Solvent-free carbon-oxygen bond formation catalysed by CeCl 3·7H2O/NaI: Tetrahydropyranylation of hydroxy groups

Article abstract of DOI:10.1002/ejoc.200500780

An efficient and highly chemoselective method fo the protection of free hydroxy compounds with 3,4-dihydro-2H-pyran is reported. Since the deprotection of THP-ethers occurs very readily at room temperature, the successful use of this type of protecting group depends only upon how readily it can be introduced. For this we have examined the tetrahydropyranylation of alcohols and phenols catalysed by the CeCl₃·7H₂O/NaI system surface under solvent-free conditions. The reaction presents the advantage of being performable under extremely mild conditions by use of catalytic amounts of an interesting Lewis acidic system consisting of the CeCl₃· 7H₂O/NaI catalyst combination, which can be easily separated from the reaction mixture. The advantages of this procedure, which utilizes cheap and "lfriendly" reagents, over the previously reported ones are discussed. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500780

FULL PAPER
DOI: 10.1002/ejoc.200500780
Solvent-Free Carbon–Oxygen Bond Formation Catalysed by CeCl3·7H2O/NaI:
Tetrahydropyranylation of Hydroxy Groups
Giuseppe Bartoli,*[b] Riccardo Giovannini,[c] Arianna Giuliani,[a] Enrico Marcantoni,*[a]
Massimo Massaccesi,[a] Paolo Melchiorre,[b] Melissa Paoletti,[a] and Letizia Sambri[b]
Keywords: Alcohols / Cerium / Lewis acids / Chemoselectivity / Synthetic methods / Protecting groups
An efficient and highly chemoselective method fo the protec-
tion of free hydroxy compounds with 3,4-dihydro-2H-pyran
is reported. Since the deprotection of THP-ethers occurs very
readily at room temperature, the successful use of this type
of protecting group depends only upon how readily it can be
introduced. For this we have examined the tetrahydropy-
ranylation of alcohols and phenols catalysed by the
CeCl3·7H2O/NaI system surface under solvent-free condi-
tions. The reaction presents the advantage of being perform-
able under extremely mild conditions by use of catalytic
amounts of an interesting Lewis acidic system consisting of
the CeCl3·7H2O/NaI catalyst combination, which can be eas-
ily separated from the reaction mixture. The advantages of
this procedure, which utilizes cheap and “friendly” reagents,
over the previously reported ones are discussed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
thetically useful as building blocks for the synthesis of bio-
logically important substances[6] and can also be used in
perfume formulations.[7]
Introduction
As part of our research program on the development of
new and general strategies for the synthesis of biologically
important natural and unnatural substances, we have been
involved with chemoselective transformations of polyfunc-
tional compounds with the aid of protecting groups.[1] The
protection of alcohols and phenols plays a key role in the
synthesis of polyfunctional organic molecules. Numerous
naturally occurring and synthetically and biologically inter-
esting compounds such as nucleosides, carbohydrates, car-
bocycles, steroids, and alkaloids include hydroxy functions
as parts of their structures[2] and several reactions of these
compounds need some protection of their hydroxy groups
in order to increase yields and to reduce undesired side re-
actions. Although over 150 hydroxy-protecting groups have
been reported, few have found wide applications.[3] Novel
OH protections are thus required as molecular targets in-
crease in complexity and new fields such as supported-oli-
gosaccharide synthesis emerge.[4] Tetrahydropyranyl (THP)
ethers are frequently employed as protecting groups for hy-
droxy functionalities in multistep synthesis, thanks both to
their ease of preparation and stability under a wide variety
of reaction conditions and their subsequent ease of re-
moval.[5] Furthermore, tetrahydropyranyl ethers are syn-
Acid-catalysed addition of alcohols and phenols to 3,4-
dihydro-2H-pyran (DHP, 2) in an organic solvent at room
temperature is a useful procedure in organic synthesis
(Scheme 1). When Brønsted acids[8] are used, incompatibil-
ity with other functions in the molecules is observed, and
in many instances the reaction does not go to completion
despite the additional of a large excess of the enol ether 2.[9]
These drawbacks of Brønsted acid promoters represent a
severe limitation from a practical point of view, and hetero-
geneous acidic catalysts have consequently been devel-
oped.[10] As a result of their superior activity, Lewis acids
have been advantageously used in place of Brønsted acids
in such tetrahydropyranylations of hydroxy-containing
compounds.[11] However, when classical Lewis acids
(BF3·Et2O, SnCl4, TiCl4, ZnBr2, ...) are used, stoichiometric
amounts – or often more – of these reagents are required
in order to achieve synthetically useful results. Further-
more, these Lewis acid-mediated protections not only have
to be carried out under strictly anhydrous conditions, but
they also release large amounts of environmentally hazard-
ous wastes. To improve the potential of these Lewis acid-
promoted reactions further, the development of processes
compatible with the use of reduced amounts of the acti-
vator is highly desirable.
[a] Dipartimento Scienze Chimiche, Università di Camerino,
via S.Agostino 1, 62032 Camerino, (MC), Italy,
Fax: +39-0737-402297
E-mail: enrico.marcantoni@unicam.it
[b] Dipartimento di Chimica Organica “A. Mangini”, Università
di Bologna,
v.le Risorgimento 4, 40136 Bologna, Italy
[c] Chemistry Research Centre, Boehringer Ingelheim S.p.A.,
via Lorenzini 8, 20139 Milano, Italy
In recent years much attention has been paid to the de-
velopment of water-resistant and environmentally mild
Lewis acids, such as triflates.[12] In particular, attention has
mostly focused on rare earth triflate-catalysed organic
chemistry transformations, due to their mildness and effi-
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Solvent-Free Carbon–Oxygen Bond Formation Catalysed by CeCl3·7H2O/NaI
FULL PAPER
ride as Lewis acid, and our results are summarized in
Table 1. Comparing the results obtained, we noted that the
reaction is sluggish when carried out in acetonitrile and in
the presence of CeCl3·7H2O alone, even in stoichiometric
amounts (Table 1, Entry 1). As is well known,[14] the ad-
dition of NaI increases the efficiency, and the yield is dra-
matically improved when the reaction mixture is stirred at
a temperature of 50 °C (Table 1, Entries 2 and 3). An equi-
molar ratio of CeCl3·7H2O and NaI is found to give the
best results, whereas use of an excess of sodium iodide salt
results in lower yields (Table 1, Entry 4). Further experi-
ments also showed that the amount of CeCl3·7H2O/NaI
can be reduced without an appreciable loss of activity, the
optimum conditions being 2–5 mol-% of CeCl3·7H2O/NaI.
Finally, the reaction can be carried out in shorter times
without solvent (Table 1, Entries 7, 8, and 9). This allowed
us to adopt a very simple workup procedure for the recov-
ery of the tetrahydropyranyl ether, with the reaction mix-
ture being treated with an organic solvent (Et2O) capable
of dissolving the organic material but not the catalyst,
which could then easily be removed by filtration. Because
of the broad range of applications of the CeCl3·7H2O/NaI
system as catalyst in many organic transformations and the
Scheme 1. A general method of tetrahydropyranylation of hydroxy
compounds.
ciency.[13] All these salts are commercially available but
rather expensive, and their use may not be economical, es-
pecially for large-scale synthetic operations. For this reason
we considered using the cheap and readily available rare
earth salt cerium trichloride heptahydrate, the activity of
which increases dramatically in the presence of an iodide
source.[14] Recent studies by us and by others have resulted
in the development of various chemical transformations
promoted by the CeCl3·7H2O/NaI Lewis acid combination
in organic synthesis.[15] After reactions and methodologies
involving the CeCl3·7H2O/NaI system to facilitate the
cleavage of carbon–oxygen and silicon–oxygen bonds under
neutral conditions, we also developed new methods for car-
bon–carbon[16] and nitrogen–carbon[17] bond-forming reac-
tions promoted by the CeCl3·7H2O/NaI system. On the
other hand, only two procedures in which the CeCl3·7H2O/
NaI system promotes formation of a carbon–oxygen bond
have been reported, to the best of our knowledge.[18] Thus,
as a part of our ongoing research program to develop new
methodologies involving cerium() salts, we investigated
one of the most important carbon–oxygen bond-forming
reactions in organic chemistry: the protection of hydroxy
groups. In this paper we wish to report an efficient and
versatile procedure for the conversion of alcohols and phe-
nols into the corresponding THP ethers in the presence of
catalytic amounts of the CeCl3·7H2O/NaI system under
solvent-free conditions.
Table 1. Reaction between 1-octanol (1a) and 3,4-dihydro-2H-py-
ran (2) under different experimental conditions.[a]
Entry Catalyst
Solvent Time
[h]
Temp. Yields
[°C]
[%]
1
2
CeCl3·7H2O
CH3CN 96
25
35
(1 equiv.)
CeCl3·7H2O
(1 equiv.)/
CH3CN 48
25
50
50
25
50
25
25
25
48
95
82
65
90
98
97
98
Results and Discussion
NaI (1 equiv.)
CeCl3·7H2O
(1 equiv.)/
NaI (1 equiv.)
CeCl3·7H2O
(1 equiv.)/
NaI (1.8 equiv.)
CeCl3·7H2O
(1.8 equiv.)/
NaI (1.8 equiv.)/SiO2
CeCl3·7H2O
(0.1 equiv.)/
NaI (0.1 equiv.)
CeCl3·7H2O
(0.1 equiv.)/
NaI (0.1 equiv.)
CeCl3·7H2O
(0.05 equiv.)/
NaI (0.05 equiv.)
CeCl3·7H2O
(0.02 equiv.)/
NaI (0.02 equiv.)
3
4
5
6
7
8
9
CH3CN 20
CH3CN 25
The procedure based on the Lewis acid catalytic activity
of the CeCl3·7H2O/NaI system represents an environmen-
tally benign alternative to current chemical processes that
use water-intolerant Lewis acids. The key to waste minimi-
zation in fine chemical synthesis lies in the widespread sub-
stitution of classical organic reactions employing stoichio-
metric amounts of reagents with cleaner and catalytic alter-
natives.[19] Furthermore, although performing organic reac-
tions in an aqueous medium is a current challenge set to
attract considerable attention in the coming years,[20] from
the point of view of green chemistry it would be even more
convenient to avoid the use of any solvent at all.[21] Given
that the solvent-free approach finds useful applications
when one reagent is a liquid and available in large quanti-
ties,[22] we believe that our CeCl3·7H2O/NaI-catalysed
tetrahydropyranylation of hydroxy compounds under sol-
vent-free conditions could be particularly appealing.
no sol- 20
vent
CH3CN 15
no sol- 6.5
vent
no sol-
vent
6
no sol-
vent
6
Our initial efforts focused on achieving the optimum con-
ditions for tetrahydropyranylation of 1-octanol (1a) as a
[a] All reactions were carried out by stirring mixtures of 1a
(10 mmol), DHP (13 mmol) and catalyst for the selected reaction
model hydroxy compound in the presence of cerium trichlo- times. Yields of products were estimated by GC/MS.
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Table 2. Tetrahydropyranylation of hydroxy compunds 1a–q with DHP (2) in the presence of 2–5 mol-% of CeCl3·7H2O/NaI system
under solvent-free conditions.
[a] All products were identified by their IR, NMR, and GC/MS spectra. [b] All yields refer to pure isolated compounds. [c] As a mixture
of two epimers in about 1:1 ratio in all cases. [d] Only starting material was recovered.
high efficiencies obtained, several efforts have been devoted allylic and benzylic alcohols give the corresponding tetra-
to the recovery and recycling of the catalyst.[16d,16e] We thus hydropyranyl ether adducts in excellent yields (Table 2, En-
repeated our procedure for the tetrahydropyranylation of tries 3, 4, 11, 12, and 13). Interestingly, in the case of race-
1a with DHP (2) five times without noting any appreciable mic perillyl alcohol (1d) the exocyclic double bond is not
decrease in activity.
attacked and the exo-endo isomerization phenomenon does
Application of our method to the preparation of THP- not occur (Table 2, Entry 4). Analogously, no (Z)/(E) isom-
ethers from different alcohols and phenols was investigated. erization of the double bond in 1f has been observed
The scope and efficiency of the procedure are summarized (Table 2, Entry 6).[23] Furthermore, alcohols bearing the hy-
in Table 2, and in all cases the yields of these ethers are droxy group bonded to a carbon stereogenic centre
satisfactory and comparable to those observed with dif- (Table 2, Entries 8, 15, and 16) can be protected, giving ad-
ferent heterogeneous Lewis acid catalysts. However, our ducts with complete retention of configuration.[24] Particu-
CeCl3·7H2O/NaI system has the advantages of being effec- larly interestingly, the CeCl3·7H2O/NaI system does not
tive at room temperature and avoiding the use of solvents.
cause dehydration[25] during the conversion of β-hydroxy
It can thus be observed that primary and secondary carbonyl compound 1p into the corresponding THP-ether
alcohols are smoothly transformed into the corresponding 3p under our conditions. In these hydroxy compound sub-
THP-ethers and that the reaction proceeds with excellent strates (1h, 1o, and 1p), which include a stereogenic centre,
yields under solvent-free conditions, even in cases involving the tetrahydropyranylation generates adducts with a new
sterically hindered alcohols (Table 2, Entries 7 and 8). Even stereogenic centre, however low diastereoselectivity is ob-
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Solvent-Free Carbon–Oxygen Bond Formation Catalysed by CeCl3·7H2O/NaI
FULL PAPER
served (Table 2, Entries 8, 15, and 16), and the correspond- tained in the presence of N-tert-butoxycarbonyl and acetate
ing THP-ethers are isolated as diastereomeric mixtures in groups (Table 3, Entries 1 and 2), but also that hydroxy
about 1:1 ratio. We have also observed that our tetrahydro- groups can be selectively protected in the presence of p-
pyranylation procedure is compatible with the presence of methoxybenzyl[29] and trialkylsilyl ethers,[30] which have
several functionalities such as ester (1o and 1p) and bromo been recently reported to be cleaved by stoichiometric
(1n) groups. In the latter case no halogen exchange reac- amounts of the CeCl3·7H2O/NaI system. Finally, our pro-
tion[26] occurred under these conditions. Unfortunately, the cedure is mild enough to be useful for substrates containing
reaction with tertiary alcohols shows the typical issue asso- acid-sensitive protecting groups such as 1,3-dioxolanes[31]
ciated with highly hindered substrates,[27] and only starting (Table 3, Entry 6).
material was recovered without any trace of dehydration
product (Table 2, Entry 17).
These results have established that the ability of the
CeCl3·7H2O/NaI system to mediate organic reactions
Our CeCl3·7H2O/NaI-catalysed tetrahydropyranylation either catalytically or stoichiometrically constitutes one of
was successfully applied to a variety of alcohol and phenol the most powerful strategies to achieve both selectivity and
derivatives (Table 2, Entries 11 and 12), providing fairly efficiency in synthetic chemistry. Unfortunately, the mecha-
good yields of the corresponding THP-ethers. We also in- nism of this effective catalyst for tetrahydropyranylation of
vestigated the role of electron density on the phenol moiety alcohols and phenols is not clear. Undoubtedly the presence
in the protection reaction: no apparent difference in reactiv- of NaI is essential too for this reaction, and no THP-ether
ity was detected in the presence of electron-donating sub- formation took place in absence of iodide. We believe that
stituents on the aromatic moiety, whereas the presence of the acceleration effect caused by addition of inorganic
an electron-withdrawing group on the aromatic ring re- iodide cannot be rationalized simply in terms of a halogen
tarded the protection of the hydroxy group, while no reac- exchange reaction because we have observed that CeI3
tion occurred between p-nitrophenol and 3,4-dihydro-2H- alone shows activity significantly lower than that of the
pyran.[28]
Given these results, and to evaluate the efficiency of the thus appears to be intriguing and complex, and the exact
tetrahydropyranylation procedure further, series of nature of the reactive species obtained on treatment of the
alcohols was protected in the presence of other protective substrates with the CeCl3·7H2O/NaI system is not known.
groups. The results are summarized in Table 3. It is impor- Even though it is premature to speculate on the exact
CeCl3·7H2O/NaI system.[32] The mechanistic role of NaI
a
tant to note not only that a tetrahydropyranyl ether is ob- mechanism, we have obtained some evidence that our car-
Table 3. Compatibility of the tetrahydropyranylation with other protecting groups of amines and alcohols.
[a] All products were identified by their IR, NMR, and GC/MS spectra. [b] Isolated yields.
Eur. J. Org. Chem. 2006, 1476–1482
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Experimental Section[38]
bon–oxygen bond formation is promoted by the solid
CeCl3·7H2O/NaI system. Having established, in fact, what
appeared to be the optimal conditions, we switched our at-
tention to the water of crystallization in the cerium() salt.
The water (from CeCl3·7H2O) is an important component
of the reaction system, and when anhydrous cerium()
chloride salt[33] has been employed the THP-ether products
General Remarks: 1H NMR spectra were recorded in CDCl3 at
200 MHz on a Varian Gemini 200 spectrometer and are reported
as follows: chemical shift, δ (ppm) [multiplicity, number of protons,
and coupling constant J (Hz)]. Residual protic solvent CHCl3 (δH
= 7.26 ppm) was used as the internal reference. 13C NMR spectra
were recorded in CDCl3 at 50 MHz on Varian Gemini 200 spec-
are not observed. It is also worth noting that, in contrast trometer, with use of the central resonance of CDCl3 (δC
=
to the results proposed by Patel et al.,[34] the tetrahydropy-
ranylation is not catalysed by water alone: no trace of THP-
ether has been observed on simple addition of water to the
mixture of hydroxy compound 1 and dihydropyran 2. These
experimental findings indicate that our CeCl3·7H2O/NaI
system functions as a water-tolerant oxophilic Lewis acid
catalyst under solvent-free conditions. However, according
to a paper published by Spencer,[35] investigations aimed at
confirming the effective catalyst do not preclude the exis-
77.0 ppm) as the internal reference. Infrared spectra were recorded
on a Perkin–Elmer FTIR Paragon 500 spectrometer as thin films
on NaCl plates. Only the characteristic peaks are quoted. Mass
spectra were recorded on a Hewlett–Packard 5988 gas chromato-
graph with a mass-selective detector (MSD HP 5790 MS), utilizing
electron ionization (EI) at an ionizing energy of 70 eV. A fused
silica column (30 m×0.25 mm HP-5; cross-linked 5% Ph-Me silox-
ane, 0.10 µm film thickness) was used with a helium carrier flow of
30 mLmin–1. The temperature of the column was varied, after a
delay of 3 min from the injection, from 65 °C to 300 °C with a slope
tence of a Brønsted acid-catalysed pathway in our pro- of 15 °Cmin–1.
cedure. In fact, the presence of the weak base 2,6-di-tert-
Most solvents and reagents were used without purification unless
mentioned otherwise. Solvents (EtOAc and hexanes) for flash
butyl-4-methylpyridine, which only binds to protons and is
unable to coordinate to metal cerium, due to the bulky tert-
chromatography were distilled. Cerium() chloride heptahydrate,
butyl groups,[36] significantly retards the tetrahydropyranyl- sodium iodide and 3,4-dihydro-2H-pyran are commercially avail-
able and were used without further purification. Solutions were
evaporated under reduced pressure with a rotary evaporator and
the residue was chromatographed on a Baker silica gel (230–
400 mesh) column with 30% ethyl acetate in hexane as the eluent.
Analytical thin layer chromatography was performed with pre-
coated glass-backed plates (Merck Kieselgel 60 F254) and visual-
ized with UV light (254 nm) and/or by dipping the plates into Von’s
reagent (1.0 g of ceric sulfate and 24.0 g of ammonium molybdate
in 31 mL of sulfuric acid and 470 mL of water).
ation under our conditions. THP-ethers are thus produced
catalytically in our procedure, but the real active species
have not been recognized, and the characterization of all
these species is being studied in our laboratories.
Conclusions
In conclusion, in the course of our studies in developing
new methods for transformations of organic functional
groups containing oxygen, we have established an efficient
and inexpensive method for introducing the tetrahydropy-
ranyl protecting group by use of the CeCl3·7H2O/NaI sys-
The hydroxy compounds used as starting materials were obtained
from commercial sources or (1t and 1u) were synthesized by re-
ported methods in the literature.[39] All the obtained tetrahydropy-
1
ranyl ethers were characterized by H and 13C NMR spectroscopy
and mass spectrometry, while the compounds 3a,[10d] 3b,[7] 3c,[40]
tem as a water-tolerant and heterogeneous catalyst. While 3e,[7] 3f,[7] 3g,[10d] 3h,[12] 3i,[10d] 3j,[10b], 3k,[10d] 3l,[10d] 3m,[41] 3n,[42]
3o,[43] 3p,[43] 3q,[44] 3r,[45] 3s,[11d] 3v,[28] and 3z[12] are all known, and
the treatment of tetrahydropyranyl ethers with CeCl3·7H2O
their structures are consistent with their published physical data.
in methanol provides a method for detetrahydropyranyl-
ation,[37] our CeCl3·7H2O/NaI combination represents an
General Procedure for the Tetrahydropyranylation (compounds 3a–
useful system for catalyzing the preparation of THP-ethers z): The hydroxy compound (1a–z, 1.0 mmol), 3,4-dihydro-2H-py-
ran (1.1 mmol), CeCl3·7H2O (2–5 mol-%) and NaI (2–5 mol-%)
were placed successively in a flask. After having been stirred at
room temperature for the time needed, the reaction mixture was
treated whilst stirring with Et2O (20 mL), and the catalyst mixture
was removed by filtration. The filtered extracts were concentrated
under reduced pressure, and the crude product was then purified
by silica gel chromatography (hexanes/EtOAc).
under solvent-free conditions. In addition, the simplicity of
our approach, the low cost of reagents and the fact that no
precautions to exclude moisture or oxygen from the reac-
tion system need to be taken suggest to us that the
CeCl3·7H2O/NaI combination could find applicability in
further organic transformations. In fact, after wide scien-
tific work regarding the use of the CeCl3·7H2O/NaI system
as a promoter in the cleavage of carbon–oxygen bonds, to
which different groups including ourselves have made sub-
stantial contributions, we are now describing in this paper
a new method for carbon–oxygen bond formation catalysed
by the same CeCl3·7H2O/NaI system. As in Rosini’s pro-
cedure,[18a] the catalyst functions as a promoter of forma-
2-[(4-Isopropenylcyclohex-1-enyl)methoxy]tetrahydro-2H-pyran (3d):
1H NMR: δ = 1.40–2.30 (m, 16 H, CH2 and CH3), 3.45–3.55 (m,
2 H, CH2O), 3.80–3.95 (m, 2 H, CH2), 4.55–4.65 (m, 1 H, CH),
4.73 (s, 2 H, CH2), 5.74 (s, 1 H, =CH) ppm. 13C NMR: δ = 19.7,
20.9, 25.7, 26.3, 26.9, 28.0, 30.2, 42.4, 61.8, 71.0, 96.5, 108.1, 126.4,
131.8, 149.9 ppm. IR (neat): ν = 3086, 1661, 1355 cm–1. MS: m/z =
˜
236 [M]+, 182, 155, 115, 101, 85 (100), 69, 57, 45, 41. C15H24O2
tion of the carbon–oxygen bond when the substrates pos- (236.35): calcd. C 76.23, H 10.24; found C 76.19, H 10.21.
sess a carbon–carbon double bond.
tert-Butyldimethyl[4-(tetrahydro-2H-pyran-2-yloxy)butoxy]silane
1
The applicability of the CeCl3·7H2O/NaI to other syn-
thetic problems is currently under study and will constitute
the subject of future reports.
(3t): H NMR: δ = 0.76 (s, 6 H, 2×CH3), 0.93 (s, 9 H, 3×CH3),
1.45–1.90 (m, 10 H, 5×CH2), 3.30–3.45 (m, 1 H, CH2), 3.45–3.55
(m, 1 H, CH2), 3.60–3.70 (m, 2 H, CH2), 3.70–3.80 (m, 1 H, CH2),
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Solvent-Free Carbon–Oxygen Bond Formation Catalysed by CeCl3·7H2O/NaI
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3.85–3.95 (m, 1 H, CH2), 4.50–4.60 (m, 1 H, CH) ppm. 13C NMR:
δ = –5.2, 18.3, 19.6, 25.5, 25.9, 26.1, 29.6, 30.7, 62.2, 63.0, 67.4,
7891–7894; d) J. S. Yadav, B. V. Subba Reddy, D. Guaneshwar,
New J. Chem. 2003, 27, 202–204; e) V. V. Namboodiri, R. S.
Verma, Chem. Commun. 2002, 342–343; f) N. Deka, J. C.
Sarma, Synth. Commun. 2000, 30, 4435–4441; g) M. A. Reddy,
L. R. Reddy, N. Bhanumathi, K. R. Rao, Synth. Commun.
2000, 30, 4323–4328; h) N. Rezai, F. A. Meybodi, P. Salehi,
Synth. Commun. 2000, 30, 1799–1805; i) G. Maity, S. C. Roy,
Synth. Commun. 1993, 23, 1667–1671.
98.7 ppm. IR (neat): ν = 2942, 2878, 1431, 1280, 1050 cm–1. MS:
˜
m/z = 330 [M]+, 315, 273, 173, 143, 101, 85 (100), 69, 57, 43.
C15H32O3Si (288.50): calcd. C 62.45, H 11.18; found C 62.39, H
11.10.
Triisopropyl[4-(tetrahydro-2H-pyran-2-yloxy)butoxy]silane (3u): 1H
NMR: δ = 0.95–1.15 (m, 21 H, CH and CH3), 1.45–1.85 (m, 10 H,
5×CH2), 3.35–3.45 (m, 1 H, CH2), 3.45–3.55 (m, 1 H, CH2), 3.65–
3.80 (m, 3 H, CH and CH2), 3.82–3.90 (m, 1 H, CH2), 4.56–4.60
(m, 1 H, CH) ppm. 13C NMR: δ = 12.0, 18.0, 20.0, 25.5, 26.0, 29.5,
[12] J. R. Stephens, P. L. Butler, C. H. Claw, M. C. Oswald, R. C.
Smith, R. S. Mohan, Eur. J. Org. Chem. 2003, 3827–3831.
[13] Kobayashi, S., in: Lanthanides: Chemistry and Use in Organic
Synthesis (Ed.: S. Kobayashi), Springer: Berlin, 1999; p. 63–
118.
31.0, 62.0, 63.5, 67.5, 99.3 ppm. IR (neat): ν = 2945, 2893, 1420,
˜
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Acknowledgments
Work was carried out in the framework of the National Project
“Stereoselezione in Sintesi Organica. Metodologie e Applicazioni”
and the National Project “Studio degli Aspetti Teorici ed Applica-
tivi degli Aggregati di Molecole Target su Siti Catalitici Stereoselet-
tivi” supported by the MIUR, Rome, by the University of Bologna
and by the University of Camerino. M. P. gratefully acknowledges
the Pfizer Ascoli Piceno Plant for a postgraduate fellowship.
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G. Bartoli, E. Marcantoni et al.
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Eur. J. Org. Chem. 2006, 1476–1482