A highly efficient synthetic protocol for tetrahydropyranylation/ depyranylation of alcohols and phenols

Article abstract of DOI:10.1002/ejoc.200500400

Bismuth(III) nitrate pentahydrate [Bi(NO₃)₃· 5H₂O] is found to be an effective catalyst for both tetrahydropyranylation and depyranylation of alcohols and phenols. Some of the major advantages of this protocol are: non-aqueous workup, good yields, the involvement of a less-expensive and nontoxic catalyst, and compatibility in the presence of a large number of other protecting groups. Notably, isopropylidene, benzylidene, and thioacetal groups are also unaffected under the experimental conditions. Remarkably, a selective mono-protection of diols and primary alcohols can be achieved chemoselectively by employing the same catalyst. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

Full text of DOI:10.1002/ejoc.200500400

FULL PAPER
A Highly Efficient Synthetic Protocol for Tetrahydropyranylation/
Depyranylation of Alcohols and Phenols
Abu T. Khan,*[a] Subrata Ghosh,[a] and Lokman H. Choudhury[a]
Dedicated to Professor K. Dey on the occasion of his 65th birthday
Keywords: Tetrahydropyranylations / Alcohols / Phenols / Bismuth(iii) nitrate pentahydrate / Synthetic methods
Bismuth(III) nitrate pentahydrate [Bi(NO3)3·5H2O] is found to
be an effective catalyst for both tetrahydropyranylation and
depyranylation of alcohols and phenols. Some of the major
advantages of this protocol are: non-aqueous workup, good
yields, the involvement of a less-expensive and nontoxic cat-
alyst, and compatibility in the presence of a large number of
other protecting groups. Notably, isopropylidene, benzyli-
dene, and thioacetal groups are also unaffected under the
experimental conditions. Remarkably, a selective mono-pro-
tection of diols and primary alcohols can be achieved chemo-
selectively by employing the same catalyst.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
been reported that involves a heterogeneous catalyst such
as a solid silica-based sulfonic acid.[19] Further, more meth-
ods have recently been reviewed that employ various hetero-
geneous catalysts.[20] Unfortunately, many of these pro-
cedures have a disadvantage such as harsh reaction condi-
tions, long reaction times, incompatibility with other acid-
sensitive functional groups,[3,9,10,13] the involvement of more
expensive and moisture sensitive reagents, and some also
have to be freshly prepared prior to use.[4,8,9,15,16] As part
of our ongoing research to develop new synthetic method-
ologies by using various new reagents,[21–23] we realized that
there is further scope for a cleaner and greener methodol-
ogy for tetrahydropyranylation/depyranylation, one that
might work under mild catalytic conditions and that is eco-
nomically cheaper. In recent years, bismuth compounds
have been gaining interest in various organic transforma-
tions.[24,25] We thought that bismuth(iii) nitrate pentahy-
drate, which is commercially available at a very low cost
and is relatively nontoxic, might be a useful catalyst for
tetrahydropyranylation/depyranylation. So far, bismuth(iii)
nitrate pentahydrate has been utilized in various organic
transformations: i) acetylation and benzoylation of alcohols
and phenols,[26a] ii) guanidylation of N-benzoylthiourea,[26b]
iii) conversion of thiocarbonyl compounds to the corre-
sponding carbonyl compounds,[26c] iv) Michael reaction,[26d]
v) oxidation of thiols to disulfides,[26e] and vi) for the syn-
thesis of acylals[26f] and dihydropyrimidinone.[26g] In this
paper, we report the tetrahydropyranylation of alcohols and
phenols and depyranylation in the presence of catalytic
amounts of bismuth(iii) nitrate pentahydrate, as shown in
Scheme 1.
Introduction
The protection/deprotection strategy is a very common
practice for manipulation of other functional groups during
multistep organic synthesis. Among various functional
groups, the protection of the hydroxy group as tetra-
hydropyranyl (THP) ether is usually preferred because of
its low cost, ease of preparation, and stability of THP ethers
towards metal hydrides, and acylating, alkylating, Grig-
nard, and organometallic reagents.[1] Sometimes THP
ethers also serve as a stable protecting groups in peptide,
nucleoside and nucleotide, carbohydrate, and steroid chem-
istry. Tetrahydropyranylation of alcohols or phenols is usu-
ally achieved by using pTsA,[2] BF3·OEt2,[3] or PPTS.[4]
Many other reagents, such as ZrCl4,[5] I2,[6] LiBr,[7] acetonyl-
triphenylphosphonium bromide (ATPB),[8] TBATB,[9] alu-
minium chloride hexahydrate,[10] LiOTf,[11] In(OTf)3,[12] di-
alkylimidazolium tetrachloroaluminates,[13] InCl3 immobi-
[15]
lized in ionic liquids,[14] Bi(OTf)3, bromodimethylsulfon-
ium bromide,[16] cupric sulfate pentahydrate,[17] and
NbCl5,[18] have also been employed for both tetrahydropy-
ranylation/depyranylation in recent years. Though metal tri-
flates have been found to be effective catalysts for the above
transformations, they still have some drawbacks, such as
they are relatively expensive, difficult to handle, and not
readily available. They also require harsh[11] and inert reac-
tion conditions.[15] Very recently, one more method has
[a] Department of Chemistry, Indian Institute of Technology Gu-
wahati,
Guwahati-781 039, India
Eur. J. Org. Chem. 2005, 4891–4896
DOI: 10.1002/ejoc.200500400
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4891

A. T. Khan, S. Ghosh, L. H. Choudhury
FULL PAPER
corresponding THP ethers in good yields, as shown in
Table 1. The formation of the products was confirmed by
IR, 1H- and 13C NMR spectroscopy and by elemental
analysis. In addition, we have also compared some of the
spectroscopic data with that obtained by a method reported
earlier.[28]
The most significant advantage of this protocol is that
various symmetric diols can be chemoselectively protected
when transformed into the mono THP ethers (2gЈ–kЈ) [with
5–10% di-THP ethers] by using 5 mol-% catalyst under
identical conditions; this is sometimes difficult to achieve
Scheme 1.
Results and Discussion
When a mixture of 1-decanol (entry 1a) and 3,4-dihydro- with other methods, see Table 2. It should also be noted
2H-pyran (DHP) in dichloromethane was treated with that primary alcohols can be protected chemoselectively in
5 mol-% of bismuth(iii) nitrate pentahydrate, it was the presence of a secondary alcohol (entry 1lЈ). An ad-
smoothly converted into the corresponding THP ether 2a ditional feature of our protocol is that tetrahydropyranyl-
within 15 min in 92% yield. Similarly, 2-phenylethanol (en- ation can be carried out even on a large scale (for example,
try 1b) was converted into the corresponding THP ether on 10–100 mmol) without any difficulty.
2b in fairly good yield under identical reaction conditions.
The formation of the product can be explained as fol-
Various benzylic alcohols (entries 1c–g), allyl alcohols (en- lows. We believe that the actual catalyst is nitric acid, which
try 1h), secondary alcohols (entries 1i–l), and tertiary is generated from bismuth(iii) nitrate pentahydrate in the
alcohols (entries 1m and 1n) were smoothly converted into reaction medium. This fact is verified in two ways: i) the
the corresponding THP ethers 2c–n, respectively, in very tetrahydropyranylation of 4-nitrobenzyl alcohol (entry 1d)
good yields, as shown in Table 1. Here, it is worth men- in the presence of bismuth(iii) nitrate pentahydrate
tioning that our procedure is more highly efficient in terms (0.05 mmol) and potassium carbonate (1 mmol) did not
of reaction times and yields than some of the recently re- show the formation of any product; ii) the formation of
ported procedures.[15,18] For example, tetrahydropyranyl- THP ether 2d from 4-nitrobenzyl alcohol is possible in 72%
ation of 4-nitrobenzylalcohol (entry 1d), geraniol (entry 1h), yield in the presence of a catalytic amount of concentrated
and (–)menthol (entry 1k) to form the corresponding THP HNO3. However, Banik et al. reported[26d] while studying
ethers was completed much more quickly and also provided Michael reactions that bismuth(iii) nitrate pentahydrate acts
better yields than the bismuth triflate method.[15] We were only as a Lewis acid because they did not observe any
then interested in whether the same catalyst could be em- Michael addition product in the presence of other metal
ployed for tetrahydropyranylation of phenolic compounds. nitrates that can readily generate nitric acid in the medium.
By following identical reaction procedures, various phenols
Notably, the same catalyst can be used for depyranyl-
(entries 1o–q) were smoothly converted into the corre- ation reactions. For example, the THP ether 2b undergoes
sponding THP ethers 2o–q in good yields. It had been ob- cleavage in methanol within 45 min in 82% yield with
served previously that the formation of the THP ether 2q 5 mol-% of catalyst. Likewise, various THP ethers 2c, 2f,
from β naphthol (entry 1q) by employing Bi(OTf)3 as cata- 2n, 2r, and 2z were converted into the parent hydroxyl com-
lyst was a failure,[15] whereas we have shown that it can be pounds 1c, 1f, 1n, 1r, and 1z, respectively, within 35–50 min
easily accessible by our method; this offers an additional in 80–90% yields under similar reaction conditions, which
advantage. We then turned our attention on whether the are given in the Experimental Section.
same catalyst could be useful for tetrahydropyranylation of
The efficiency and generality of the present method can
substrates containing other protecting groups. We observed be realized at a glance by comparing our results with those
that various protected alcohols (entries 1r–x) containing of some recently reported procedures (shown in Table 3).
protecting groups such as acetyl, benzyl, benzoyl, trityl, to- The results have been compared with respect to the reaction
syl, TBS and TBDPS ethers were smoothly converted into times, mol-% of the catalyst used, and yields. Here we have
the corresponding THP ethers 2r–x without affecting the chosen some of the substrates as model substrates. In case
other protecting groups. Furthermore, substrates with of entry 1, the yields are comparable, but the reaction time
thioacetal groups (entries 1y and 1z), and isopropylidene proves the efficiency of our protocol. For entry 2, the de-
protected alcohols (entries 1aЈ and 1bЈ) and benzylidene sired THP ether 2q was difficult to obtain when Bi(OTf)3·
protected diol (entry 1cЈ) can be easily transformed into the 4H2O was used, but it can be prepared in good yield and
desired THP ethers in good yields as shown in the Table 1. without any difficulty by employing our protocol. For en-
Interestingly, it should be noted that the formation of THP tries 3, 4 and 5, the yields are better and reaction times are
ethers 2y and 2z from the compounds 1y and 1z, respec- lower when our protocol is used. The protocol with
tively, was difficult by our recently reported procedure, Bi(OTf)3·4H2O requires not only an inert atmosphere, but
where we used cupric sulfate pentahydrate as catalyst.[17] also Bi(OTf)3·4H2O has to be prepared prior to use. There-
Remarkably, by employing our current protocol, various fore, considering all these facts we believe that bismuth(iii)
carbohydrates (entries 1dЈ and 1eЈ), as well as a nucleoside nitrate pentahydrate is a relatively better catalyst for tetra-
compound (entry 1fЈ), were smoothly converted into the hydropyranylation of hydroxyl compounds.
4892
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4891–4896

Tetrahydropyranylation/Depyranylation of Alcohols and Phenols
FULL PAPER
Table 1. Tetrahydropyranylation of alcohols and phenols in the
presence of a catalytic amount of bismuth(iii) nitrate pentahydrate
[Bi(NO3)3·5H2O].
Table 2. Selective tetrahydropyranylation of diols using a catalytic
amount of Bi(NO3)3·5H2O.
[a] All starting materials and final products were characterized by
IR, 1H NMR, and 13C NMR spectroscopy and by elemental analy-
sis. [b] Isolated yield.
Table 3. Comparison of results of tetrahydropyranylation of
alcohols and phenols with other catalysts.
Conclusions
In conclusion, the present methodology demonstrates
Bi(NO3)3·5H2O as an effective catalyst for tetrahydropy-
ranylation/depyranylation of alcohols and phenols. The
main advantages of this method are: mild, clean and simple
reaction conditions, good yields, nonaqueous workup, and
environmentally benign reagents. In addition, our method-
ology might be useful for substrates containing a wide vari-
ety of other protecting groups. Furthermore, this method is
also expected to have much better application in organic
synthesis because of the very low cost and nontoxic nature
of the reagent. We believe this methodology will be a valu-
able addition to modern synthetic methodologies.
Experimental Section
Melting points were recorded on a Büchi B-545 melting point appa-
ratus and are uncorrected. IR spectra were recorded in KBr or neat
on a Nicolet Impact 410 spectrophotometer. 1H NMR and 13C
NMR spectra were recorded on a Bruker 200 MHz, Bruker
300 MHz, and Jeol 400 MHz spectrometer in CDCl3 by using TMS
as internal reference. Elemental analyses were carried out with a
Perkin–Elmer 2400 automatic carbon, hydrogen, nitrogen, and sul-
fur analyzer. Column chromatographic separations were done on
SRL silica gel (60–120 mesh).
[a] All starting materials and final products were characterized by
IR, 1H NMR, and 13C NMR spectroscopy and by elemental analy-
sis. [b] Isolated yield. [c] The reference refers to the spectroscopic
data for the particular compound.
Eur. J. Org. Chem. 2005, 4891–4896
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4893

A. T. Khan, S. Ghosh, L. H. Choudhury
FULL PAPER
Typical Procedure for Tetrahydropyranylation: Bismuth(iii) nitrate
2q: Yield: 0.169 g, 74%. M.p. 44–46 °C. IR (KBr): 3056, 2941,
pentahydrate (0.024 g, 0.05 mmol) was added to a mixture of 1617, 1599, 1510, 1466, 1390, 1253, 1217, 1173, 1037 cm–1. 1H
alcohol or phenol (1 mmol) and 3,4-dihydro-2H-pyran (109 μL,
1.2 mmol) in dichloromethane (2 mL). The mixture was stirred at
room temperature. After completion of the reaction as confirmed
by TLC, the reaction mixture was reduced to approximately 1 mL,
and then it was passed through a short basic alumina column to
afford the desired THP ether.
NMR (300 MHz, CDCl3): δ = 1.60–1.73 (m, 3 H), 1.89–1.92 (m, 2
H), 1.99–2.08 (m, 1 H), 3.62–3.66 (m, 1 H), 3.91–3.97 (m, 1 H),
5.56 (t, J = 3.3 Hz, 1 H), 7.21–7.25 (m, 1 H), 7.32 (d, J = 8.0 Hz,
1 H), 7.39–7.43 (m, 2 H), 7.72–7.76 (m, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 18.7, 25.2, 30.4, 61.9, 96.4, 110.4, 119.1,
123.8, 126.2, 127.0, 127.5, 129.2, 129.4, 134.5, 154.8 ppm.
C15H16O2 (228.29): calcd. C 78.92, H 7.06; found C 78.71, H
6.98%.
2b: Yield: 0.173 g, 84%. IR (Neat): 2942, 2869, 1600, 1465, 1357,
1
1127, 1038 cm–1. H NMR (400 MHz, CDCl3): δ = 1.47–1.82 (m,
2r: Yield: 0.191 g, 83%. IR (neat): 2945, 2873, 1471, 1460, 1439,
1372, 1250, 1034 cm–1. 1H NMR (400 MHz, CDCl3): 1.39–1.84 (m,
12 H), 2.04 (s, 3 H), 3.36–3.41 (m, 1 H), 3.48–3.51 (m, 1 H), 3.71–
3.76 (m, 1 H), 3.82–3.88 (m, 1 H), 4.06 (t, J = 6.8 Hz, 2 H), 4.56–
4.58 (m, 1 H) ppm. C12H22O4 (230.30): calcd. C 62.58, H 9.63;
found C 62.72, H 9.57%.
6 H), 2.91 (t, J = 7.2 Hz, 2 H), 3.41–3.47 (m, 1 H), 3.61 (dt, J =
7.2, J = 4.0, 10.0 Hz, 1 H), 3.72–3.77 (m, 1 H), 3.94 (dt, J = 7.6,
5.2, 9.6 Hz, 1 H), 4.58 (t, J = 3.5 Hz, 1 H), 7.16–7.28 (m, 5 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 19.6, 25.6, 30.8, 36.5, 62.2,
68.3, 98.7, 126.0, 128.1 (2 C), 128.9 (2 C), 140.0 ppm. C13H18O2
(206.28): calcd. C 75.69, H 8.79; found C 75.43, H 8.73%.
2t: Yield: 0.291 g, 87%. IR (neat): 2930, 2857, 1719, 1453, 1276,
2c: Yield: 0.247 g, 91%. IR (Neat): 2942, 2865, 1595, 1465, 1357,
1130, 1075, 1038 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.53–1.87
(m, 6 H), 3.50–3.56 (m, 1 H), 3.85–3.91 (m, 1 H), 4.44 (d, J =
12.4 Hz, 1 H), 4.66–4.68 (m, 1 H), 4.71 (d, J = 12.0 Hz, 1 H), 7.23
(d, J = 8.8 Hz, 2 H), 7.46 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 19.4, 25.5, 30.6, 62.2, 68.0, 97.7, 121.2,
129.2 (2 C), 131.3 (2 C), 137.2 ppm. C12H15O2Br (271.15): calcd.
C 53.16, H 5.58; found C 53.24, H 5.49%.
1
1217, 1114, 1038 cm–1. H NMR (400 MHz, CDCl3): (mixture of
diastereomers): δ = 1.36–1.86 (m, 18 H), 3.35–3.41 (m, 1 H), 3.50–
3.56 (m, 1 H), 3.70–3.78 (m, 1 H), 3.86–3.89 (m, 1 H), 4.31 (t, J =
6.8 Hz, 2 H), 4.56–4.60 (m, 0.5 H), 4.94–4.98 (m, 0.5 H), 7.43 (t, J
= 7.2 Hz, 2 H), 7.55 (t, J = 7.2 Hz, 1 H), 8.04 (d, J = 8.4 Hz, 2 H)
ppm. C20H30O4 (334.45): calcd. C 71.83, H 9.04; found C 71.56, H
9.10%.
2u: Yield: 0.291 g, 81%. IR (neat): 2950, 2868, 1598, 1496, 1450,
2d: Yield: 0.213 g, 90%. IR (Neat): 2943, 2869, 1605, 1522, 1346,
1202, 1127, 1036 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.52–1.92
(m, 6 H), 3.51–3.59 (m, 1 H), 3.86–3.92 (m, 1 H), 4.61 (d, J =
13.6 Hz, 1 H), 4.73–4.74 (m, 1 H), 4.89 (d, J = 13.2 Hz, 1 H), 7.53
(d, J = 9.2 Hz, 2 H), 8.20 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 19.4, 25.4, 30.5, 62.3, 67.6, 98.2, 123.4 (2
C), 127.6 (2 C), 145.9, 147.3 ppm. C12H15NO4 (237.25): calcd. C
60.75, H 6.37, N 5.90; found C 60.54, H 6.29, N 5.78%.
1
1332, 1163, 1071, 1030 cm–1. H NMR (400 MHz, CDCl3): (mix-
ture of diastereomers): δ = 1.38–1.83 (m, 12 H), 3.02 (t, J = 6.6 Hz,
2 H), 3.31–3.36 (m, 1 H), 3.45–3.50 (m, 1 H), 3.66–3.69 (m, 1 H),
3.80–3.86 (m, 1 H), 4.50–4.52 (m, 0.3 H), 4.90–4.92 (m, 0.7 H),
7.15–7.28 (m, 12 H), 7.39–7.41 (m, 3 H) ppm. C29H34O3 (430.58):
calcd. C 80.90, H 7.96; found C 80.66, H 7.89%.
2v: Yield: 0.295 g, 86%. IR (neat): 2945, 2868, 1603, 1465, 1362,
1183, 1132, 1081, 1050, 968, 963 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.40–1.70 (m, 12 H), 2.45 (s, 3 H), 3.32–3.35 (m, 1 H),
3.49–3.50 (m, 1 H), 3.68–3.70 (m, 1 H), 3.80–3.89 (m, 1 H), 4.03
(t, J = 6.8 Hz, 2 H), 4.53–4.54 (m, 1 H), 7.34 (d, J = 8.0 Hz, 2 H),
7.78 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
19.7, 21.7, 22.3, 25.5, 28.8, 29.1, 30.8, 62.4, 67.1, 70.5, 98.8, 127.7
(2 C), 129.6 (2 C), 133.0, 144.5 ppm. C17H26O5S (342.45): calcd. C
59.63, H 7.65, S 9.36; found C 59.40, H 7.71, S 9.15%.
2l: Yield: 0.193 g, 90%. IR (neat): 2935, 2873, 1460, 1347, 1204,
1132, 1030 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.83 (t, J =
7.3 Hz, 3 H), 0.90 (t, J = 7.3 Hz, 3 H), 1.25–1.31 (m, 6 H), 1.39–
1.83 (m, 10 H), 3.42–3.56 (m, 2 H), 3.85–3.91 (m, 1 H), 4.61–4.63
(m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 9.1, 14.0, 19.7,
22.6, 24.7, 25.8, 31.1, 32.1, 32.9, 34.3, 62.6, 78.0, 97.2 ppm.
C13H26O2 (214.35): calcd. C 72.85, H 12.23; found C 72.78, H
12.19%.
2w: Yield: 0.300 g, 87%. IR (neat): 2937, 2860, 1465, 1358, 1254,
2m: Yield: 0.148 g, 65%. IR (neat): 2945, 2863, 1460, 1378, 1281,
1
1106, 1031 cm–1. H NMR (400 MHz, CDCl3): δ = 0.04 (s, 6 H),
1
1204, 1132, 1086, 1030, 994 cm–1. H NMR (400 MHz, CDCl3): δ
0.89 (s, 9 H), 1.25–1.30 (m, 6 H), 1.48–1.87 (m, 12 H), 3.34–3.40
(m, 1 H), 3.47–3.50 (m, 1 H), 3.59 (t, J = 6.4 Hz, 2 H), 3.69–3.73
(m, 1 H), 3.84–3.89 (m, 1 H), 4.56–4.57 (m, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = –5.3 (2 C), 18.3, 19.6, 25.5, 25.7, 25.9 (3
C), 26.1, 29.3, 29.4, 29.7, 30.7, 32.8, 62.2, 63.2, 67.6, 98.8 ppm.
C19H40O3Si (344.61): calcd. C 66.22, H 11.70; found C 66.46, H
11.62%.
= 0.84 (t, J = 6.8 Hz, 3 H), 0.89 (t, J = 7.2 Hz, 3 H), 1.15 (s, 3 H),
1.26–1.39 (m, 6 H), 1.41–1.84 (m, 10 H), 3.42–3.45 (m, 1 H), 3.93–
3.97 (m, 1 H), 4.70 (br. s, 1 H) ppm. C14H28O2 (228.37): calcd. C
73.63, H 12.36; found C 73.84, H 12.27%.
2n: Yield: 0.180 g, 76%. IR (neat): 2935, 2858, 1440, 1245, 1204,
1
1158, 1132, 1068, 1046, 979 cm–1. H NMR (400 MHz, CDCl3): δ
= 1.47–1.54 (m, 4 H), 1.56–1.66 (m, 8 H), 1.76–1.85 (m, 6 H), 2.12
(s, 3 H), 3.40–3.48 (m, 1 H), 3.91–3.99 (m, 1 H), 4.82–4.85 (m, 1 H)
ppm. C15H24O2 (236.35): calcd. C 76.23, H 10.23; found C 76.03, H
10.29%.
2x: Yield: 0.399 g, 85%. IR (neat): 2935, 2858, 1475, 1440, 1388,
1363, 1204, 1112, 1030, 979 cm–1. 1H NMR (200 MHz, CDCl3):
(mixture of diastereomers): δ = 1.04 (s, 9 H), 1.10–1.35 (m, 8 H),
1.52–1.85 (m, 10 H), 3.35–3.54 (m, 2 H), 3.64 (t, J = 6.4 Hz, 2 H),
3.70–3.92 (m, 2 H), 4.52–4.62 (m, 0.4 H), 4.90–5.00 (m, 0.6 H),
7.30–7.46 (m, 6 H), 7.61–7.71 (m, 4 H) ppm. C29H44O3Si (468.75):
calcd. C 74.31, H 9.46; found C 74.09, H 9.40%.
2p: Yield: 0.179 g, 87%. IR (neat): 2945, 2858, 1696, 1609, 1511,
1358, 1306, 1250, 1209, 1163, 1112, 1040 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 1.49–1.78 (m, 4 H), 1.81–1.99 (m, 2 H),
3.57–3.62 (m, 1 H), 3.80–3.86 (m, 1 H), 5.47–5.51 (m, 1 H), 7.12
2y: Yield: 0.235 g, 83%. IR (neat): 2930, 1614, 1511, 1255, 1240,
(d, J = 8.8 Hz, 2 H), 7.79 (d, J = 8.8 Hz, 2 H), 9.84 (s, 1 H) ppm. 1122, 1040 cm–1. H NMR (300 MHz, CDCl3): δ = 1.46–2.00 (m,
1
13C NMR (100 MHz, CDCl3): δ = 18.4, 24.9, 30.6, 62.0, 96.0, 116.4
(2 C), 131.8 (2 C), 132.3, 162.1, 191.1 ppm. C12H14O3 (206.24):
calcd. C 69.89, H 6.84; found C 69.78, H 6.78%.
6 H), 3.31–3.41 (m, 2 H), 3.48–3.63 (m, 3 H), 3.89–3.93 (m, 1 H),
5.41 (t, J = 3.0 Hz, 1 H), 5.64 (s, 1 H), 7.00 (d, J = 8.8 Hz, 2 H),
7.44 (d, J = 8.7 Hz, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
4894
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 4891–4896

Tetrahydropyranylation/Depyranylation of Alcohols and Phenols
19.1, 25.6, 30.7, 40.6 (2 C), 56.5, 62.4, 96.7, 116.8 (2 C), 129.8 (2
FULL PAPER
1.51–1.63 (m, 3 H), 1.67–1.89 (m, 3 H), 2.25 (br. s, 1 H, D2O ex-
C), 133.1, 157.3 ppm. C14H18O2S2 (282.41): calcd. C 59.54, H 6.42, changeable), 3.48–3.61 (m, 2 H), 3.78 (t, J = 5.2 Hz, 2 H), 3.83–3.95
S 22.70; found C 60.05, H 6.39, S 22.54%.
(m, 2 H), 4.57–4.59 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 19.8, 25.4, 30.7, 32.1, 61.5, 62.6, 66.3, 99.1 ppm. C8H16O3
(160.21): calcd. C 59.98, H 10.07; found C 60.05, H 10.12.
2z: Yield: 0.359 g, 81%. IR (neat): 2966, 2925, 2843, 1619, 1516,
1450, 1327, 1260, 1178, 1086, 1030 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.53–1.87 (m, 12 H), 2.70–2.80 (m, 2 H), 2.92–2.98
(m, 2 H), 3.45–3.60 (m, 4 H), 3.85–3.88 (m, 4 H), 3.88 (s, 3 H),
4.85–4.95 (m, 2 H), 6.22 (s, 1 H), 7.00 (d, J = 8.8 Hz, 2 H), 7.84
(d, J = 8.0 Hz, 2 H) ppm. C22H34O5S2 (442.63): calcd. C 59.70, H
7.74, S 14.49; found C 59.56, H 7.67, S 14.32%.
2jЈ: Yield: 0.173 g, 75%. IR (neat): 3422, 2931, 2858, 1454, 1354,
1276, 1127, 1030 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.30–1.40
(br. s, 8 H), 1.50–1.61 (m, 6 H), 1.69–174 (m, 2 H), 1.80–1.90 (m,
2 H), 2.05 (br. s, 1 H, D2O exchangeable), 3.35–3.41 (m, 1 H), 3.48–
3.51 (m, 1 H), 3.64 (t, J = 6.8 Hz, 2 H), 3.70–3.74 (m, 1 H), 3.84–
3.89 (m, 1 H), 4.56–4.58 (m, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 19.7, 25.5, 25.7, 26.2, 29.3, 29.4, 29.7, 30.7, 32.7, 62.2,
62.7, 67.6, 98.7 ppm. C13H26O3 (230.35): calcd. C 67.79, H 11.38;
found C 67.65, H 11.29.
2bЈ: Yield: 0.272 g, 79%. IR (neat): 2945, 1470, 1388, 1271, 1230,
1076, 1009 cm–1. 1H NMR (400 MHz, CDCl3): (mixture of dia-
stereomers): δ = 1.28 (s, 3 H), 1.29 (s, 3 H), 1.39 (s, 3 H), 1.49 (s,
3 H), 1.50–1.82 (m, 6 H), 3.43–3.49 (m, 1 H), 3.56–3.85 (m, 2 H),
3.93–3.98 (m, 1 H), 4.20 (dd, J = 1.7, 7.8 Hz, 1 H), 4.23–4.29 (m,
1 H), 4.52–4.61 (m, 2 H), 4.88 (d, J = 4.9 Hz, 1 H), 5.48 (dd, J =
5.2, 9.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.4,
19.5, 19.7 (2 C), 24.4, 24.5, 24.9, 25.4 (2 C), 25.9, 26.0, 30.5, 30.7
(2 C), 62.2, 62.4, 62.9, 65.9, 66.1, 66.5, 67.4, 70.5, 70.6, 70.7, 71.0,
71.4, 94.6, 96.3, 96.4, 99.0, 99.1, 108.5, 109.1, 109.2 ppm. C17H28O7
(344.40): calcd. C 59.29, H 8.19; found C 59.52, H 8.23%.
2kЈ: Yield: 0.106 g, 62%. IR (neat): 3411, 2945, 2863, 1450, 1393,
1
1358, 1271, 1127, 1020 cm–1. H NMR (400 MHz, CDCl3): 1.52–
1.85 (m, 7 H), 3.53–3.56 (m, 1 H), 3.81–3.86 (m, 1 H), 4.23–4.37
(m, 4 H), 4.81 (t, J = 3.2 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 19.4, 25.7, 30.6, 51.5, 54.7, 62.3, 82.1, 84.6, 97.2 ppm.
C9H14O3 (170.21): calcd. C 63.51, H 8.29; found C 63.64, H 8.24.
2lЈ: Yield: 0.148 g, 76%. IR (neat): 3416, 2940, 2873, 1445, 1393,
1265, 1204, 1132, 1081, 1035, 979 cm–1. 1H NMR (400 MHz,
CDCl3): (mixture of diastereomers): δ = 1.52–1.83 (m, 6 H), 3.27–
3.37 (br. s, 1 H, D2O exchangeable), 3.51–3.99 (m, 7 H), 4.51–4.53
(m, 0.5 H), 4.57–4.59 (m, 0.5 H) ppm.13C NMR (100 MHz,
CDCl3): δ = 20.3, 20.6, 25.5, 25.6, 31.0, 31.1, 45.8, 46.2, 63.5, 64.0,
70.1, 70.5, 70.8 (2 C), 100.4, 100.9 ppm. C8H15O3Cl (194.66): calcd.
C 49.36, H 7.77; found C 49.52, H 7.84.
2cЈ: Yield: 0.288 g, 60%. IR (neat): 2935, 2858, 1634, 1470, 1383,
1265, 1086, 1030, 974 cm–1. 1H NMR (400 MHz, CDCl3): (mixture
of diastereomers): δ = 1.33 (t, J = 7.6 Hz, 3 H), 1.42–1.76 (m, 12
H), 2.63–2.67 (m, 2 H), 3.23–3.67 (m, 7 H), 3.90–4.00 (m, 1 H),
4.22–4.27 (m, 1 H), 4.38–4.48 (m, 3 H), 4.64–4.70 (m, 1 H), 5.44
(s, 1 H), 7.21–7.27 (m, 3 H), 7.34–7.38 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 15.04, 15.16, 19.03, 19.63, 20.03, 21.13,
24.44, 24.87, 25.22, 25.44, 29.03, 30.69, 31.00, 65.40, 65.63, 66.96,
68.65, 70.09, 70.83, 72.15, 73.29, 79.34, 80.57, 83.97, 84.20, 84.87,
86.23, 101.24, 101.72, 102.35, 102.79, 125.98, 126.33, 128.21,
137.28 ppm. C25H36SO7 (480.62): calcd. C 62.48, H 7.55, S 6.67;
found C 62.71, H 7.59, S 6.62
Typical Procedure for Depyranylation: Bismuth(iii) nitrate pentahy-
drate (0.024 g, 0.05 mmol) was added into a stirred solution of the
THP ether of 4-bromobenzyl alcohol 2c (0.271 g, 1 mmol) in meth-
anol (2 mL) at room temperature. The reaction was complete
within 40 min, and the mixture was concentrated in rotavapor. The
crude residue was purified through a short silica gel column. The
desired 4-bromobenzyl alcohol (1c) was obtained (0.170 g) in 91%
yield.
2dЈ: Yield: 0.493 g, 79%. IR (neat): 2935, 2858, 1634, 1470, 1383,
1265, 1086, 1030, 974 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.41–
1.94 (m, 6 H), 3.49–4.15 (m, 10 H), 4.51–4.96 (m, 7 H), 5.20–5.30
(m, 1 H), 7.15–7.40 (m, 20 H) ppm. C39H44O7 (624.77): calcd. C
74.98, H 7.10; found C 74.73, H 7.01
2eЈ: Yield: 0.473 g, 84%. IR (neat): 2941, 2873, 1453, 1354, 1202,
Acknowledgments
1
1074, 1033 cm–1. H NMR (400 MHz, CDCl3): δ = 1.43–1.95 (m,
6 H), 2.47 (t, J = 6.0 Hz, 1 H, 4-H), 3.39 (s, 3 H), 3.40–4.02 (m,
11 H), 4.47–4.77 (m, 5 H), 4.95–5.02 (m, 1 H), 7.24–7.37 (m, 15 H)
ppm. C34H42O7 (562.70): calcd. C 72.57, H 7.52; found C 72.63, H
7.48.
A. T. K. thanks the DST, New Delhi for a financial grant (Grant
No. SP/S1/G-35/98), S. G. is grateful to IITG and L. H. C. is thank-
ful to CSIR for their research fellowships. We are thankful to the
Director, IIT Guwahati for the general facilities to carry out the
research work. We are thankful to Prof. G. Sundararajan, Depart-
ment of Chemistry, IIT Madras and Dr. N. G. Ramesh, Depart-
2fЈ: Yield: 0.306 g, 83%. IR (neat): 3235, 3109, 2966, 2935, 2817,
1788, 1690, 1481, 1409, 1271, 1209, 1107, 1055, 989 cm–1. 1H NMR
(400 MHz, CDCl3): (mixture of diastereomers): δ = 1.33 (s, 3 H),
1
ment of Chemistry, IIT Delhi for recording some of the H NMR
1.34 (s, 3 H), 1.49 (s, 3 H), 1.51 (s, 3 H), 1.47–1.90 (m, 12 H), 3.49– and 13C NMR spectra. We are very grateful to referees for their
3.57 (m, 4 H), 3.65 (dd, J = 2.4, 11.2 Hz, 1 H), 3.78–3.83 (m, 2 H),
3.94 (dd, J = 3.2, 11.2 Hz, 1 H), 4.01–4.05 (m, 2 H), 4.37–4.42 (m,
1 H), 4.57–4.59 (m, 1 H), 4.73–4.74 (m, 1 H), 4.81–4.82 (m, 1 H),
4.87–4.88 (m, 1 H), 4.89–4.95 (m, 1 H), 5.64 (d, J = 8.0 Hz, 1 H),
5.66 (d, J = 8.0 Hz, 1 H), 5.88 (d, J = 2.4 Hz, 1 H), 5.90 (d, J =
2.4 Hz, 1 H), 7.61 (d, J = 8.0 Hz, 1 H), 7.65 (d, J = 8.0 Hz, 1 H),
8.58 (br. s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.01,
20.84, 25.56, 25.58, 25.62, 25.78, 25.84, 27.64, 30.81, 32.42, 63.05,
63.11, 64.22, 67.52, 67.78, 80.99, 81.20, 85.45, 85.68, 85.91, 92.89,
94.85, 99.22, 99.84, 102.05, 102.33, 114.24, 114.44, 140.88, 141.48,
150.46 (2 C), 163.86 (2 C) ppm. C17H24 N2O7 (368.38): calcd. C
55.43, H 6.57, N 7.60; found C 55.61, H 6.59, N 7.53.
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Eur. J. Org. Chem. 2005, 4891–4896
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4895

A. T. Khan, S. Ghosh, L. H. Choudhury
FULL PAPER
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Published Online: October 4, 2005
4896
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Eur. J. Org. Chem. 2005, 4891–4896