Highly efficient Meinwald rearrangement reactions of epoxides catalyzed by copper tetrafluoroborate

Article abstract of DOI:10.1016/j.tetlet.2006.06.055

Epoxides undergo a highly efficient and selective rearrangement in the presence of catalytic quantities of copper tetrafluoroborate to give carbonyl compounds in excellent yields. The low toxicity and ease of handling of this reagent make it an attractive alternative to the more corrosive Lewis acids frequently employed.

Full text of DOI:10.1016/j.tetlet.2006.06.055

Tetrahedron Letters 47 (2006) 5919–5921
Highly efficient Meinwald rearrangement reactions
of epoxides catalyzed by copper tetrafluoroborate
Mathew W. C. Robinson, Kathryn S. Pillinger and Andrew E. Graham*
Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK
Received 16 May 2006; revised 1 June 2006; accepted 8 June 2006
Available online 30 June 2006
Abstract—Epoxides undergo a highly efficient and selective rearrangement in the presence of catalytic quantities of copper tetra-
fluoroborate to give carbonyl compounds in excellent yields. The low toxicity and ease of handling of this reagent make it an
attractive alternative to the more corrosive Lewis acids frequently employed.
ꢀ 2006 Elsevier Ltd. All rights reserved.
The rearrangement of epoxides to produce carbonyl
compounds (the Meinwald rearrangement) has attracted
considerable interest in recent years, given the efficiency
of the rearrangement and the synthetic and industrial
utility of this process (Scheme 1).1 A number of factors
have been identified as critical in determining the product
distribution of this reaction, such as the migratory apti-
tude of the epoxide substituents, the Lewis acid catalyst
utilized and the solvent employed.2 Typically, if there is
no structural bias, a mixture of products is produced
due to the lack of regioselectivity in the ring opening pro-
cess. Hence, there has been considerable interest in the
development of Lewis acids that display enhanced selec-
tivity and which are efficient in catalytic quantities.
or methylaluminium bis(4-bromo-2,6-di-tert-butylphen-
oxide) (MABR)3 have all proven to be useful, however,
the reagents are typically employed in stoichiometric
quantities. More recent protocols employing catalytic
quantities of Lewis acids such as palladium salts, indium
trichloride, iridium trichloride, bismuth salts and gal-
lium salts have all proven to be efficient.4 There remain,
however, limitations to these protocols whether it be a
lack of selectivity, the toxic or corrosive nature of the
catalyst employed, the production of addition or poly-
meric products or the requirement to employ expensive
rare metals. Recently, while investigating addition reac-
tions to epoxides catalyzed by copper tetrafluoroborate
(Cu(BF4)2ÆnH2O), we noted that epoxides underwent a
highly efficient rearrangement process to produce car-
bonyl products. We were surprised to discover that there
had only been one reported example of the use of cop-
per(II) salts to catalyze epoxide rearrangement reac-
tions5,6 and this prompted us to initiate further studies
in this area, the results of which are summarized in
Table 1.
The originally reported procedures utilizing boron triflu-
oride diethyletherate, lithium salts, magnesium bromide
O
R1
R2
H
LA
O
R3
The rearrangement was found to be highly efficient
at room temperature using 25 mol % quantities of
Cu(BF4)2ÆnH2O in a variety of solvents, although dry
dichloromethane was the solvent of choice due to the
short reaction times observed. The rearrangement of sty-
rene oxide proceeded readily to give phenylacetaldehyde
contaminated with small quantities of the suspected
aldol product. This transformation is particularly note-
worthy given the sensitivity of phenylacetaldehyde to
acidic conditions and the difficulties encountered in pre-
viously reported procedures,4d and clearly demonstrates
O
R1
R2
R3
R1
R2
R3
O
R1
R2
H
H
R3
H
Scheme 1.
Keywords: Copper tetrafluoroborate; Lewis acid catalyst; Meinwald
rearrangement.
*
Corresponding author. Fax: +44
A.E.Graham@swansea.ac.uk
0
1792 295747; e-mail:
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.055

5920
M. W. C. Robinson et al. / Tetrahedron Letters 47 (2006) 5919–5921
Table 1. Rearrangements of epoxides catalyzed by Cu(BF4)2ÆnH2O
Entry
1
Epoxidea
Time
Productb
Yieldc (%)
90
H
H
O
O
20 min
O
28a
60 min
90 min
85
O
O
H
O
38b
95d
O
H
48c
15 min
5 h
90
89
O
O
O
58d
88e
O
6
20 min
CHO
a All epoxides were used as supplied or were synthesized using published procedures (see Ref. 8).
b All reactions were carried out at room temperature in dichloromethane using 25 mol % of catalyst.
c All products gave satisfactory spectroscopic data.
d Carried out at reflux.
e >95% regioselectivity as determined by GC–MS analysis of the crude reaction mixture.
the benign nature of this catalyst. Similarly, a-methylsty-
rene oxide underwent efficient rearrangement to produce
2-phenylpropionaldehyde in high yield. The rearrange-
ment of stilbene oxides has been used to demonstrate reg-
ioselectivity, since rearrangement can occur with either
phenyl migration to produce diphenylacetaldehyde or
with hydrogen migration to give deoxybenzoin. Under
our conditions trans-stilbene oxide underwent regioselec-
tive rearrangement to produce diphenylacetaldehyde
Typical procedure: a-Methylstyrene oxide (127 mg,
0.95 mmol) was dissolved in dry dichloromethane
(10 ml) at room temperature. Copper tetrafluoroborate
(59.3 mg, 0.25 mmol) was added and the reaction was
stirred at room temperature and monitored by TLC.
Upon completion, the reaction mixture was diluted
with dichloromethane (30 ml) and washed with water
(4 · 40 ml). The organic phase was dried over magnesium
sulfate and the solvent removed to give an oil that was
purified by chromatography (petrol ! 10% ethyl ace-
tate:petrol) to give 2-phenylpropionaldehyde (108 mg,
1
in excellent yield as the only product observed by H
NMR spectroscopy of the crude reaction mixture. Disap-
pointingly, the rearrangement of cyclohexene oxide pro-
vided only trace amounts of cyclohexanone even after
prolonged heating in chloroform, although the starting
material was recovered unchanged in contrast to the
previous reports where halohydrins are produced.4b
However, dihydronaphthalene oxide did produce the
expected tetralone in high yield on exposure to extended
reaction times. The rearrangement of a-pinene oxide with
this catalyst is particularly noteworthy given the number
of potential products that can be formed during the rear-
rangement process. We were therefore gratified to ob-
serve that this substrate underwent a highly selective
rearrangement to give campholenic aldehyde as the ma-
jor product with ꢀ95% selectivity by GC–MS in addition
to small quantities of isomeric products.7
1
85%) as a colourless oil; H NMR (CDCl3; 400 MHz)
d = 9.62 (1H, d, J = 1.5 Hz), 7.40–7.20 (5H, m), 3.55
(1H, dq, J = 7 and 1.5 Hz), 1.45 (3H, d, J = 7 Hz); 13C
NMR (CDCl3; 100 MHz) d = 201.9, 137.7, 129.0, 128.5,
128.1, 52.9, 14.6; MS (EI) m/z 134, (M)+; mmax (film)/
cmꢁ1 (neat) 2978, 1718, 1494, 1452, 1020, 759 and 697.
Acknowledgements
The authors would like to thank the Engineering and
Physical Sciences Research Council for funding
(MWCR) and the EPSRC National Mass Spectrometry
Service, University of Wales Swansea, UK.
In conclusion, we have demonstrated that copper tetra-
fluoroborate is a highly efficient and effective reagent
which catalyzes the Meinwald rearrangement of a range
of epoxides to carbonyl compounds under mild reaction
conditions. The benign nature of the catalyst in addition
to its low cost and ease of use offers an attractive alter-
native to established methodologies.
References and notes
1. Meinwald, J.; Labana, S. S.; Chadha, M. S. J. Am. Chem.
Soc. 1963, 85, 582–585.
2. Rickborn, B. In Comprehensive Organic Synthesis; Trost, B.
M., Ed.; Pergamon: Oxford, 1991; Vol. 3, Chapter 3.3. pp
733–775.

M. W. C. Robinson et al. / Tetrahedron Letters 47 (2006) 5919–5921
5921
3. (a) House, H. O. J. Am. Chem. Soc. 1955, 77, 3070–3075;
(b) Rickborn, B.; Gerkin, R. M. J. Am. Chem. Soc. 1971,
93, 1693–1700; (c) Maruoka, K.; Takashi, O.; Yamamoto,
H. Tetrahedron 1992, 48, 3303–3312.
4. (a) Kulasegaram, S.; Kulawiec, R. J. J. Org. Chem. 1997,
62, 6547–6561; (b) Ranu, B. C.; Jana, U. J. Org. Chem.
5. Lee, S. H.; Lee, J. C.; Li, M. X.; Kim, N. S. Bull. Korean
Chem. Soc. 2005, 26, 221–222.
6. An epoxide has been identified as an intermediate in the
rearrangement of an a-hydroxy thioacetal to an aldehyde
catalyzed by copper(I) triflate; Cohen, T.; Kuhn, D.; Falck,
J. R. J. Am. Chem. Soc. 1975, 97, 4749–4751.
´
1998, 63, 8212–8216; (c) Karame, I.; Tommasino, M. L.;
7. Motherwell, W. B.; Bingham, M. J.; Pothier, J.; Six, Y.
Tetrahedron 2004, 60, 3231–3241.
Lemaire, M. Tetrahedron Lett. 2003, 44, 7670–7687; (d)
Anderson, A. M.; Blazek, J. M.; Garg, P.; Payne, B. J.;
Mohan, R. S. Tetrahedron Lett. 2000, 41, 1527–1530; (e)
Bhatia, K. A.; Eash, K. J.; Leonard, N. M.; Oswald, M. C.;
Mohan, R. S. Tetrahedron Lett. 2001, 42, 8129–8132; (f)
Deng, X.-M.; Sun, X.-L.; Tang, Y. J. Org. Chem. 2005, 70,
6537–6540.
8. (a) Gajewski, J. J.; Gee, K. R.; Jurayj, J. J. Org. Chem.
1990, 55, 1813–1822; (b) Tanner, D.; Birgersson, C.;
Gogoll, A.; Luthman, K. Tetrahedron 1994, 50, 9797–
9824; (c) Lowden, C. T.; Mendoza, J. S. Tetrahedron Lett.
2002, 43, 979–982; (d) Becker, A. R.; Janusz, J. M.; Bruice,
T. C. J. Am. Chem. Soc. 1979, 101, 5679–5687.