Copper(II) tetrafluoroborate catalyzed ring-opening reaction of epoxides with alcohols at room temperature

Article abstract of DOI:10.1021/ol025997k

(figure presented) Efficient ring opening of different epoxides by reaction with representative alcohols is presented. These processes were carried out at room temperature and rely on the usefulness of commercial copper tetrafluoroborate as catalyst.

Full text of DOI:10.1021/ol025997k

ORGANIC
LETTERS
2002
Vol. 4, No. 17
2817-2819
Copper(II) Tetrafluoroborate Catalyzed
Ring-Opening Reaction of Epoxides with
Alcohols at Room Temperature
Jose´ Barluenga,* Henar Va´zquez-Villa, Alfredo Ballesteros, and Jose´ M. Gonza´lez
Instituto UniVersitario de Qu´ımica Organometa´lica “Enrique Moles”-Unidad Asociada
al C.S.I.C., UniVersidad de OViedo, OViedo 33071, Spain
barluenga@sauron.quimica.unioVi.es
Received April 10, 2002 (Revised Manuscript Received July 17, 2002)
ABSTRACT
Efficient ring opening of different epoxides by reaction with representative alcohols is presented. These processes were carried out at room
temperature and rely on the usefulness of commercial copper tetrafluoroborate as catalyst.
Alcohols behave as poor nucleophilic reagents in substitution
processes. Nevertheless, under strongly acidic or basic
conditions1 their use for ring-opening reactions of epoxides2
is well established and provides a powerful entry to
â-alkoxyalcohols.3 The harsh conditions associated with those
procedures have spurred a search for new and mild meth-
odologies. Major attempts have focused on testing different
heterogeneous conditions. Significant advances have been
accomplished; however, the reported scope of this approach
is constrained at room temperature to only primary alcohols.4
Thus, there is ongoing activity aimed to establish a more
general, simple, and efficient catalytic protocol to accomplish
this transformation.5 Herein, we report on the use of
commercial hydrated copper(II) tetrafluoroborate as a more
suitable and convenient catalyst to induce ring-opening
reactions of epoxides by incorporation of a set of representa-
tive alcohols, in all cases at room temperature.
Our initial studies showed that Cu(BF4)2‚nH2O (1) is an
adequate catalyst for the ring opening of cyclohexene oxide
2 by methanol 3. A single adduct, trans-2-methoxycyclo-
hexanol 46 (71% isolated yield) was obtained upon reaction
for 1 h at room temperature of 2 (5 mmol) with 3 (20 mL),
in the presence of 10 mol % of the catalyst. Interestingly,
further experiments showed that the amount of both alcohol
and catalyst can be lowered without affecting the perfor-
mance of the process at room temperature. Overall, these
facts establish a sharp difference with respect to the already
reported features of alternative methodologies. The process
can be efficiently conducted on a 100 mmol basis of 2, using
1 mmol of catalyst (0.01 equiv with respect to 2). The
(1) (a) Smith, III, A. B.; Liverton, N. J.; Hrib, N. J.; Sivaramakrishnan,
H.; Winzenberg, K. J. Am. Chem. Soc. 1986, 108, 3040-3048. (b) Izumi,
Y.; Hayashi, K. Chem. Lett. 1980, 787-790. (c) Stamm, H.; Mall, T. J.
Org. Chem. 1987, 52, 4812-4814.
(2) For a review, see: Smith, J. G. Synthesis 1984, 629-656.
(3) (a) Stead, P.; Marley, H.; Mahmoudian, M.; Webb, G.; Noble, D.;
Ip, Y. T.; Piga, E.; Rossi, T.; Roberts, S.; Dawson, M. J. Tetrahedron:
Asymmerty 1997, 7, 2247-2250. (b) Xin, J.; Suo, J.; Zhang, X.; Zhang, Z.
New J. Chem. 2000, 24, 569-570. (c) Salomon, C. J. Synlett 2001, 65-68
and references therein.
(4) Posner, G. H.; Rogers, D. Z. J. Am. Chem. Soc. 1977, 99, 8208-
8214. (b) Olah, G. A.; Fung, A. P.; Meidar, D. Synthesis 1981, 280-282.
(c) Otera, J.; Niibo, Y.; Tatsumi, N.; Nozaki, H. J. Org. Chem. 1988, 53,
275-278. (d) Hodson, L. F.; Parker, T. M.; Whittaker, D. J. Chem Soc.,
Chem. Commun. 1993, 1427-1428.
(5) (a) Guivisdalsky, P. N.; Bittman, R. J. Am. Chem. Soc. 1989, 111,
3077-3079. (b) Iranpoor, N.; Baltork, I. M. Synth. Commun. 1990, 20,
2789-2797. (c) Chini, M.; Crotti, P.; Gardelli, C.; Macchia, F. Synlett 1992,
673-676. (d) Iranpoor, N.; Salehi, P. Synthesis 1994, 1152-1154. (e)
Iranpoor, N.; Zardaloo, F. S. Synth. Commun. 1994, 24, 1959-1969. (f)
Masaki, Y.; Miura, T.; Ochiai, M. Bull. Chem. Soc. Jpn. 1996, 69, 195-
205. (g) Choudary, B. M.; Sudha, Y. Synth. Commun. 1996, 26, 2989-
2992. (h) Iranpoor, N.; Shekarriz, M.; Shiriny, F. Synth. Commun. 1998,
28, 347-366. (i) Iranpoor, N.; Zeynizadeh, B. Synth. Commun. 1999, 29,
1017-1024. (j) Prestat, G.; Baylon, C.; Heck, M.-P.; Mioskowski, C.
Tetrahedron Lett. 2000, 41, 3829-3831. (k) Mohammadpoor-Baltork, I.;
Tangestaninejad, S.; Aliyan, H.; Mirkhani, V. Synth. Commun. 2000, 30,
2365-2374.
(6) All the reported ring-opened epoxide derivatives gave analytical and
spectroscopic data in agreement with the proposed structures.
10.1021/ol025997k CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/01/2002

Table 1. Room-Temperature Alcoholysis of Epoxides Catalyzed by Cu(BF4)2‚nH2O (1)
a 25 mmol of epoxide was used. b 4 equiv of alcohol was used per equiv of epoxide c Based on isolated compounds and referred to epoxide. d 20% of
unreacted 14 was recovered. e 19 was obtained in near 70% yield upon reaction for 6 h. f Combined yield from isolated amounts of pure 20 (34%) and 21
(26%), after separation by column chromatography on silica gel (hexane/ethyl acetate 10/1, as eluent). g Based on GC analysis of the crude reaction mixture,
for 1.3:1 molar ratio 20:21, respectively.
reaction has been optimized using a 1:4 molar ratio of 2:3,7
to yield 4 in nearly quantitative isolated yield (Scheme 1)
after reacting for 2 h at room temperature in CH2Cl2 (60
mL).
These results nicely prove that derivatives of labile primary
alcohols, such as benzylic and allylic systems, are easily
prepared following this approach. Similarly, compounds
incorporating more hindered hydroxyl functionalies are
conveniently synthesized through this mild and simple
approach. In each case, products were obtained as single
diastereoisomer having trans stereochemistry.
The influence of the epoxide over the outcome of the
reaction was also tested (see Table 1). Linear epoxides 14
and 15 give information about the regiochemistry of the
opening reaction. The epoxide 14 led always to the formation
of one regiosomer, incorporating the alcohol at the phenyl-
Scheme 1. Optimized Conditions for the
Cu(BF4)2‚nH2O-Catalyzed Ring-Opening Methanolysis of
Cyclohexeneoxide
Scheme 2. Alcohol Compatibility
The influence of the substitution pattern on the alcohol
was tested, and the results are summarized in Scheme 2.
Along this series,8 25 mmol of epoxide 2 was subjected to
reaction under the conditions above outlined for methanol.
(7) The use of lower values of alcohol-to-epoxide ratio gave rise to
competitive formation of several epoxide oligomers. Thus, when the reaction
was run adding 2 equiv of 3 per equiv of 2, adduct 4 was isolated in 40%
yield; in addition, a compound of formula HO-C6H10-O-C6H10-OCH3 was
isolated in 10% yield, along a mixture of several other oligomers.
(8) One mole percent of 1 and 20 mL of CH2Cl2 were routinely
employed.
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Org. Lett., Vol. 4, No. 17, 2002

substituted carbon, irrespectively of the nature of the alcohol,
as expected for a charge-controlled ring-opening process.9
However, for the alkyl-substituted system 15, two adducts
were obtained upon reaction with methanol in the presence
of 1.10 Products 20 and 21were formed at room temperature
in a 1.3:1 molar ratio, respectively. They reflect the expected
competition of opening pathways for this type of epoxide.11
The reaction temperature was tested in an attempt to
modulate the regiochemistry of the process. At -40 °C a
more sluggish reaction takes place, requiring longer reaction
time to be completed, but without major impact over the
selectivity.
formation of 23 as sole reaction product in 65% isolated yield
was noticed (on a 4 mmol basis of 22, using 1:4 molar ratio
of 22:3).
The assigned structure for 23 is based on its analytical
and spectroscopic data. 2D-HMQC, 2D-HMBC, and NOESY
experiments were determinant to establish the regiochemistry
and to elucidate the stereochemistry. The observed stereo-
chemistry bodes well with that previously reported for ring-
opening reactions of 22 by water, and more recently by
morpholine.13
In summary, an efficient method at room temperature for
the ring-opening reaction of epoxides by a wide set of
representative alcohols is reported. The procedure takes place
under very mild conditions and relies simply on the addition
of catalytic amounts of a cheap and commercial copper salt.
The process is easily able to transform 0.1 mol of epoxide,
features a nice and predictable selectivity, and eventually
might have additional interest to broach new approaches to
the as yet elusive enantioselective desymmetryzation14 reac-
tion of achiral epoxides with alcohols.15 Work is in progress
to explore this possibility.
Furthermore, the reaction of an enantiopure epoxide
derived from the chiral pool was tested (Scheme 3). Epoxide
Scheme 3. Derivatives from (+)-3-Carene
Acknowledgment. We thank Spanish DGES (PB97-
1271) for financial support.
Supporting Information Available: General experimen-
1
tal procedure, characterization data (copies of H and 13C
22 was prepared from commercial (+)-3-carene in one step12
and subjected to reaction with methanol under the general
conditions already established. It is also a challenging
substrate that proves the opening of a more substituted
epoxide. Upon reaction for 6 h at room temperature, the
NMR spectra of â-alkoxyalcohols reported), and full char-
acterization data for compound 23. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL025997K
(13) For the MgBr2-promoted reaction, the amino alcohol derivative
obtained also holds a trans relationship for these two functional groups;
however, the opposite regioisomer was formed. See: Kauffman, G. S.;
Harris, G. D.; Dorow, R. L.; Stone, B. R. P.; Parsons Jr., R. L.; Pesti, J. A.;
Magnus, N. A.; Fortunak, J. M.; Confalone, P. N.; Nugent, W. A. Org.
Lett. 2000, 2, 3119-3121.
(9) Lewars, E. G. In ComprehensiVe Heterocyclic Chemistry; Katritzky,
A. R., Rees, C. W., Lwowski, W., Eds.; Pergamon: Oxford, 1984; Vol. 7;
Chapter 5, pp 100-113.
(10) The fact that 15 reacts under these conditions establishes a marked
contrast with the previously noticed unreactivity of alkyl-substituted terminal
epoxides in copper(II)-catalyzed opening reaction in the presence of acetone
at 60 °C; see: Hanzlik, R. P.; Leinwetter, M. J. Org. Chem. 1978, 43,
438-440.
(11) (a) Rao, A. S.; Paknikar, S. K.; Kirtane, J. G. Tetrahedron 1983,
39, 2323-2367. (b) Eisch, J. J.; Liu, Z.-R., Ma, X.; Zheng, G.-X. J. Org.
Chem. 1992, 57, 5140-5144.
(12) For the preparation of 22 and studies on its ring opening by water,
see: Brown, H. C.; Suzuki, A. J. Am. Chem. Soc. 1967, 89, 1933-1941.
(14) For reviews, see: (a) Hodgson, D. M.; Gibbs, A. R.; Lee, G. P.
Tetrahedron 1996, 52, 14361-14384. (b) Jacobsen, E. N. Acc. Chem. Res.
2000, 33, 421-431.
(15) For the first examples of intermolecular kinetic resolution of
epoxides with alcohols catalyzed by metal complexes, see: Ready, J. M.;
Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 2687-2688. For related recent
work, see: Ready, J. M.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2002, 41,
1374-1377.
Org. Lett., Vol. 4, No. 17, 2002
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