allyl and 3,4,6-tri-O-benzyl-D-glucals
were all converted into their corresponding 3,6-dihydro-
2H-2-pyrans using this procedure (Table 1 entries b–d).
Other glycals such as 3,4,6-tri-O-acetyl-D-galactal, 3,4-
di-O-acetyl-L-rhamnal, 3,4-di-O-acetyl-D-xylal and 3,4-
di-O-acetyl-D-arabinal also afforded the respective
dihydropyran derivatives in high yields under similar
conditions (Table 1 entries e–h). Hexa-O-acetyl-D-lactal,
derived from the disaccharide, a-D-lactose, gave the cor-
responding 3,6-dihydro-2H-2-pyran derivative in 87%
yield (Table 1, entry i, Scheme 2).
Similarly, hexa-O-acetyl-D-maltal derived from the
disaccharide, a-D-maltose, also reacted smoothly with
PMHS to afford the corresponding pyran derivative in
In continuation of our interest in the catalytic applica-
tions of molecular iodine for various organic transform-
ations,8–10 we describe herein the use of molecular
iodine as the catalyst for the activation of poly-
methylhydrosiloxane (PMHS), which is an inexpensive
O
I2
AcO
AcO
O
PMHS
+
AcO
AcO
CH2Cl2 , r.t.
OAc
1a
Keywords: Glycals; Molecular iodine; PMHS; Dihydropyrans.
*
2
3a
Corresponding author. Fax: +91 40 27160387; e-mail: yadav@
iict.res.in
Scheme 1.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.02.068

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J. S. Yadav et al. / Tetrahedron Letters 46 (2005) 2687–2690
Table 1. PMHS/I2-promoted synthesis of 3,6-dihydropyrans from glycals
Entry
a
Glycals 1
Dihydropyrans 3a
Time (h)
3.0
Yield (%)b
92 (71)c
O
O
AcO
AcO
AcO
AcO
OAc
O
O
MeO
MeO
MeO
b
c
d
e
f
3.5
3.0
4.0
3.5
3.0
2.5
3.0
86
MeO
OMe
O
O
O
O
O
82
O
O
O
BnO
BnO
O
BnO
90
BnO
OBn
O
AcO
AcO
O
AcO
87 (96)c
85 (72)c
86 (79)c
82
AcO
OAc
O
Me
O
O
Me
AcO
AcO
OAc
O
g
h
AcO
AcO
OAc
O
O
O
AcO
AcO
AcO
OAc
O
AcO
O
O
O
O
i
j
AcO
AcO
AcO
AcO
4.0
5.0
87
85
OAc
OAc
OAc
OAc
OAc
O
O
AcO
O
AcO
O
O
O
AcO
AcO
AcO
AcO
OAc
OAc
OAc
OAc
OAc
a All products were characterized by IR, 1H, 13C NMR and mass spectroscopy.
b Isolated and unoptimized yields.
c Yields reported in parentheses are literature yields for known compounds prepared via silane/InCl3 reduction.6b
85% yield (Table 1 entry j). All products were character-
ized by 1H, 13C NMR and IR spectroscopy and also by
comparison with authentic compounds.4,6,11 There are
several advantages in the use of iodine as the catalyst
for this transformation, which include high yields of
products, cleaner reaction profiles and easy availability
of the catalyst at low cost. In addition, the reaction con-
ditions are amenable for scaling up the reaction. Among
the various catalysts such as scandium triflate, ytterbium
triflate, cerium triflate, indium triflate and indium chlo-
ride employed for this conversion, molecular iodine was
found to be the most effective catalyst in terms of yields
and reaction rates. However, the combination of trieth-
ylsilane and 5 mol % of molecular iodine (Et3SiH/I2)
was found to be equally effective for this conversion. It
is noteworthy that the products were obtained in low
to moderate yields (45–60%) along with deacetylated
glycals when TMSI was employed as the catalyst for this
reaction. The scope and generality of this process is illus-
trated with respect to various glycals and the results are
presented in Table 1.
O
O
AcO
O
AcO
O
I2
O
O
PMHS
AcO
AcO
+
AcO
AcO
CH2Cl2, r.t.
OR
OAc
OAc
OAc
OAc
A feasible mechanism is depicted in Scheme 3. Iodine
reacts initially with PMHS to produce trimethylsilyl
iodide and the unstable reducing reagent 4, which
reduces the glucals.12
2
1i
3i
Scheme 2.

J. S. Yadav et al. / Tetrahedron Letters 46 (2005) 2687–2690
2689
Me
Si
Me
Si
Me
Me
Si
SiMe3
O
O
IO
O
Si
H
Me3SiI +
+
Me3SiO
O
SiMe3
I2
O
n
n
H
H
H
4
Me
Me
Si
Me
Me
Si
O
O
AcO
Me
Si
O
SiMe3
n-1
O
H
O
AcO
AcO
Si
H
SiMe3
n-1
O
O
O
Si
+
AcO
AcO
H
H
Si
O
H
O
OI
I
Me
Me
Me
Me
Me
Si
Si
H
Si
H
SiMe3
n-1
O
IO
O
O
+
OAc
Scheme 3.
8. (a) Tsukiyama, T.; Isobe, M. Tetrahedron Lett. 1992, 33,
7911–7914; (b) Huang, G.; Isobe, M. Tetrahedron 2001,
57, 10241–10246; (c) Tsukiyama, T.; Peters, S. C.; Isobe,
M. Synlett 1993, 413–414; (d) Hosokawa, S.; Kirschbaum,
B.; Isobe, M. Tetrahedron Lett. 1998, 39, 1917–1920.
9. (a) Kartha, K. P. R.; Ballell, L.; Bilke, J.; McNeil, M.;
Field, R. A. J. Chem. Soc., Perkin. Trans. 1 2001, 770–772;
(b) Koreeda, M.; Houston, T. A.; Shull, B. K.; Klemke,
E.; Tuinman, R. J. Synlett 1995, 90–92; (c) Vaino, A. R.;
Szarek, W. A. Synlett 1995, 1157–1158; (d) Lipshutz, B.
H.; Keith, J. Tetrahedron Lett. 1998, 39, 2495–2498.
10. (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem.
Soc., Perkin. Trans. 1 2000, 3082–3084; (b) Yadav, J. S.;
Reddy, B. V. S.; Sabitha, G.; Reddy, G. S. K. K. Synthesis
2000, 1532–1534; (c) Yadav, J. S.; Reddy, B. V. S.; Rao, C.
V.; Rao, K. V. J. Chem. Soc., Perkin. Trans. 1 2002, 1401–
1404.
In summary, we have described the novel use of mole-
cular iodine for the activation of polymethylhydrosil-
oxane and the reaction to produce 3,6-dihydropyrans
from glycals under extremely mild conditions. This
new reagent combination (PMHS/I2) provides a simple
and general method for the preparation of highly func-
tionalized 3,6-dihydropyrans from glycals.
Acknowledgements
B.V.S., K.P.L. and T.S. thank CSIR, New Delhi for the
award of fellowships.
References and notes
11. Experimental procedure: Iodine (2.5 mol %) was added to
a mixture of 3,4,6-tri-O-acetyl-D-glucal 1a (2 mmol) and
polymethylhydrosiloxane (6 mmol) in dichloromethane
(10 mL) the reaction and stirred at room temperature for
3 h. After complete conversion, as indicated by TLC, the
reaction mixture was diluted with water (10 mL) and
extracted with dichloromethane (2 · 15 mL). The organic
layers were dried over anhydrous Na2SO4 and purified by
column chromatography on silica gel (Merck, 100–
200 mesh, ethyl acetate–hexane, 1:9) to afford pure
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27
dihydropyran 3a: liquid, ½aꢀD +84.2 (c 1.25, CHCl3), IR
(KBr): t 3025, 2934, 1773, 1631, 1490, 1427, 1370, 1316,
1197, 1078, 1043, 922, 872, 769 cmꢁ1. 1H NMR (200 MHz,
CDCl3): d 2.09 (s, 6H), 3.60–3.68 (m, 1H), 4.10–4.25 (m,
4H), 5.24 (br d, J = 8.5 Hz, 1H), 5.75 (dd, J = 10.5, 1.5 Hz,
1H), 5.95 (dd, J = 10.5, 1.5 Hz, 1H). 13C NMR (50 MHz,
CDCl3): d 20.5, 21.1, 63.0, 64.5, 65.1, 73.6, 124.0, 129.3,
170.0, 170.6. EIMS: m/z (%): 214 (M+, 12), 155 (100), 145
27
(13), 112 (56), 95 (92). Compound 3g: liquid, ½aꢀD +67.0 (c
5. (a) Danishefsky, S. J.; Allen, J. R. Angew Chem., Int. Ed.
2000, 39, 836–863; (b) Nicolaou, K. C.; Mitchel, H. J.
Angew. Chem., Int. Ed. 2001, 40, 1576–1624.
1.0, CHCl3), IR (KBr): t 2925, 2168, 1261, 1219, 1054,
850, 772 cmꢁ1 1H NMR (200 MHz, CDCl3): d 2.10 (s,
.
3H), 3.75–3.90 (m, 2H), 4.05–4.10 (m, 1H), 4.20–4.25 (m,
1H), 5.05–5.09 (m, 1H), 5.85–5.95 (dd, J = 10.3, 1.7 Hz,
1H), 6.10 (dd, J = 10.3, 1.7 Hz, 1H). 13C NMR (50 MHz,
CDCl3): d 21.0, 64.8, 64.9, 67.6, 122.4, 129.5, 170.6. EIMS:
m/z (%): 143 (M++1, 10), 116 (8), 101 (8), 93 (8), 83 (100),
6. (a) Isobe, M.; Nishizawa, R.; Hosokawa, S.; Nishikawa,
T. Chem. Commun. 1998, 2665–2676; (b) Das, S. K.;
Reddy, K. A.; Abbineni, C.; Roy, J.; Rao, K. L. V. N.;
Sachwani, R. H.; Iqbal, J. Tetrahedron Lett. 2003, 44,
4507–4509.
27
73 (10), 57 (15), 43 (82). Compound 3j: liquid, ½aꢀD +155.0
7. (a) Hosokawa, S.; Isobe, M. Synlett 1995, 1179–1180; (b)
Hosokawa, S.; Isobe, M. Synlett 1996, 351–352.
(c 0.5, CHCl3), IR(KBr): t 2996, 2355, 1765, 1633, 1439,

2690
J. S. Yadav et al. / Tetrahedron Letters 46 (2005) 2687–2690
1376, 1195, 1078, 1015, 923, 863, 775 cmꢁ1
.
1H NMR
EIMS: m/z (%): 503 (M++1, 10), 447 (10), 281 (20), 239
(35), 196 (30), 154 (50), 83 (60), 69 (70), 55 (100), 43 (90).
12. This mechanism is based on the observations that PMHS
on treatment with iodine produced Me3SiI and hydroiodic
acid. However, Me3SiI or HI or Me3SiI–HI when treated
with the glucal acetate in the presence of PMHS did not
give the desired product.
(200 MHz, CDCl3): d 2.05–2.15 (m, 15H), 3.65–3.73 (m,
1H), 3.80–3.90 (m, 1H), 4.15–4.23 (m, 10H), 5.19–5.28 (m,
1H), 5.75 (dd, J = 10.1, 1.6 Hz, 1H), 5.90 (dd, J = 10.1,
1.6 Hz, 1H). 13C NMR (50 MHz, CDCl3): d 20.4, 20.5,
20.6, 20.7, 20.8, 63.3, 63.9, 65.4, 66.2, 68.8, 70.3, 71.1, 76.2,
76.5, 88.5, 124.4, 129.2, 170.0, 170.4, 170.6, 170.7, 170.8.