Ytterbium trifluoromethanesulfonate Yb(OTf)3: An efficient, reusable catalyst for highly selective formation of β-alkoxy alcohols via ring-opening of 1,2-epoxides with alcohols

Article abstract of DOI:10.1055/s-2001-14909

Ytterbium(III)triflate-catalysed ring-opening reactions of epoxides derived from styrene, cyclohexene, norbornene and stilbene, in the presence of alcohols (C₁-C₄ 1°, 2° and 3° aliphatic alcohols, cyclohexyl alcohol, allyl and propargyl alcohol) resulted in the formation of β-alkoxy alcohols in good to excellent yield with high regio-, and, where applicable, stereoselectivity. Reaction of stilbene oxide with methanol in the presence of the diethyl ester of L-(+)-tartaric acid afforded the threo form of 1,2-diphenyl-2-methoxy ethanol with high diastereoselectivity (de 94%). Mechanistic implications of the results are discussed.

Full text of DOI:10.1055/s-2001-14909

836
LETTER
Ytterbium Trifluoromethanesulfonate Yb(OTf)3: An Efficient, Reusable
Catalyst for Highly Selective Formation of -Alkoxy Alcohols via Ring-
Opening of 1,2-Epoxides with Alcohols1
Pravin R. Likhar, Manyam Praveen Kumar, Ananda K. Bandyopadhyay*
Metalorganic Laboratory, Inorganic Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91-40-717-0921; E-mail: akbandyopadyay@iict.ap.nic.in
Received 4 April 2001
oxides with a variety of alcohols has been investigated,
Abstract: Ytterbium(III)triflate-catalysed ring-opening reactions
the results of which are communicated here.
of epoxides derived from styrene, cyclohexene, norbornene and stil-
bene, in the presence of alcohols (C1-C4 1o, 2o and 3o aliphatic alco-
Reaction of epoxides (1a, 1b, 4 and 6) with alcohols in the
hols, cyclohexyl alcohol, allyl and propargyl alcohol) resulted in the
presence of Yb(OTf)3 proceeds smoothly under mild con-
formation of -alkoxy alcohols in good to excellent yield with high
ditions in neat alcohol as the solvent or with alcohol in a
regio-, and, where applicable, stereoselectivity. Reaction of stilbene
suitable solvent, with near quantitative conversion in a
oxide with methanol in the presence of the diethyl ester of L-(+)-tar-
short duration of time and with a high degree of regio-
taric acid afforded the threo form of 1,2-diphenyl-2-methoxy etha-
nol with high diastereoselectivity (de 94%). Mechanistic
implications of the results are discussed.
and, where applicable, stereoselectivity (Equations 1a-c):
Key words: ytterbium triflate catalyst, ring-opening of epoxide,
-alkoxy alcohol, diastereoselective reaction, eco-friendly process
OR
O
Ph
H
H
Ph
Yb(OTf)3
H
ROH
+
H
R'
R'
OH
R = Me
Ring-opening reactions of 1,2-epoxides with alcohols un-
der catalytic conditions provide uniquely important syn-
thetic methodology for preparation of -hydroxy ethers,
which are valuable solvents,2 natural products3 and inter-
mediates for -alkoxy ketones and -alkoxy acids. As a
result, there has been long-standing interest in developing
efficient and versatile protocols that give convenient ac-
cess to -hydroxy ethers.4 Early attempts of alcoholysis of
epoxides under acidic or basic conditions suffer from high
temperature requirements which consequently result in
extensive polymerization and low regioselectivity.5 In re-
cent years, various approaches have been made to bring
about the transformation under milder conditions. During
this eventful period Nafion-H,5 dehydrated alumina,6 ben-
tonite clay,7 organotin phosphate condensates,8 alkali and
2a
2b
2c
R' = H, R = Me
R' = H, R = Et
R' = H, R = n-Pr
R' = H, R = i-Pr
R' = H, R = n-Bu
R' = H, R = i-Bu
R' = H, R = t-Bu
R' = H, R = cyclohexyl
R' = H, R = allyl
3a
3b
3c
3d
3e
3f
3g
3h
3i
R' = H 1a
Ph 1b
Et
n-Pr
i-Pr
n-Bu
i-Bu
t-Bu
cyclohexyl
2d
2e
2f
2g
2h
2i
2j
allyl
propargyl
3j
3k
R' = H, R = propargyl
R' = Ph, R = Me
Equation 1a
OH
OR
Yb(OTf)3
+
ROH
O
alkaline
earth
metal
salts,9
iodine-PVP
R = Me
5a
R = Et 5b
4
R = Me 2a
(PVP = polyvinylpyrrolidone)10 and one-electron transfer
reagents11,12 are reported as effective catalysts or promot-
ers for alcoholysis of epoxides under neutral conditions.
However, the reported procedures have limitation(s) in
one way or other thereby restricting their wide-spread ap-
plicability. Thus, high acidity,5 high reaction tempera-
ture,9,13 prolonged reaction time,9,14 critical handling of
catalysts,6,8 unsatisfactory selectivity,5,9 and non-catalytic
nature of the reagent9 are unfavourable factors. Moreover,
no attempt has been made to recycle the catalyst, thereby
making the process more eco-friendly.
Et
2b
Equation 1b
OH
Yb(OTf)3
MeOH
+
O
OMe
exo-norbornene oxide
7
6
Equation 1c
Lanthanide trifluoromethanesulfonates (triflates) have
emerged as novel Lewis acid catalysts that can effect nu-
merous reactions, thus unfolding new applications in or-
ganic synthesis.15 As a part of our continued effort to
explore unique reactivity of lanthanide salts,16 ytterbi-
um(III)triflate-catalysed ring-opening reaction of 1,2-ep-
In a typical run epoxide (1.0 mmol) is added to a stirred
solution of anhydrous ytterbium(III) trifluoromethane-
sulfonate (1 mg, 0.17 mol% based on epoxide) in dry and
freshly distilled alcohol (7.0 mL). The stirring is contin-
Synlett 2001, No. 6, 836–838 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Ytterbium Trifluoromethanesulfonate as an Efficient, Reusable Catalyst
837
Table Yb(OTf)3-Catalysed Reaction of 1,2-Epoxides with Alco-
ued at the reaction temperature for the required period
(monitored by TLC). After removal of solvents using a ro-
tavapor the residual mass is washed with water, the organ-
ic content is extracted with ethyl acetate (20 mL) and is
dried over anhydrous sodium sulfate. Partial evaporation
of the solvent followed by separation on a short silica gel
column (1.5 5 cm 60-120 mesh, petroleum ether/ethyl
acetate 94/6 as eluent) affords analytically pure -alkoxy
alcohol. The isolated yields are calculated on the basis of
the amount of epoxides used and 98-99% mass balance is
hols to form -Alkoxy Alcoholsa
1
obtained. The products are fully characterised by H
NMR, MS and for newly reported compounds, by C, H
analyses. The results obtained with some representative
epoxides are summarised in the Table. The Table shows
that in the presence of the catalyst, as low as 0.2 mol%, the
epoxides undergo facile reaction with various classes of
alcohols namely, aliphatic 1o, 2o, and 3o alcohols 2a-2g,
cyclic alcohol 2h and unsaturated alcohols 2i, 2j with ex-
cellent to good yield (entries 1-10). However, the reac-
tions with unsaturated alcohols are performed at the reflux
temperature of dichloromethane. When the reaction is
performed under identical conditions but in the absence of
Yb(OTf)3, 1a is recovered entirely unreacted (entry 15).
aReaction conditions: substrate epoxide (1.0 mmol), alcohol (7.0 ml)
otherwise mentioned. bProducts are characterised either on the basis
of spectroscopic data reported elsewhere9 or reported here. cIsolated
yield based on epoxide, values within parenthesis refer to GLC
1
yield.17 dLiquid; H NMR (CDCl3) : 7.2-7.4 (m, 5H), 4.3-4.4 (dd,
1H, J = 9.8 and 5.07 Hz), 3.5-3.65 (m, 2H), 3.25-3.4 (m, 2H), 2.5 (br,
OH) 1.5-1.7 (sextet, 2H, J = 7.78 Hz), 0.9 (t, 3H, J = 9.86 Hz); EIMS
e
1
e/z: 180. Liquid; H NMR (CDCl3) : 7.2 (s, 5H), 4.2-4.3 (dd, 1H,
J = 8.7 and 5.12 Hz), 3.4-3.6 (m, 2H), 3.2-3.35 (m, 2H), 2.69 (br, 1H),
1.4-1.55 (m, 2H), 1.2-1.4 (m, 2H), 0.8 (t, 3H, J = 8.7 Hz); EIMS e/z:
Products 3a-3j are identified as 2-alkoxy-2-phenyl etha-
nol by oxidation to the corresponding aldehyde, which
demonstrates that the epoxide 1a undergoes a completely
regioselective ring-opening under the influence of the cat-
alyst (Equation 1a). A similar facile reaction of 4 with al-
cohols affords trans-hydroxy ethers 5a and 5b in excellent
yield signifying that the reaction is highly anti-stereose-
lective (Equation 1b). However, the product obtained
from the reaction of 6 with MeOH resulted in a mixture of
exo- and endo-OMe isomers in the ratio 70:30, as deter-
mined by 1H NMR (Equation 1c). The results are obvious
consequence of the involvement of a carbocation interme-
diate.9,12 In the case of styrene oxide 1a the benzylic cat-
ion, being far more stabilised than the primary
carbocation,19 becomes the favourable site for the nucleo-
philic attack, thus giving rise to the formation of 2-alkoxy-
f
1
194. Liquid; H NMR (CDCl3) : 7.3 (m, 5H), 4.45-4.55 (dd,1H,
J = 9.04 and 4.76 Hz), 3.3-3.5 (m, 1H), 3.5-3.6 (m, 2H), 2.4 (br, 1H),
1.3-1.8 (m, 2H), 1.17 (d, 1H, J = 7.85 Hz), 1.05 (d, 1H, J = 8.0 Hz),
1.0-0.8 (m, 3H); EIMS e/z: 193. gLiquid; 1H NMR (CDCl3) : 7.3 (s,
5H), 4.5 (dd, 1H, J = 10.24 and 5.12 Hz), 3.55 (d, 2H, J = 5.6 Hz),
3.25 (m, 1H), 2.2 (br, 1H), 1.95 (m, 1H), 1.7 (m, 3H), 1.1-1.6 (m, 5H);
EIMS e/z: 220. hEpoxide (1.0 mmol), alcohol (2.0 mmol), methylene
chloride (7.0 ml). iLiquid; 1H NMR (CDCl3) : 7.25-7.4 (m, 5h), 5.8-
6.05 (m, 1H), 5.15-5.35 (m, 2H), 4.5 (dd, 1H, J = 8.72 and 4.18 Hz),
3.95-4.1 (m, 1H), 3.6-3.9 (m, 4H); EIMS e/z: 178. jLiquid; 1H NMR
(CDCl3) : 7.25-7.4 (m, 5H), 4.65 (dd, 1H, J = 9.21 and 5.63 Hz), 4.2
(dd, 1H, J = 15.88 and 2.56 Hz), 3.95 (dd, 1H, J = 15.88 and 2.56
Hz), 3.5-3.8 (m, 2H), 2.4 (t, 2H, J = 1.7 Hz); EIMS e/z: 176. kLiquid;
1H NMR (CDCl3) : 3.35 (s, 3H), 2.75-2.85 (m, 1H), 1.9-2.0 (m, 2H),
1.0-1.4 (m, 5H). EIMS e/z: 130. lExo-OMe:endo-OMe = 70:30 (by
1H NMR); EIMS e/z: 142. mCatalyst, recycled after single use, is
2-phenyl ethanol 3a-3j with essentially complete regiose- employed18. Solid; H NMR (CDCl3) : 7.3 (m, 10H), 4.9 (d, 1H,
lectivity. In the case of trans-stilbene oxide 1b the product
3k is obtained as mixture of two diastereoisomers in the
n
1
J = 3.5 Hz), 4.35 (d, 1H, J = 2.50 Hz), 3.25 (s, 3H), 2.3 (s, 1H) (threo
isomer); 7.3 (m, 10H), 4.7 (d, 1H, J = 9.34 Hz), 4.1 (d, 1H, J = 9.86
Hz), 3.35 (s, 3H), 2.5 (s, 1H) (erythro isomer); EIMS e/z: 228.
racemic form with a modest diastereoselectivity, as deter-
mined by 1H NMR20 and chiral HPLC21
(threo:erythro = 71:29, entry 16). The formation of two
diastereoisomers is again indicative of a dissociative
mechanism. The ratio threo:erythro is found to be virtual-
ly unaltered (within experimental error) when the reaction
is quenched at lower conversion level (40%, GLC). Fur-
thermore, a pure sample of the threo isomer (racemic mix-
ture) of 1,2-diphenyl-2-methoxy ethanol does not undergo
transformation to the erythro form under the experimental
conditions. Thus, the possibility of isomerisation of the
product by the influence of the catalyst is ruled out. When
1b is allowed to react with methanol in the presence of
L-(+)-diethyl tartrate (3 equivalents with respect to the
catalyst) under otherwise identical conditions, high dias-
tereoselectivity (threo:erythro = 97:3) is observed.21 Here
oThreo:erythro = 71:29 (determined by 1H NMR and by chiral
HPLC20).
again, both the isomers are formed as racemic mixtures.
The observed results can be plausibly explained by an in-
termediate complex formation between the epoxide and
chiral Lewis acid catalyst, in which the subsequent ap-
proach of the nucleophile is preferred form one face (at-
tack A in the Scheme). This results in an apparent
diastereo face differentiation. The reusability of the cata-
lyst has been tested by exposing the catalyst, isolated from
the reaction mixture (cf. Table, entry 2),18 to a fresh batch
of 1a under identical reaction conditions (entry 14) with
the yield of the product 3b remaining virtually unaltered
(within the experimental error).
Synlett 2001, No. 6, 836–838 ISSN 0936-5214 © Thieme Stuttgart · New York

838
P. R. Likhar et al.
LETTER
(3) Corey, E. J.; Cheng, X. M. The Logic of Chemical Synthesis,
John Wiley, New York, 1989.
A
Threo-isomers
(4) Rosowski, A. in Heterocyclic Compounds with Three- and
Four-Membered Rings, Part I, Weissberger, A., Ed.,
Interscience Publishers, New York, 1964.
(5) Olah, G. A.; Fung, A. P.; Meider, D. Synthesis 1981, 280.
(6) Posner, G. H.; Rogers, D. Z. J. Am. Chem. Soc. 1977, 99,
8208.
(7) Cabrera, A.; Rosas, N.; Marquez, C.; Salmon, M.; Angeles,
E.; Miranda, R.; Lozano, R. Gazz. Chim. Ital. 1991, 121, 127.
(8) (a) Niibo, Y.; Nakata, T.; Otera, J.; Nozaki, H. Synlett 1991,
97. (b) Otera, J.; Niibo, Y.; Nozaki, H. Tetrahedron 1991, 47,
7625.
[YbLn*]
O
(Favoured)
+
..
Ph
ROH
C
C
..
H
H
Ph
Erythro-isomers
B
Diastereo face differentiation in the presence of chiral ligand L*
(9) Chini, M.; Crotti, P.; Gardelli, C.; Macchia, F. Synlett 1992,
673.
Scheme
(10) Iranpoor, N.; Tamami, B.; Niknam, K. Can. J. Chem. 1997,
75, 1913.
(11) Iranpoor, N.; Mohammadpour Baltork, I. Synth. Commun.
1990, 20, 2789.
(12) Iranpoor, N.; Salehi, P. Synthesis 1994, 1152.
(13) Iranpoor, N.; Mohammadpour Baltork, I. Tetrahedron Lett.
1990, 31, 735.
(14) Posner, G. H.; Rogers, D. Z.; Kinzig, C. H.; Gurria, G. M.
Tetrahedron Lett. 1975, 31, 3591.
(15) Xie, W.; Jin, Y.; Wang, P. G. Chemtech 1999, 29, 23.
(16) Likhar, P. R.; Bandyopadhyay, A. K. Synlett 2000, 538.
(17) Shimadzu GC-14B equipped with flame ionization detector
and SE 30 packed column.
(18) The yitterbium triflate catalyst was recovered from the
reaction mixture (cf. entry 2) by following the procedure
described in ref. 16. The isolated solid, thus obtained, is dried
under high vacuum at 50 °C for 6 h and is employed in the
recycle experiment (entry 14).
In conclusion, a simple highly efficient method for the
preparation of -alkoxy alcohol is presented, which oper-
ates under mild conditions via regio- and stereoselective
ring opening of 1,2-epoxides by using easily recyclable
Yb(OTf)3 as a Lewis acid catalyst. The procedure is ap-
plied successfully to unsaturated alcohols and, because of
the mild conditions, is expected to be safe for substrates
that contain delicate functionalities. Furthermore, it ap-
pears to be attractive from environmental standpoint. In
addition, the results are significant as they lend experi-
mental support to the mechanism of Lewis acid-catalysed
nucleophilic ring-opening of epoxides envisaged earlier.22
Acknowledgement
(19) Bruice, P. Y. Organic Chemistry, Prentice Hall: New Jersey,
1995, p286.
Authors are grateful to Director IICT for financial support (MLP-
2711) of this work and to the Department of Science and Technolo-
gy, New Delhi for funding the purchase of GLC equipment (Grant
No. SP/S1/F11/97). Technical assistance of K. Venkat Ramana is
thankfully acknowledged.
(20) Hassner, A.; Reuss, R. H. J. Org. Chem. 1974, 39, 553.
(21) Shimadzu LC-6A system controller, SPD-6A fixed-
wavelength UV monitor as detector, FCV-100B fraction
collector, Diacel chiral OD column, hexane/iso-propanol (85/
15), flow rate is 0.5 mL, 254 nm.
(22) Mori, S.; Nakamura, E.; Morokuma, K. J. Am. Chem. Soc.
2000, 122, 7294.
References and Notes
(1) IICT communication no. 4683.
(2) March, J. Advanced Organic Chemistry, 3rd ed., John Wiley,
New York, 1985, p. 346.
Article Identifier:
1437-2096,E;2001,0,06,0836,0838,ftx,en;D00301ST.pdf
Synlett 2001, No. 6, 836–838 ISSN 0936-5214 © Thieme Stuttgart · New York