Highly selective methanesulfonic acid-catalyzed 1,3-isomerization of allylic alcohols

Article abstract of DOI:10.1016/j.tetlet.2007.09.156

Secondary and tertiary allylic alcohols undergo 1,3-isomerization smoothly in the presence of methanesulfonic acid under simple and efficient conditions to afford selectively the corresponding primary E-allylic alcohols in excellent yields.

Full text of DOI:10.1016/j.tetlet.2007.09.156

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Tetrahedron Letters 48 (2007) 8505–8507
Highly selective methanesulfonic acid-catalyzed
1
,3-isomerization of allylic alcohols
*
Rajender Reddy Leleti, Bin Hu, Mahavir Prashad and Oljan Repicˇ
Process R&D, Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza,
East Hanover, NJ 07936, USA
Received 24 May 2007; revised 25 September 2007; accepted 26 September 2007
Available online 29 September 2007
Abstract—Secondary and tertiary allylic alcohols undergo 1,3-isomerization smoothly in the presence of methanesulfonic acid under
simple and efficient conditions to afford selectively the corresponding primary E-allylic alcohols in excellent yields.
ꢀ
2007 Elsevier Ltd. All rights reserved.
Allylic alcohols and their derivatives are important pre-
cursors in various synthetic organic reactions.1 The
direct 1,3-allylic rearrangement of allylic alcohols is a
useful reaction, because one regioisomer is often more
difficult to prepare than the other, but has received little
attention. Only a few methods have been reported in the
methanesulfonic acid in 1,3-isomerization of allylic
alcohols.
The treatment of a-vinyl benzyl alcohol 1 with methane-
sulfonic acid at room temperature over 12 h underwent
1,3-isomerization to afford the corresponding E-selective
2
5
literature for this transformation, such as H SO ,
cinnamyl alcohol 2 in 91% yield. Encouraged by these
2
4
3
CoCl2 and isomerization catalyzed by transition-metal
oxo complexes. These methods suffer from low yields
results, we turned our attention to substituted a-vinyl
benzyl alcohols. Interestingly, a large number of
substituted a-vinyl benzyl alcohols such as p-chloro-,
p-bromo-, o-bromo-, p-fluoro-, o-fluoro-, p-nitro-,
p-methoxy, and o-methoxy derivatives isomerized
efficiently in the presence of methanesulfonic acid to
afford corresponding E-selective substituted cinnamyl
alcohols in high yields (Table 1, entries a–i). This method
is equally effective for electron-rich as well as electron-
deficient aromatic allylic alcohols.
4
and low regioselectivity. In addition, transition-metal
oxo complexes are moisture-sensitive and highly expen-
sive reagents. To overcome these problems, herein we
report a new, simple, and efficient protocol for this
transformation using inexpensive methanesulfonic acid
(
Scheme 1).
As a part of our continuing interest in the development
of new synthetic methodologies, we disclose our results
on the methanesulfonic acid-catalyzed E-selective 1,3-
isomerization of allylic alcohols. To the best of our
knowledge, there have been no reports on the use of
We also investigated a number of aliphatic allylic alco-
hols and tertiary allylic alcohols (Table 1, entries j–o)
in the presence of methanesulfonic acid to selectively
afford the corresponding primary E-allylic alcohols in
1
OH
MeSO H, THF / H O (4 :1)
rt, 12 h, 74-92%
good yields. The products were characterized by
H
3
2
1
3
NMR, C NMR, and mass spectroscopic data and also
R
OH
4
a,b,6
R
by comparison with authentic samples.
In all cases,
2
the reactions proceeded efficiently in high yields at ambi-
1
ent temperature. As a solvent, THF/H O (4:1) appeared
2
Scheme 1.
to give the best results. Of the various acids investigated
(
Table 2), methanesulfonic acid gave the best results in
terms of conversion and reaction rates. The reaction
did not go to completion with triflic acid or p-toluene-
sulfonic acid, giving low yields. No reaction was
observed with acetic acid or trifluoroacetic acid.
Keywords: Methanesulfonic acid; Allylic alcohols; 1,3-Isomerization;
THF; Water.
*
Corresponding author. Tel.: +1 862 778 1291; fax: +1 973 781
188; e-mail: Rajender.leleti@novartis.com
2
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.156

8506
R. R. Leleti et al. / Tetrahedron Letters 48 (2007) 8505–8507
Table 1. 1,3-Isomerization of allylic alcohols via methanesulfonic acid catalysis
a
b
Entry
a
Substrate
OH
Product
Yield (%)
OH
OH
90
89
92
OH
b
c
OMe
OMe
OH
OH
MeO
MeO
OH
F
OH
d
e
82
86
F
OH
OH
F
F
OH
Br
OH
f
82
88
Br
OH
OH
g
Br
Br
OH
OH
h
i
O
+
N
86
91
O
+
N
O
O
OH
OH
Cl
Cl
OH
Me
Me
j
78
76
OH
Me
OH
k
OH
Me
OH
OH
OH
Me
Me
Me
Me
Me
Me
l
90
83
OH
OH
OH
m
Me
Me
Me
Me
n
o
82
74
Me
OH
Me
Me
Me
Me
Me
OH
a
1
13
All products were characterized by H NMR, C NMR and mass spectroscopy.
Isolated yields.
b

R. R. Leleti et al. / Tetrahedron Letters 48 (2007) 8505–8507
8507
Table 2. 1,3-Isomerization of allylic alcohols in the presence of
different acids
conversion of secondary and tertiary allylic alcohols to
primary allylic alcohols in excellent yields.
OH
Acid, THF / H O (4 : 1)
2
OH
rt, 12 h
References and notes
a
1. (a) Wipf, P. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol.
5, pp 827–873; (b) Hill, R. K. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
Oxford, 1991; Vol. 5, pp 785–826; (c) Katsuki, T. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999;
Vol. 2, pp 621–648; (d) Charette, A. B.; Marcoux, J.-F.
Synlett 1995, 1197–1207; (e) Uma, R.; Cr e´ visy, C.; Gr e´ e, R.
Chem. Rev. 2003, 103, 27–51; (f) Marshall, J. A. Chem. Rev.
Entry
Acid
Yield (%) (recovered SM (%))
1
2
3
4
5
6
MeSO
TfOH
3
H
91 (0)
65 (5)
65 (20)
62 (21)
0 (90)
0 (85)
PhSO
p-CH
CH COOH
CF COOH
3
H
3
C
6
H
4
SO
3
H
3
3
a
Isolated yields.
2
000, 100, 3163–3185.
2
3
4
. Yoshihito, A.; Akio, O.; Hiroshi, I. Chem. Pharm. Bull.
1982, 30, 881–886.
. Mukhopadhyay, M.; Reddy, M. M.; Maikap, G. C.; Iqbal,
J. J. Org. Chem. 1995, 60, 2670–2676.
+
OH
OH2
+
H
. (a) Morrill, C.; Grubbs, R. H. J. Am. Chem. Soc. 2005, 127,
2
842–2843; (b) Morrill, C.; Beutner, G.; Grubbs, R. H. J.
Org. Chem. 2006, 71, 7813–7825; (c) Ge, W.; Ampa, J.;
Rudy, L. L. Inorg. Chem. Acta 2005, 358, 933–940; (d)
Frank, R. F.; Rudy, L. L.; Ge, W. Inorg. Chem. Commun.
-
H O
2
2
002, 5, 384–387; (e) Schoop, T.; Roesky, H. W.; Nolter-
meyer, M.; Schmidt, H.-G. Organometallics 1993, 12, 571–
74; (f) Jacob, J.; Espenson, J. H.; Jensen, J. H.; Gordon,
+
OH2
5
M. S. Organometallics 1998, 17, 1835–1840.
5
. Typical experimental procedure: To a solution of alcohol
(
(
1.0 mmol) in THF/H
2.0 mmol) was added dropwise over 5 min at rt, and
2
O (4:1, 5 mL) methanesulfonic acid
+
H O
2
stirring was continued at this temperature for 12 h. The
progress of the reaction was monitored by TLC. After
complete conversion, the reaction mixture was quenched
with saturated NaHCO3 solution (10 mL). The resulting
mixture was extracted with i-PrOAc (3· 10 mL). The
combined organic layers were washed with water and
concentrated under reduced pressure. The resulting crude
product was purified by column chromatography (silica gel
+
OH
-
H+
OH2
2
Scheme 2.
2
30–400 mesh) using a gradient mixture of i-PrOAc and
pentane to furnish pure allylic alcohol.
A possible mechanism for this reaction is depicted in
Scheme 2.
6
. (a) Thomas, D. A.; Daniela, C.; Julia, A. C.; Dennis, K. T.;
Edward, R. T. J. Org. Chem. 2005, 70, 8344–8351; (b) Ryo,
T.; Naoki, U.; Kasuke, T.; Kengo, Y.; Narihito, S. J. Am.
Chem. Soc. 2001, 123, 9525–9534; (c) Milton, L. H.;
Robert, A. Z.; Micheal, N. C.; Norman, P. J.; John, M.;
Kathryn, T.; David, A. B.; Ihor, E. K.; Karen, M. H. J.
Med. Chem. 1990, 33, 908–918.
In conclusion, we have developed a simple and efficient
approach for 1,3-isomerization of allylic alcohols using
inexpensive methanesulfonic acid as the catalyst. The
notable feature of this reaction is a high regioselective