Preparation, Characterization, and Synthetic Uses of Lanthanide(III) Catalysts Supported on Ion Exchange Resins

Article abstract of DOI:10.1021/jo961933+

Lanthanide(III) catalysts supported on ion exchange resins (Ln-resins) were prepared from Dowex, Amberlite, Amberlyst, and other cation exchange resins. The amount of lanthanides on resin supports was measured through EDTA titration. The results indicated that the lanthanides in aqueous solution exchanged with almost all the cations (H⁺ or Na⁺) on the resins to form stable ionic complexes between the lanthanides(III) and the resins. The effects of resin types, resin sizes, and lanthanide salts were investigated with a reaction of indole and hexanal in aqueous solution and with an aldol reaction of benzaldehyde and silyl enol ether in organic solvents. The study found that among ion exchange resins tested Amberlyst XN-1010 and Amberlyst 15 complexed with lanthanides(III) were the most effective catalysts. In addition, the selective Ln-resins were utilized to catalyze acetalization of aldehydes, aldol reaction of formaldehyde or benzaldehyde in aqueous solution, nucleophilic addition to an imine, allylation of an aldehyde, an aza Diels-Alder (DA) reaction, and a ring-opening reaction of an epoxide. Furthermore, glycosylation of alcohol using glucosyl fluoride as a donor was also promoted with the Ln-resin. Thus, this work demonstrated potential uses of lanthanide(III) catalysts supported on ion exchange resins in routine organic reactions.

Full text of DOI:10.1021/jo961933+

J . Org. Chem. 1997, 62, 3575-3581
3575
P r ep a r a tion , Ch a r a cter iza tion , a n d Syn th etic Uses of
La n th a n id e(III) Ca ta lysts Su p p or ted on Ion Exch a n ge Resin s
Libing Yu, Depu Chen, J un Li, and Peng George Wang*
Department of Chemistry, University of Miami, P.O. Box 249118, Coral Gables, Florida 33124
Received October 15, 1996X
Lanthanide(III) catalysts supported on ion exchange resins (Ln-resins) were prepared from Dowex,
Amberlite, Amberlyst, and other cation exchange resins. The amount of lanthanides on resin
supports was measured through EDTA titration. The results indicated that the lanthanides in
aqueous solution exchanged with almost all the cations (H+ or Na+) on the resins to form stable
ionic complexes between the lanthanides(III) and the resins. The effects of resin types, resin sizes,
and lanthanide salts were investigated with a reaction of indole and hexanal in aqueous solution
and with an aldol reaction of benzaldehyde and silyl enol ether in organic solvents. The study
found that among ion exchange resins tested Amberlyst XN-1010 and Amberlyst 15 complexed
with lanthanides(III) were the most effective catalysts. In addition, the selective Ln-resins were
utilized to catalyze acetalization of aldehydes, aldol reaction of formaldehyde or benzaldehyde in
aqueous solution, nucleophilic addition to an imine, allylation of an aldehyde, an aza Diels-Alder
(DA) reaction, and a ring-opening reaction of an epoxide. Furthermore, glycosylation of alcohol
using glucosyl fluoride as a donor was also promoted with the Ln-resin. Thus, this work
demonstrated potential uses of lanthanide(III) catalysts supported on ion exchange resins in routine
organic reactions.
In tr od u ction
and related processes on a large scale. Polymeric organic
supports are dominated by functionalized cross-linked
polystyrene in various forms.8 The supported species
include common chemical catalysts and biocatalysts such
as immobilized enzymes. Under the increasing pressure
of environmental problems caused by the chemical in-
dustry, solid phase catalysis is recognized to play a
leading part in the development of green chemistry. The
main advantages to exploit solid phase catalysts in
organic synthesis are to adjust reactivity, improve selec-
tivity, simplify separation, recycle the catalysts, and
eventually reduce hazardous pollution to achieve envi-
ronmentally friendly processes.
Lanthanides have been extensively used in organic
synthesis because lanthanide-mediated reactions display
high chemical and stereoselectivities.9 Tetravalent lan-
thanides such as cerium(IV) are effective and mild one-
electron oxidants of alcohols and electron-rich aromatic
compounds.10 Cerium(IV) was complexed to Nafion 511
to make a solid oxidation catalyst for transformation of
a secondary alcohol to a ketone with NaBrO3 as co-
oxidant.11 Trivalent lanthanides can serve as hard Lewis
acids to promote reactions of carbonyl compounds.9b For
example, Ce(III)-mediated selective 1, 2-addition of NaBH4
Organic synthesis supported by inorganic or organic
solid phases has been playing an important role in
chemistry and biology. During the last 3 decades, the
introduction of solid phase technology has made synthesis
of complicated peptides1 and nucleotides2 possible. Ap-
plications of solid phases include three aspects: (a) solid-
supported substrates, (b) supported reagents, (c) solid
catalysts. As the interest in combinatorial chemistry3
increases, a lot of efforts are currently being made to
execute various organic reactions with the substrates on
solid phases in order to build up a library of small
molecules.4 Development of reagents supported on solid
phases has blossomed since the use of silver carbonate
on Celite was reported by Fetizon and Golfier.5 There
are numerous potential advantages for immobilized
reagents, but the most important are significant improve-
ment in reactivity and selectivity and simplified operation
and isolation.6 Solid catalysts have been used routinely
in chemical laboratories and industrial processes. Inor-
ganic solid acids are widely utilized in petroleum industry
as cheap and effective catalysts.7 For example, clays and
zeolites have been used to bring about catalytic cracking
X Abstract published in Advance ACS Abstracts, May 15, 1997.
(1) (a) Merrifield, R. B. Angew. Chem., Int. Ed. Engl. 1985, 24, 799.
(b) Barany, G.; Kneib-Cordonier, N.; Mullen, D. G. Int. J . Pept. Protein
Res. 1987, 30, 705. (c) Kent, S. B. H. Annu. Rev. Biochem. 1988, 57,
957.
(2) (a) Letsinger, R. L.; Mahadevan, V. J . Am. Chem. Soc. 1965, 87,
3526. (b) Sproat, B. S.; Gait, M. J . Oligonucleotide Synthesis: a Pratical
Approach; IRL Press: Oxford, 1984; p 83. (b) Atkinson, T.; Smith, M.
In Oligonucleotide Synthesis: a Practical Approach; Gait, M. J ., Ed.;
IRL Press: Oxford, 1984; p 35. (c) Froehler, B. C.; Ng, P. G.; Matteucci,
M. D. Nucleic Acids Res. 1986, 14, 5399. (d) Blackburn, G. M., Gait,
M. J ., Eds. Nucleic Acids in Chemistry and Biology; IRL Press: Oxford,
1990.
(3) (a) Thompson, L. A.; Ellman, J . A. Chem. Rev. 1996, 96, 555. (b)
Fruchtel, J . S.; J ung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17.
(4) (a) Strocker, A. M.; Keating, T. A.; Tempeat, P. A.; Armstrong,
R. W. Tetrahedron Lett. 1996, 37, 1149. (b) Dinh, T. Q.; Armstrong, R.
W. Tetrahedron Lett. 1996, 37, 1161.
(5) Fetizon, M.; Golfier, M. C. R. Acad. Sci. Ser. 1968, C 267, 900.
(6) Clark, J . H. Catalysis of Organic Reactions by Supported
Inorganic Reagents; VCH: New York, 1994.
(7) For a review book, see: Solid Supports and Catalysts in Organic
Synthesis; Smith, K., Ed.; Ellis Harwood PTR Prentice Hall: New York,
1992.
(8) (a) Sherrington, D. C., Hodge, P., Ed. Synthesis and Separations
Using Functional Polymers; J ohn Wiley & Sons: New York, 1988. (b)
Frechet, J . M.; Draling, G. D.; Itsuno, S.; Lu, P.-L.; Meftah, M. V.; Rolls,
W. A., J r. Pure Appl. Chem. 1988, 60, 353. (c) Laszlo, P., Ed.
Preparative Chemistry Using Supported Reagents; Academic Press:
London, 1987. (d) Ford, W. T., Ed. Polymeric Reagents and Catalysts;
ACS Symp. Ser. 308; American Chemical Society: Washington, DC,
1986. (e) Hodge, P., Sherrington, D. C., Eds. Polymer-Supported
Reactions in Organic Synthesis; J ohn Wiley & Sons: New York, 1980.
(9) For applications of lanthanides in organic synthesis, see reviews
and a book: Molander, G. Chem. Rev. 1992, 92, 29. (b) Marshman, R.
Aldrichim. Acta 1995, 28, 77. (c) Imamoto, T. Lanthanides in Organic
Synthesis; Academic Press: London, 1994.
(10) (a) Ho, T.-L. Synthesis 1973, 347. (b) Ho, T.-L. Organic Synthesis
by Oxidation with Metal Compounds; Mijs, W. J ., de J onge, C. R. H.
I., Eds.; Plenum Press: New York, 1977; p 330.
(11) Kanemoto, S.; Saimoto, H.; Oshima, K.; Nozaki, H. Tetrahedron
Lett. 1984, 25, 3317.
S0022-3263(96)01933-0 CCC: $14.00 © 1997 American Chemical Society

3576 J . Org. Chem., Vol. 62, No. 11, 1997
Ta ble 1. Yb-Resin s P r ep a r ed fr om Ytter biu m Su lfa te a n d Differ en t Resin s
Yu et al.
H+ exchange
capacity (mmol/g)
Yb content
(mmol/g)b
exchange
entry
Ln-resin
Yb-Dowex
ion exchange resin useda
percentagec (%)
1
2
Dowex 50X-8, SA, gel, 20-50 mesh
Amberlyst XN-1010, macroreticular,
high-specific surface
5.1
2.58
1.57
0.76
92
92
Yb-XN1010
3
4
5
6
7
8
9
10
11
Yb-Amberlyst 15
Yb-Amberlyst 15(w)
Yb-CG50
Yb-IRP
Yb-Nafion
Yb-IR118
Yb-IR120
Yb-Sephadex
Yb-Cellulose
Amberlyst 15, SA, macroreticular
Amberlyst 15(wet), SA, macroporous
Amberlite CG-50, WA, gel, 100-200 mesh
Amberlite IRP-64, 100-400 mesh
Nafion NR-50
Amberlite IR-118
Amberlite IR-120
SP-Sephadex SP-C25-120, 40-120 µm
sulfoxyethyl cellulose fast flow, fibrous form
4.85
4.80
9.32
9.69
0.89
4.85
4.88
2.32
2.33
1.52
1.60
0.42
0.42
0.30
1.62
1.53
0.76
0.77
94
100
14
13
100
100
94
98
99
a
b
Entries 5 and 6, carboxylic acids; others, sulfonic acids. Yb content calculated according to the formula in the text. c Exchange
percentage (EP) calculated as: EP ) 3 × Yb content/H+ exchange capacity.
Ta ble 2. Yb-Dow ex P r ep a r ed fr om Dow ex 50WX 8 (H+
for m , 20-50 m esh ) a n d Differ en t Ytter biu m (III) Sa lts
Sch em e 1. P r ep a r a tion of Ln -Resin s
Yb salt
Cl-
NO3
SO4
OTf-
-
2-
Yb capacitya (mmol/g)
1.57
92
1.67
98
1.70
100
1.70
100
exchange percentage (%)b
a
Yb content was calculated according to the formula in the text.
b
Exchange percentage (EP) calculated as: EP ) 3 × Yb content/
to unsaturated ketones has become a standard method
in organic synthesis.12 Divalent lanthanides, particularly
SmI2, are versatile reducing agents which initiate radical
reactions between a halide and unsaturated functional-
ities and have been used in the synthesis of natural
products.13 Recently, researchers have found that lan-
thanide triflates are water tolerable and recyclable Lewis
acids which catalyze a variety of important organic
reactions in mild conditions under organic or protic
solvents.9b,14
H+ exchange capacity.
resins used in our experiments, which are commercially
available in strong acid form or weak acid form. We first
measured the proton capacity of the dry resins by acid
base titration. Amberlite IRP-64 (100-400 mesh) con-
tains the highest capacity of 9.69 mmol/g. Owing to the
heavier atomic weight of fluorine, Nafion NR-50 has the
lowest capacity of 0.89 mmol/g. Dowex and Amberlyst
XN-1010 contain medium amounts of protons.
Due to the versatility of lanthanide catalysts in organic
synthesis, we envisioned that lanthanides(III) supported
on ion exchange resins would afford a novel type of solid
phase Lewis acids which take advantage of the merits of
both lanthanides(III) and the solid phase (e.g., possessing
catalytic properties of lanthanides and simplifying isola-
tion of products (Scheme 1)). In fact, ion exchange resins
have been exploited to separate rare earth metals.
Relative binding strength (or affinity) among metal ions
of different groups as well as varied charges have been
measured.15 For example, lanthanide(III) cations bind
approximately 50-60 times more strongly than Li+ to
cation exchange resins. Reccently, Kobayashi16 reported
Sc(III) catalysts supported on solid phase. Herein we
report our work on the use of lanthanide catalysts
supported on organic polymers (Ln-resins).
Considering the similar properties of the trivalent
lanthanides(III), ytterbium(III) was chosen to study the
effect of different ytterbium salts in the exchange process.
Ytterbium(III) nitrate, chloride, sulfate, or triflate was
exchanged with Dowex 50WX-8 (H+ form). The exchange
percentage on the resins was from 92% to 100% (Table
2). Long exchange times and higher concentrations of
ytterbium salts helped complete the exchange. In terms
of efficiency and cost, lanthanide sulfates are suitable
sources of lanthanides for the preparation of Ln-resins.
The above data showed that more than 90% of the
protons on the resins could be exchanged with lan-
thanides. In order to exclude possible influences of the
unexchanged protons on Yb-resins in the reactions we
planned to perform, the resins (H+ form) were first
transformed into the Na+ form. The capacity of Yb(III)
on different Yb-resins is summarized in Table 1 along
with exchange percentage. It is noteworthy that we
employed aqueous solution of lanthanides to perform the
exchange between resins and lanthanides at room tem-
perature, while Kobayashi16a used acetonitrile under
reflux conditions to prepare Sc-Nafion. The Yb-Nafion
we prepared contained 0.30 mmol/g ytterbium(III); in
comparison, the Sc-Nafion was reported to contain 0.29
mmol/g scandium(III).16 Our method appears convenient
to prepare Ln-resins because it avoids heating and
organic solvents.
Resu lts a n d Discu ssion
P r ep a r a tion a n d Ch a r a cter iza tion of th e La n -
t h a n id es Su p p or t ed on R esin s. Table 1 lists the
(12) (a) Luche, J .-L. J . Am. Chem. Soc. 1978, 100, 2226. (b) Luche,
J .-L.; Rodriguez-Hahn, L.; Crabbe, P. J . Chem. Soc., Chem. Commun.
1978, 601. (c) Gemal, A. L.; Luche, J .-L. J . Am. Chem. Soc. 1981, 103,
545(143. ) (a) Soderquist, J . A. Aldrichim. Acta 1991, 24, 15. (b) Molander,
G. Org. React. 1994, 46, 211.
(14) (a) Yu, L.-B.; Chen, D.-P.; Wang, P. Tetrahedron Lett. 1996,
37, 2169. (b) Chen, D.-P.; Yu, L.-B.; Wang, P. Tetrahedron Lett. 1996,
37, 4467. (c) Yu, L.-B.; Chen, D.-P.; Li, J .; Wang, P.; Bott., S. J . Org.
Chem. 1997, 62, 208. (d) Yu, L.-B.; Li, J .; Ramirez, J .; Chen, D.-P.;
Wang, P. G. J . Org. Chem. 1997, 62, 907.
(15) (a) Strelow, F. W. E.; Rethemeyer, R.; Bothma, C. J . C. Anal.
Chem. 1965, 37, 106. (b) Strelow, F. W. E.; Van Zyl, C. R.; Bothma, C.
J . C. Anal. Chim. Acta 1969, 45, 81.
(16) (a) Kabashayi, S.; Nagayama, S. J . Org. Chem. 1996, 61, 2256.
(b) Kobayashi, S.; Nagayama, S. J . Am. Chem. Soc. 1996, 118, 8977.
In order to test the effect of different rare earth metals
in the catalysis, we prepared Ln-resins (La, Pr, Nd, Gd,
Dy, Er, Yb, and Sc) by the exchange of Amberlyst XN-
1010 with lanthanide salts following the above method
(Table 3). The content of lanthanides on these resins was
around 0.75 mmol/g.

Ln(III) Catalysts Supported on Ion Exchange Resins
J . Org. Chem., Vol. 62, No. 11, 1997 3577
Ta ble 3. Ln -Resin s P r ep a r ed fr om Differ en t La n th a n id es
Ta ble 4. Yield s of Rea ction s 1 a n d 2 Ca ta lyzed by
Yb-Resin sa
content of Ln(III) on
entry
Ln-resin
Ln used
resin (mmol/g)a
yields (%)
1
2
3
4
5
6
7
8
La-XN1010
Pr-XN1010
Nd-XN1010
Gd-XN1010
Dy-XN1010
Er-XN1010
Yb-XN1010
Sc-XN1010
LaCl3
0.72
0.78
0.75
0.70
0.74
0.77
0.79
0.74
entry
Yb-resin
reaction 1
reaction 2
Pr(OTf)3
Nd(OTf)3
Gd(OTf)3
Dy(OTf)3
Er(OTf)3
YbCl3
1
2
3
4
5
6
7
8
9
Yb-Dowex-1
Yb-Dowex-2
Yb-XN1010
Yb-15
Yb-15(w)
Yb-CG50
Yb-IRP64
Yb-Nafion
Yb-IR118
Yb-IR120
Yb-Sephadex
Yb-Cellulose
76
84
93
90
89
18
20
30
34
16
15
10
51
47
83
89
86
7
Sc(OTf)3
9
a
30
49
46
33
42
Yb content was calculated according to the formula in the text.
10
11
12
Sch em e 2. Rea ction of In d ole w ith Hexa n a l
Ca ta lyzed by Yb(III)-Resin s
a
Reactions 1 and 2 are illustrated in Schemes 2 and 3,
respectively.
Ta ble 5. Resu lts of Rea ction s 1 a n d 2 Ca ta lyzed by
Differ en t La n th a n id es over Am ber lyst XN-1010a
yields (%)
Syn th etic Ap p lica tion s of Ln -Resin s. To evaluate
how efficiently the lanthanides supported on ion ex-
change resins work as solid Lewis acid catalysts in
organic synthesis, we studied two reactions with respect
to yields, solvents, and recyclability: (i) a reaction of
indole with hexanal and (ii) an aldol reaction of benzal-
dehyde with a silyl enol ether. Based on the results of
these two reactions, we chose an optimal Ln-resin to
catalyze a variety of other reactions.
entry
Ln-XN1010
reaction 1a
reaction 2a
1
2
3
4
5
6
7
8
Sc
La
Pr
Nd
Gd
Dy
Er
92
91
89
91
92
92
88
92
85
71
75
73
72
78
81
83
Yb
a
(i) Rea ction of In d ole w ith Hexa n a l. Reactions17
of indoles with aldehydes or ketones to give 2 + 1
coupling products are well known and have been cata-
lyzed by protic acids18 or Lewis acids19 such as BF3‚OEt2.
We recently found that the reactions of indoles with
aldehydes or ketones can be catalyzed in an ethanol/
water system by lanthanide triflates.14b Here we used
several different Yb-resins to catalyze the reaction of
indole with hexanal in an ethanol/water solvent system
(Scheme 2). The results are summarized in Table 4.
Amberlyst XN-1010 and Amberlyst 15 catalyzed the
reaction most effectively. After 24 h the reaction gave
more than 90% yield of product 1. For CG-50 and IRP-
60, which are weak acids (carboxylic aicds), the yields
were around 20%. Although Yb-Sephadex and Yb-
Cellulose bear sulfonated anions, only limited catalysis
was observed. For Yb-Dowex and Yb-IR118, the reaction
took a longer time (48 h) to achieve a yield of 90%.
To compare the catalytic effect of different rare earth
ions, the reaction was run in the presence of the eight
Ln-resins (Sc, La, Pr, Nd, Gd, Er, Dy, and Yb(III)),
respectively. Similar to the results obtained with soluble
lanthanide triflate salts,14b no obvious differences were
observed for these resin-supported catalysts in terms of
the reaction yields (Table 5).
Reaction
1 and 2 are illustrated in Schemes 2 and 3,
respectively.
Ta ble 6. Effect of Resin Size on th e Rea ction of In d ole
w ith Hexa n a l
resin size
(mesh)
Yb content
(mmol/g)a
yield
(%)
entry
Ln-resin
1
2
3
4
Yb-Dowex 50X-8
Yb-Dowex 50X-8
Yb-Dowex 50X-8
Yb-Dowex 50X-2
20-50
1.57
1.44
1.57
1.43
76
84
86
30
100-200
400-200
400-200
a
Yb content was calculated according to the formula in the text.
Sch em e 3. Ald ol Rea ction Ca ta lyzed by
Yb(III)-Resin s in Dich lor om eth a n e
Yb-Dowex 50WX-8 of different sizes. The resin of smaller
size gave a better yield of product 1 (Table 6). In
addition, Yb-Dowex with a cross-linking degree of 2% was
not effective to catalyze the reaction.
(ii) Ald ol Rea ction of Ben za ld eh yd e a n d Silyl
En ol Eth er 2. Traditional Lewis acids used in aldol
reaction are moisture sensitive so that the reaction must
be done under water free conditions. Lanthanide com-
plexes can serve as Lewis acids to promote the reaction
of silyl enol ethers with aldehydes without the require-
ment of water free conditions.20 We examined the
catalytic effect of the Ln-resins on the reaction of ben-
zaldehyde and silyl enol ether 2 (Scheme 3).
The effect of particle size of the solid support was
examined by performing the reaction in the presence of
(17) (a) Remers, W. Chem. Heterocycl. Compd. 1972, 25 -(1), 1. (b)
J ones, R.; Bean, G. The Chemistry of Pyrroles; Academic Press:
London, 1977.
(18) (a) Gregorovich, B.; Liang, K.; Clugston, D.; MacDonald, S. Can.
J . Chem. 1968, 46, 3291. (b) Roomi, M.; MacDonald, S. Can. J . Chem.
1970, 48, 139.
(19) (a) Chatterjee, A.; Manna, S.; Benerji, J .; Pascard, C.; Prange,
T.; Shoolery, J . J . Chem. Soc., Perkin Trans. I 1980, 553. (b) Banerji,
J .; Chatterjee, A.; Manna, S.; Pascard, C.; Prange, T.; Shoolery, J .
Heterocycles 1981, 15, 325. (c) Roder, E. Arch. Pharm. (Weinheim, Ger.)
1972, 305, 96. (d) Roder, E. Arch. Pharm. (Weinheim, Ger.) 1972, 305,
117. (e) Noland, W.; Venkiteswaren, M.; Richards, C. J . Org. Chem.
1961, 26, 4241.
Firstly, the reaction was carried out overnight in
dichloromethane in the presence of different resin sup-
(20) (a) Vougioukas, A. E.; Kagan, H. B. Tetrahedron Lett. 1987, 28,
5513. (b) Kobayashi, S. Synthesis 1993, 371.

3578 J . Org. Chem., Vol. 62, No. 11, 1997
Yu et al.
Ta ble 7. Recycla bility of Am ber lyst XN1010-Yb(III) for
Rea ction 2a
lanthanide(III) should be accepted as a general method
of choice for acetalization of aldehydes.
run
1
2
3
4
5
6
7
8
9
10
Ald ol Rea ction s in Aqu eou s Solu tion . The Mu-
kaiyama reaction24 of a silyl enol ether with aldehydes
or ketones requires a catalyst such as TiCl4 under strictly
nonaqueous conditions. Kobayashi first reported the use
of lanthanide(III) triflate as catalyst for the Mukaiyama
reaction using a commercially available aqueous form-
aldehyde solution to make hydroxymethyl adducts.25 We
tested the Ln-resins in the reaction of (cyclohexenyloxy)-
trimethylsilane with formaldehyde in aqueous THF
(Table 8, entry 3). Yb-XN1010 and Yb-Amberlyst 15
displayed better catalytic effects than Yb-Nafion. How-
ever, only Yb-Nafion catalyzed the reaction of benzalde-
hyde with (cyclohexenyloxy)trimethylsilane to give prod-
ucts 8 and 9 (Table 8, entry 4).
Rea ction of a n Im in e w ith Silyl En ol Eth er 2.
Lanthanide triflates were reported to catalyze the reac-
tion of an imine and a silyl enol ether.26 In our hands,
Yb-XN1010 was found to catalyze the reaction of silyl
enol ether 2 and an imine prepared by condensation of
benzaldehyde and aniline (Table 8, entry 5).
Allyla tion of Hexa n a l w ith Tetr a a llyltin . Lan-
thanides were reported to catalyze the reaction of car-
bonyl compounds with tetraallyltin in an aqueous
medium.16a,27 Here Yb-XN1010 was also found to cata-
lyze the reaction of hexanal and tetraallytin in a toluene/
ethanol/H2O solvent system (Table 8, entry 6). In this
case, Yb-XN1010 was actually better than Yb-Nafion.
Aza Diels-Ald er Rea ction of Hexa n a l, Ben zy-
la m in e Hyd r och lor id e, a n d Cyclop en ta d ien e. We
recently reported that lanthanide(III) triflate can serve
as an effective catalyst for aza DA reactions28,29 in
aqueous solution between inactivated iminium salts
generated in situ from aldehydes and amine hydrochlo-
rides under Mannich-like conditions with dienes. The
reaction yields were improved significantly with the use
of lanthanides, and many previously unreactive alde-
hydes could be used in the aza DA reaction.14a Therefore,
Yb-Amberlyst 15 was implemented into the reaction of
hexanal, benzylamine hydrochloride, and cyclopentadi-
ene. We found that the resin increased reaction yield
from 7% to 22%, but it was not so effective as ytterbium
triflate in solution (Table 8, entry 7).
yield (%) 83 76 73 79 80 71 79 78 80 79
a
Reaction 2 is illustrated in Scheme 3.
ports with ytterbium as the lanthanide ion. Mixtures of
silylated and unsilylated aldols 3 and 4 were formed, and
3 was desilylated to 4 when the filtrate was treated with
TFA in dichloromethane. The reaction yields listed in
Table 4 indicate that the supports have an important
impact on the reaction. Weak acid resins exhibited very
poor catalytic effects. Strong sulfonated resins exhibited
moderate to excellent catalysis. Moreover, the surface
area and pore size of the resin were crucial to the
performance of catalysis. Amberlyst XN-1010 and Am-
berlyst 15, which were designed to have large surface
areas, were found to be the best catalysts in this aldol
reaction. Dowex resins, on the other hand, gave moder-
ate yields. Sephadex and cellulose did not display
satisfactory results.
Secondly, the reaction was carried out in the presence
of different lanthanides(III) (Sc, La, Pr, Nd, Gd, Er, Dy,
and Yb(III)) on Amberlyst XN-1010. The reaction yields
were comparable (Table 5). Thirdly, we used the Yb-
XN1010 catalyst 10 successive times for the aldol reaction
and did not find any loss of catalytic activity (Table 7).
Thus, ion exchange-supported lanthanide(III) catalysts
can be recycled and reused.
Oth er Rea ction s Ca ta lyzed by Ln -Resin s. The
above results showed that Amberlyst XN-1010 and
Amberlyst 15, which have high cross-linking degrees and
large surface areas, are suitable supports for lanthanide
catalysts. Thus we employed Ln-resins Yb-XN1010 or
Yb-Amberlyst 15 to catalyze the formation of acetals,
aldol reactions in aqueous solution, nucleophilic addition
to an imime, allylation of an aldehyde, aza DA reaction,
ring-opening reaction of an epoxide, and glycosylation
using glycosyl fluorides as a donor (Table 8).
Aceta liza tion . Lanthanide salts have proven to be
extraordinary catalysts for acetalization, providing es-
sentially quantitative yields of desired acetals with
minimal side effect22 (i.e., rearrangement, epimerization,
or racemization). In addition, previous examples have
demonstrated the ability of lanthanide Lewis acids to
chemoselectively acetalize aldehydes in the presence of
ketones.23 When Yb-XN1010 was used as a catalyst,
p-bromobenzaldehyde was quantitatively transformed to
an acetal in a mixture of dichloromethane and trimethyl
orthoformate (5/1) (Table 8, entry 1). In a mixture of
methanol and trimethyl orthoformate (5/1), Yb-Amberlyst
15 catalyzed acetalization of (S)-citronellal ((3S), 7-dim-
ethyl-6-octenal) (Table 8, entry 2). Obviously, this pro-
cess is a convenient operation because Ln-resin can be
filtered off and, more importantly, products are not
contaminated. Thus, the ion exchange resin-supported
R in g-Op en in g R ea ct ion of 1,2-E p oxyoct a n e in
Meth a n ol. Lanthanides are known to catalyze the ring
(24) (a) Mukaiyama, T.; Narasaka, K.; Banno, T. Chem. Lett. 1973,
1101. (b) Mukaiyama, T.; Narasaka, K.; Banno, T. J . Am. Chem. Soc.
1974, 96, 7503.
(25) (a) Kobayashi, S. Chem. Lett. 1991, 2087. (b) Kabayashi, S.;
Hachiya, I. J . Org. Chem. 1994, 3590. (c) Kobayashi, S.; Hachiya, I.
Tetrahedron Lett. 1992, 33, 1625.
(26) Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S.; Hachiya,
I. Synlett 1995, 233.
(27) (a) Hachiya, I.; Kobayashi, S. J . Org. Chem. 1993, 58, 6958. (b)
Kobayashi, S.; Nagayama, S. J . Org. Chem. 1996, 61, 2256.
(28) (a) Larsen, S. D.; Grieco, P. A. J . Am. Chem. Soc. 1985, 107,
1768-1769. (b) Grieco, P. A.; Larsen, S. D.; Fobare, W. F. Tetrahedron
Lett. 1986, 27, 1975-1978. (c) Grieco, P. A.; Parker, D. T.; Fobare, W.
F.; Ruckle, R. J . Am. Chem. Soc. 1987, 109, 5859-5861. (d) Grieco, P.
A.; Bahsas, A. J . Org. Chem. 1987, 52, 5746-5749. (e) Grieco, P. A.;
Clark, J . D. J . Org. Chem. 1990, 55, 2271-2272. (f) Grieco, P. A.;
Larsen, S. D. Org. Synth. 1990, 68, 206-209.
(21) Luche, J .-L.; Gemal, A. L. J . Chem. Soc., Chem. Commun. 1978,
976.
(22) Mori, S.; Aoyama, T.; Shioiri, T. Tetrahedron Lett. 1986, 27,
6111.
(23) (a) Taylor, M. D.; Minaskanian, G.; Winzenberg, K. N.; Santone,
P.; Smith, A. B., III. J . Org. Chem. 1982, 47, 3960. (b) Satoh, T.;
Kaneko, Y.; Okuda, T.; Uwaya, S.; Yamakawa, K. Chem. Pharm. Bull.
1984, 32, 3452. (c) Cockerill, G. S.; Kocienski, P.; Treadgold, R. J .
Chem. Soc., Perkin Trans. 1 1985, 2101. (d) Arai, Y.; Yamamoto, M.;
Koizumi, T. Bull. Chem. Soc. J pn. 1988, 61, 467. (e) Kuo, D. L.; Money,
T. Can. J . Chem. 1988, 66, 1794. (f) Brandes, E.; Grieco, P. A.; Garner,
P. J . Chem. Soc., Chem. Commun. 1988, 500. (g) Baudouy, R.; Prince,
P. Tetrahedron 1989, 45, 2067.
(29) (a) Waldmann, H. Angew. Chem., Int. Ed. Engl. 1988, 27, 274-
275. (b) Waldmann, H. Liebigs Ann. Chem. 1989, 231-238. (c) Walma,
H.; Braun, M. Liebigs Ann. Chem. 1991, 1045-1048. (d) Bailey, P. D.;
Brown, G. R.; Korber, F.; Reed, A.; Wilson, R. D. Tetrahedron:
Asymmetry 1991, 2, 1263-1282. (e) Bailey, P. D.; Wilson, R. D.; Brown,
G. R. J . Chem. Soc., Perkin Trans. I 1991, 1337-1340. (f) Stella, L.;
Abraham, H.; Feneau-Dupont, J .; Tinant, B.; Decercq, J . P. Tetrahe-
dron Lett. 1990, 31, 2603-2606. (g) Abraham, H.; Stella, L. Tetrahe-
dron 1992, 48, 9707-9718.

Ln(III) Catalysts Supported on Ion Exchange Resins
J . Org. Chem., Vol. 62, No. 11, 1997 3579
Ta ble 8. Ln -Resin -Ca ta lyzed Rea ction s
opening of oxiranes with many nucleophiles such as
amine30 and cyanide.31 Here the use of resin-supported
lanthanide(III) was demonstrated in the ring-opening
reaction of 1, 2-epoxyoctane to result in two isomers (1.7/
1) in methanol in the presence of Yb-Amberlyst 15 (Table
8, entry 8) with an excellent yield.
Lanthanide triflates can also promote this reaction, but
removal of the soluble lanthanide is troublesome.
Con clu sion
Lanthanides(III) supported on ion exchange resin are
a novel type of solid acid catalyst that combine the Lewis
acid properties of the lanthanide and the advantages of
solid phase. The preparation of the resin-supported
catalysts is straightforward, and the resultant catalysts
are stable and active under common conditions (acidic
conditions and room temperature) in organic synthesis.
The catalysts have been demonstrated to be effective in
a number of important organic transformations. Among
a number of ion exchange resins tested, Amberlyst XN-
1010 and Amberlyst 15 complexed with lanthanides(III)
were the most effective catalysts. The simplification in
workup and separation of products and the recyclability
of the catalysts make the use of these novel catalysts a
promising alternative both in research laboratories and
in industrial processes.
Glycosyla tion w ith Glu cosyl F lu or id e in Alcoh ols
P r om oted by Ln -Resin s. Glycosyl fluorides have been
extensively utilized in constructing complicated oligosac-
charides, and accordingly, various Lewis acid promotors
have been developed to activate 1-fluoroglycosides.32
Most recently, lanthanides have been used as promotors
by Shibasaki et al.33 We found that Ln-resins, especially
Yb-XN1010 and Yb-Amberlyst 15, promoted glycosylation
of unprotected glucosyl fluoride in methanol (Table 8,
entries 9 and 10). It is noticed that methyl glucosides
are formed stereospecifically with complete inversion of
the anomeric chiral center of the glucosyl fluoride.
(30) (a) Moguro, M.; Asao, N.; Yamamoto, Y. J . Chem. Soc., Perkin
Trans. 1 1994, 2597. (b) Chini, M.; Crotti, P.; Favero, L.; Macchia, F.;
Pineschi, M. Tetrahedron Lett. 1994, 35, 433.
Exp er im en ta l Section
(31) Matsubara, S.; Onishi, H.; Utimoto, K. Tetrahedron Lett. 1990,
31, 6209.
(32) (a) Mukaiyama, T.; Murai, Y.; Shoda, S. Chem. Lett. 1981, 431.
(b) Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503 and references
cited therein.
(33) (a) Hosono, S.; Kim, W.; Sasai, H.; Shibasaki, M. J . Org. Chem.
1995, 60, 4-5. (b) Kim, W.; Hosono, S.; Sasai, H.; Shibasaki, M.
Tetrahedron Lett. 1995, 36, 25, 4443. (c) Kim, W.; Hosono, S.; Sasai,
H.; Shibasaki, M. Heterocycles 1996, 42, 795-809.
Gen er a l Rem a r k s. All unspecified reagents were from
commercial resources. Thin-layer chromatography was con-
ducted on EM silica gel 60 Si254F TLC plates with fluorescent
indicator. Column chromatography was conducted with silica
gel, grade 62, 60-200 mesh, 150 Å. All the products were
1
identified by H NMR and compared with literature data.

3580 J . Org. Chem., Vol. 62, No. 11, 1997
Yu et al.
Deter m in a tion of th e P r oton Exch a n ge Ca p a city of
Resin s. Dowex 50X-8 resins (100 g) were washed sequentially
with MeOH (200 mL), deionized water (200 mL), and HCl (1
M, 100 mL) with a flow rate of 2 mL/min in a column. Then
it was washed with water to neutral followed by drying
overnight in vacuo at 65 °C in the presence of P2O5. The dry
resins (W g) were stirred with an excessive standard solution
of NaOH (a mL, b M) in 20 mL of water for 4 h at 20 °C. The
NaOH remaining in solution was titrated with standard HCl
solution (c M). It consumed a volume (d mL) of HCl. The
acidic exchange capacity of the resins (EC) was calculated
according to the following formula:
yield: 34 1H NMR (CDCl3) δ 3.31 (6 H, s), 5.36 (1 H, s), 7.33 (1
H, d, J ) 8.4 Hz), 7.50 (1 H, d, J ) 8.4 Hz).
Acet a liza t ion of (S)-(-)-Cit r on ella l. Yb-Amberlyst 15
(100 mg), methanol (1 mL), trimethyl orthoformate (0.2 mL),
and (S)-(-)-citronellal (155 mg) were added to a 7 mL vial.
The mixture was shaken overnight. The resin was filtered
off and washed with methanol (2 mL × 3). The combined
organic solvents were removed in vacuo to give a residue,
which was purified to give (S)-(-)-citronellal acetal (6) (191
mg, 95% yield), eluting with hexane and ethyl acetate (9/1,
v/v):35 1H NMR (CDCl3) δ 0.92 (3 H, d, J ) 6.4 Hz), 1.19 (1 H,
m), 1.36 (1 H, m), 1.60 (3 H, s), 1.68 (3 H, s), 1.98 (1 H, m),
3.30 (3 H, s), 3.31 (3 H, s), 4.46 (1 H, t, J ) 6.6 Hz), 5.10 (1 H,
t, J ) 6.8 Hz).
EC ) (ab - cd)/W (mmol/g)
Ald ol Rea ction in Aqu eou s Solu tion : (i) Rea ction of
(1-Cycloh exen yloxy)t r im et h ylsila n e w it h F or m a ld e-
h yd e. (Cyclohexenyloxy)trimethylsilane (85 mg) was added
to a suspension of Yb-Amberlyst 15 (200 mg) in a mixture (2
mL) of THF (1.5 mL) and 37% aqueous formaldehyde (0.5 mL).
The reaction mixture was stirred at room temperature over-
night. The resin was filtered and washed with THF and water
(4/1, v/v). Water (10 mL) was added to the combined filtrate
followed by extraction with ethyl acetate three times. The
combined organic phase was washed with brine and dried over
anhydrous Na2SO4. The solvents were removed, and the
residue was purified via column chromatography eluting with
hexane and ethyl acetate (1/4, v/v) to give product 7 (61 mg)
in 81% yield:25c 1H NMR (CDCl3) δ 1.40-2.16 (m, 6 H), 2.25-
2.67 (m, 3 H), 3.55-3.63 (m, 1 H), 3.73 (dd, J ) 11.4, 7.2 Hz,
1 H).
Rea ction of (1-Cycloh exen yloxy)tr im eth ylsila n e w ith
Ben za ld eh yd e. Benzaldehyde (53 µL, 0.5 mmol) and cyclo-
hexenyltrimethylsilane (130 µL, 0.6) were added to a suspen-
sion of Yb-Nafion NR-50 (300 mg) in a mixture (1 mL) of THF
and water (4/1, v/v). The reaction mixture was stirred at rt
for 2 days. The resin was filtered and washed with THF.
Water (10 mL) was added to the combined filtrate followed by
extraction with ethyl acetate three times. The combined
organic phase was washed with brine and dried over anhy-
drous Na2SO4. The solvents were removed, and the residue
was purified through column chromatography. Two products
8, and 9, were collected together in a combined 43% yield. The
ratio (threo-8:erythreo-9, 4:1) was determined by proton NMR
analysis:25c 1H NMR (CDCl3) δ 5.39 (1 H, d, J ) 2.4 Hz, CHOH)
for 8, 4.89 (1 H, J ) 8.4 Hz, CHOH) for 9.
P r ep a r a tion of Na -Resin s fr om H-Resin s. Ion exchange
resin was packed in a column and washed with methanol and
water. Then the resin was washed with a saturated Na2SO4
solution until the eluent was neutral followed by three
washings with water. The resin was dried overnight in vacuo
at 65 °C in the presence of P2O5.
P r ep a r a tion a n d Deter m in a tion of La n th a n id e Con -
ten t of Ln -Resin s. The resin (W1 g) was placed into an
Erlenmeyer flask containing a solution of Ln2(SO4)3 (W1 mmol)
in water. Then the resulting mixture was stirred overnight.
The resin was filtered and washed with water three times.
The combined aqueous solution was transferred into a 100 mL
volumetric flask. The resin was washed with ethanol and
dried overnight in vacuo at 65 °C in the presence of P2O5. The
weight of the Ln resin was W2 g. The remaining amount of
lanthanide in the solution was determined by titration using
EDTA (0.0100 M) as a standard solution with xylenol orange
(sodium salt) as an indicator. From the above volumetric flask,
V1 mL of the solution was taken out and put into a 100 mL
Erlenmeyer containing a buffer of 20% hexamethylenetet-
raamine. Then the solution was titrated with an EDTA
solution with xylenol orange as indicator. The titration ended
as soon as the red color turned into yellow. It consumed V2
mL of the EDTA solution. The lanthanide content on the resin
was calculated as follows:
Ln content ) (2W1 - V2 × 0.01/V1 × 100)/W2 (mmol/g)
Rea ction of In d ole w ith Hexa n a l. A mixture (1 mL) of
ethanol and water (5/1, v/v), Ln-resin (200 mg), hexanal (100
mg, 1.0 mmol), and indole (235 mg, 2.0 mmol) was added to a
7 mL vial. The mixture was shaken for 12 h. The resin was
filtered and washed with ethanol three times. The combined
filtrate was concentrated in vacuo to give a residue, which was
purified via column chromatography eluting with ethyl acetate
and hexane (1/1, v/v) to give compound 1:14b 1H NMR (CDCl3)
δ 0.84 (3 H, t, J ) 7.2 Hz), 1.22-1.44 (6 H, m), 2.19 (2 H, m),
4.45 (1 H, t, J ) 7.6 Hz), 6.94 (2 H, d, J ) 2.4 Hz), 7.02 (2 H,
t, J ) 7.6 Hz), 7.13 (2 H, t, J ) 7.6 Hz), 7.28 (2 H, d, J ) 8.0
Hz), 7.58 (2 H, d, J ) 7.6 Hz), 7.84 (2 H, br, 2 NH); MS m/e
316 (M+).
Rea ction of a n Im in e w ith Silyl En ol Eth er 2. Silyl
ether 2 (0.7 mmol) and the imine (0.5 mmol) prepared from
aniline and benzaldehyde were added to a suspension of Yb-
XN1010 (200 mg) in dichloromethane. The reaction mixture
was stirred for 5 h. The resin was filtered and washed with
dichloromethane. The filtrate was concentrated in vacuo to
give a residue, which was purified through column chroma-
tography eluting with hexane and ethyl acetate (1/1, v/v) to
afford product 10 (129 mg) in 87% yield:26 1H NMR (CDCl3) δ
1.20 (3 H, s), 1.30 (3 H, s), 3.66 (3 H, s), 4.56 (1 H, s), 4.88 (1
H, br, NH), 6.53 (2 H, m), 6.63 (1 H, t, J ) 8.4 Hz), 7.06 (2 H,
m), 7.30 (5 H, m); MS m/e 297 (M+).
Ald ol Rea ction of Ben za ld eh yd e a n d Silyl Eth er 2 in
Dich lor om eth a n e. Ln-resin (200 mg), benzaldehyde (53 µL,
0.5 mmol), and 2 (121 µL, 0.6 mmol) were added to a 7 mL
vial containing 1 mL of dichloromethane. The reaction
mixture was shaken overnight. The resin was filtered and
washed with dichloromethane three times. To the filtrate was
added 0.1 mL of TFA, and the resulting solution was stirred
at room temperature for 10 min. After removal of solvent in
vacuo the residue was purified via column chromatography
Allyla tion of Hexa n a l w ith Tetr a a llyltin . Hexanal (125
µL, 1.0 mmol) and tetraallyltin (240 µL, 1.0 mmol) in water/
ethanol/toluene (1.2 mL, 1/7/4, v/v/v) was added to a solution
of Yb-Amberlyst 15 resin (250 mg). The suspension was
shaken at rt for 24 h in a sealed vial. The resin was filtered
and washed with ethanol (3 mL × 3). The filtrate was mixed
with 0.5 mL of 0.5 M HCl and stirred for 10 min. The solution
was extracted with ethyl acetate, and the organic phase was
washed with brine and dried over anhydrous MgSO4. After
removal of solvents, the residue was purified through column
chromatography eluting with hexane and ethyl acetate (8/2,
v/v) to give alcohol 11 (129 mg) in 91% yield.27a (NMR spectrum
is identical to that of the sample from Sigma): 1H NMR
(CDCl3) δ 0.91 (3 H, t, J ) 6.8 Hz), 1.32 (4 H, m), 1.46 (2 H,
m), 1.71 (1 H, br, OH), 2.14 (2 H, m), 2.30 (2 H, m), 2.30 (2 H,
eluting with ethyl acetate and hexane (1/4, v/v) to give 4:20 1
H
NMR (CDCl3) δ 1.09 (3 H, s), 1.13 (3 H, s), 3.70 (3 H, s), 4.88
(1 H, s), 7.29 (5 H, m); MS (m/e) 208 (M+).
Aceta liza tion of p-Br om oben za ld eh yd e. Yb-XN1010
(100 mg), dichloromethane (1 mL), trimethyl orthoformate (0.2
mL), and p-bromobenzaldehyde (100 mg) were added to a 7
mL vial. The mixture was shaken overnight. The resin was
filtered off and washed with dichloromethane (2 mL × 3). The
combined organic solvents were removed in vacuo to give
p-bromobenzaldehyde acetal (5) (124 mg) in a quantitative
(34) Davis, T. S.; Gattys, G. A.; Kubler, D. G. J . Org. Chem. 1976,
41, 2349.
(35) Stoll, M.; Bottle, P. Helv. Chim. Acta 1948, 31, 4.

Ln(III) Catalysts Supported on Ion Exchange Resins
J . Org. Chem., Vol. 62, No. 11, 1997 3581
m), 3.64 (1 H, m), 5.11 (1 H, m), 5.15 (1 H, s), 5.84 (1 H, m);
MS m/e 142 (M+).
Glycosyla tion of Glu cosyl F lu or id e in Alcoh ol. The Yb-
resin (200 mg) was immersed in 1 mL of methanol, and
R-glucosyl fluoride (50 mg) was added. The mixture was
stirred at rt until the starting material disappeared by TLC
monitoring. The resin was filtered and washed with methanol.
The filtrate was concentrated in vacuo to give a residue, which
was chromatographed eluting with ethyl acetate and ethanol
(5/2) to give methyl â-glucoside (16) (48 mg) in 89% yield:36
1H NMR (CD3OD) δ 3.15 (1 H, dd, J ) 9.2, 8.0 Hz), 3.28 (1 H,
m), 3.38 (2 H, m), 3.47 (3 H, s), 3.61 (1 H, dd, J ) 12.4, 6.0
Hz), 3.82 (1 H, dd, J ) 12.4, 2.4 Hz), 4.27 (1 H, d, J ) 8.4 Hz).
R-Glucosyl fluoride was replaced with â-glucosyl fluoride
and the same procedure was followed. The reaction gave
methyl R-glucoside (15) (46 mg) in 85% yield: 36 1H NMR (CD3-
OD) δ 3.28 (1 H, m), 3.30 (3 H, s), 3.43 (1 H, dd, J ) 10.0, 4.0
Hz), 3.53 (2 H, m), 3.63 (1 H, dd, J ) 12.0, 4.0 Hz), 3.74 (1 H,
s), 3.77 (1 H, m), 4.75 (1 H, m).
Aza Diels-Ald er Rea ction of Hexa n a l, Ben zyla m in e
Hyd r och lor id e, a n d Cyclop en ta d ien e. Yb-Amberlyst 15
(200 mg), water (1 mL), benzylamine hydrochloride (144 mg),
hexanal (100 mg), and cyclopentadiene (200 mg) were added
to a 7 mL vial. The mixture was shaken for 2 days. The resin
was filtered and washed with water. The combined solution
was extracted with ethyl acetate (5 mL × 3). The combined
organic phase was neutralized with ammonia. The solvent
was removed, and the residue was purified to give exo product
12 in 35% yield:14a 1H NMR (CDCl3) δ 0.86 (t, J ) 6.4 Hz, 3
H), 1.28 (m, 8 H), 1.42 (m, 1 H), 1.61 (d, J ) 8.4 Hz, 1 H), 1.69
(d, J ) 8.4 Hz, 1 H), 2.61 (s, 1 H), 3.30 (d, J ) 12.4 Hz, 1 H),
3.43 (d, J ) 12.4 Hz, 1 H), 3.65 (s, 1 H), 6.08 (m, 1 H), 6.42 (m,
1 H), 7.29 (m, 5 H).
Rin g-Op en in g Rea ction of 1,2-Ep oxyocta n e in Meth a -
n ol. A 7 mL vial containing methanol (1 mL) was added to
Yb-Amberlyst 15 and 1,2-epoxyoctane (128 mg). The reaction
mixture was shaken for 20 h. The resin was filtered off, and
the filtrate was condensed in vacuo to give a residue. Two
isomers, 13 and 14, were isolated through column chroma-
tography. The ratio of 1-methoxy-2-octanol (13) to 2-methoxy-
1-octanol (14) was 1.7:1 with a combined yield of 97%. 13:
1H NMR (CDCl3) δ 0.89 (3 H, t, J ) 7.5 Hz), 1.31 (m, 8 H),
1.46 (1 H, m), 1.58 (1 H, m), 3.26 (1 H, m), 3.41 (3 H, s), 3.46
(1 H, m), 3.68 (m, 1 H). 14: 1H (CDCl3) δ 0.88 (3 H, t, J ) 7.2
Hz), 1.29 (m, 8 H), 1.44 (2 H, m), 3.23 (1 H, dd, J ) 9.2, 8.0
Hz), 3.39 (s, 3 H), 3.41 (m, 1 H), 3.77 (1 H, m).
Ack n ow led gm en t. The authors thank Hercules Inc.
for financial support of this work. We are also grateful
to Drs. H.-N. Cheng, Robert G. Nickol, and Brian J .
Swetlin for helpful discussions.
J O961933+
(36) J ansson, P.-E.; Kenne, L.; Schweda, E. J . Chem. Soc., Perkin
Trans. I 1987, 377.