Silica gel-mediated rearrangement of allylic acetates. Application to the synthesis of 1,3-enynes

Article abstract of DOI:10.1039/c0cc00035c

Silica gel was found to efficiently promote the rearrangement of allylic acetates into their most stable regioisomers under microwave irradiation. The reaction is easy to perform and eco-friendly. This method was applied to the metal-free synthesis of 1,3-enynes.

Full text of DOI:10.1039/c0cc00035c

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Silica gel-mediated rearrangement of allylic acetates. Application to the
synthesis of 1,3-enynesw
´ ´
Anna Serra-Muns, Amandine Guerinot, Sebastien Reymond* and Janine Cossy*
Received 19th February 2010, Accepted 9th April 2010
First published as an Advance Article on the web 12th May 2010
DOI: 10.1039/c0cc00035c
Silica gel was found to efficiently promote the rearrangement of
allylic acetates into their most stable regioisomers under
microwave irradiation. The reaction is easy to perform and
eco-friendly. This method was applied to the metal-free synthesis
of 1,3-enynes.
Table 1 Optimisation of the allylic rearrangement conditionsa
Entry SiO2/5a t/h T/1C, mWb Solvent
t (%)c 6a, yield (%)d
Increasing attention has been paid recently to the atom-
economic 1,3-rearrangement of propargylic and allylic
acetates promoted by Pd(II)-, Au-, Cu-, Eu- or Hg-based metal
catalysts.1 Compared to Brønsted acid-mediated processes, the
use of metal complexes avoids side reactions such as elimina-
tion or skeletal rearrangement.2 However, in addition to the
cost of these metal complexes, expensive additives such as
phosphine or carbene ligands are often required to obtain
good yields of the rearranged products.1 Herein, we report
that the rearrangement of allylic acetates bearing a phenyl or a
propargyl substituent can be promoted by silica gel3 under
microwave irradiation.
1
2
3
4
5
6
1/1
2/1
2/1
2/1
2/1
4/1
20
20
20
20
1
50, —
80, —
120, —
120, —
120, mW
CH2Cl2
CH2Cl2
CH3NO2
(CH2)2Cl2 100
(CH2)2Cl2 80
(CH2)2Cl2 100
0
55
75
0
—
—
69
—
63
0.5 120, mW
100 mg mLÀ1
a
b
[5a]
=
.
mW = microwave-assisted heating.
c
d
t = conversion, determined by GC-MS. Isolated yield.
such as the silica gel/substrate weight ratio (1/1 to 4/1), the
solvent (CH2Cl2, (CH2)2Cl2, CH3NO2), the temperature (50 1C
to 120 1C) as well as the influence of microwave irradiation
(Table 1). The best yield in the rearranged product 6a was
obtained when the allylic acetate 5a was treated with a 2/1
weight ratio of silica gel at 120 1C in 1,2-dichloroethane. Under
these conditions, 6a was isolated in 69% yield after 20 h (Table 1,
entry 4). In addition, the use of microwave irradiation associated
to an increase of the amount of silica gel (4/1 silica/substrate
weight ratio) considerably shortened the reaction time as 6a was
obtained in 63% yield after 30 min (Table 1, entry 6).7
A silica gel-induced rearrangement of allylic acetate was first
observed during the preparation of the x-acetoxy allylic
acetate 3. Indeed, a cross-metathesis between 1 and 2 was
performed using Hoveyda–Grubbs catalyst, and after purification
on silica gel, a mixture of two products was obtained.4 The
expected cross-metathesis product was isolated in 31% yield
while the rearranged compound 4 was formed in 22% yield.
After investigations, silica gel was found to be responsible
for the rearrangement of 3 to the most stable conjugated
regioisomer 4 (Scheme 1).5,6
In order to extend the scope of this allylic rearrangement, a
variety of allylic acetates was heated under microwave irradiation
in the presence of silica gel in a 4/1 weight ratio.8 At first,
allylic esters 5b–5d, bearing electron-rich substituents on the
aromatic ring, were examined. These substrates reacted
smoothly as the corresponding regioisomers 6b–6d were
formed in excellent yields (6b = 98%, 6c = 86%, 6d = 92%)
after only 15 min at 80 1C (Table 2, entries 1–3).9
Following this preliminary result, the optimisation of the
conditions of the silica gel-promoted rearrangement of allylic
acetates was achieved on 5a. Several parameters were examined
On the other hand, acetates 5e and 5f, possessing an
electron-withdrawing group on the aromatic ring, did not
rearrange under the previously established conditions. To
overcome this low reactivity, silica gel was doped with 2%
of H2SO4 (silica S1) and 22% of H2SO4 (silica S2). Thanks to
the use of the acidified silica gel, linear acetates 6e and 6f
were obtained respectively in 54% and 71% yield (Table 2,
entries 4–5).10,11 However, even with acidified silica gel, no
reaction was observed with the pyridine derivative 5g (Table 2,
entry 6) probably due to the basicity of the pyridine nitrogen.
In order to study the influence of the substitution of the double
bond on the outcome of the rearrangement, allylic acetates
5h–5j, possessing a di- or a trisubstituted double bond, were
then examined. After 15 min at 80 1C, 6h was obtained in an
excellent yield of 94% (Table 2, entry 7). It is worth noting
Scheme 1
Laboratoire de Chimie Organique, ESPCI ParisTech, UMR CNRS
7084, 10, rue Vauquelin, 75231 Paris Cedex 05, France.
E-mail: sebastien.reymond@espci.fr, janine.cossy@espci.fr;
Fax: (+33)140794660; Tel: (+33)140794659
w Electronic supplementary information (ESI) available: Experimental
procedures, spectroscopic data and NMR spectra for compounds 5–8.
See DOI: 10.1039/c0cc00035c
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Table 2 Silica gel-induced rearrangementa
entry 8), however, a low chirality transfer was observed as an
enantiomeric excess of 10% was measured for 6i. Even in the case
of a trisubstituted double bond, the rearrangement proceeded
smoothly as 6j was obtained in 79% yield (Table 2, entry 9).
Interestingly, polyfunctional allylic acetates were successfully
rearranged as diacetates 5k and 5l were transformed in good
yields to 6k and 6l respectively (Table 3, entries 1–2). After two
consecutive migrations of the acetate group, 5m was trans-
formed to the dienic acetate 6m (65%) (Table 3, entry 3) and
6n was isolated in 78% yield from 5n (Table 3, entry 4).
This rearrangement was applied to the synthesis of
1,3-enyne units which are of considerable interest in organic
synthesis as they are present in natural products, pharma-
ceuticals and molecular materials for optics and electronics. Most
of the preparative methods involve metal-catalyzed reactions
such as the Sonogashira cross-coupling of alkynes with vinyl
halides.12 As the development of metal-free synthesis of these
moieties is highly desirable, the silica gel-mediated rearrangement
was applied to propargylic allylic acetates of type 7 which should
lead to the thermodynamically most stable isomers 8. The results
are summarized in Table 4. Ester 7a, which bears a tert-butyl
group substituent on the triple bond, was first examined and a
low yield in the corresponding 1,3-enyne 8a was obtained (23%)
(Table 4, entry 1). A dramatic influence of the substitution
pattern of the double bond was highlighted as acetate 7b, bearing
a terminal methyl group, furnished 8b in 63% yield (Table 4,
entry 2). The tert-butyl substituent on the alkyne could be
replaced by a linear alkyl chain without affecting the outcome
of the rearrangement (Table 4, entry 3) and the presence of a
phenyl substituent slightly improved the yield in the rearranged
product (Table 4, entry 4). A trimethylsilyl group as well as an
ester group are also tolerated (Table 4, entries 5–6). However, the
full conversion of 7e and 7f required harsher conditions (longer
reaction time/higher temperature and/or the use of acidified
silica) and moderate yields in the rearranged products were
observed. This strategy for the preparation of 1,3-enynes remains
attractive as, to the best of our knowledge, only one example of
1,3-allylic rearrangement has been reported to access these
1,3-enyne moieties.13
Silica
type/5
ratio
Yield
(%)b
Entry Substrate
Product
1
5b
5c
5d
6b
6c
6d
4/1
4/1c
4/1
98
86
92
2
3
4
5e
6e
6f
S1d 1/1 54
5
6
5f
S2d 1/1 71
5g
No reaction
4/1
—
7
8
5h
6h
4/1
94
82
79
5i,
(ee >
98%)
6i,
(ee = 4/1
10%)
9
5j
6j
4/1
a
b
c
Conditions: CH2Cl2, 15 min, 80 1C, mW. Isolated yield. 25 min.
S1: SiO2 doped with 2% H2SO4, S2: SiO2 doped with 22% H2SO4.
d
that the use of these conditions is compatible with the presence
of a tert-butyldimethylsilyl ether. The enantiomerically pure
allylic ester 5i was also rearranged to 6i in 82% yield (Table 2,
From a mechanistic point of view, this rearrangement
would proceed through a SN1 allylic pathway producing a
Table 3 Application to polyfunctional acetatesa
Entry
Substrate
Product
Silica type/5 ratio
Conditions
[B]
Yield (%)b
60c
1
5k
5l
6k
6l
4/1
2
3
4/1
4/1
[B]
[A]
74d
5m
5n
6m
6n
65
78
4
4/1
[B]
a
b
c
d
Conditions: [A]: CH2Cl2, 15 min, 80 1C, mW. [B]: (CH2)2Cl2, 30 min, 120 1C, mW. Isolated yield. syn/anti: 2.3/1. dr not determined.
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Table 4 Synthesis of 1,3-enynesa
method has been applied to propargylic allylic acetates
allowing a simple and metal-free access to 1,3-enyne moieties.
The CNRS (grant to AG) and the Commissionat per
a
Universitats I Recerca del Departament d’Innovacio
Universitats I Empresa de la Generalitat de Catalunya (grant
to ASM) are gratefully acknowledged.
Yield
(%)b
E/Z
Notes and references
Substrate
Product
ratio
Entry
1
t, T
1 Pd(II): (a) P. M. Henry, J. Chem. Soc. D, 1971, 328; (b) P. M. Henry,
J. Am. Chem. Soc., 1972, 94, 5200; (c) L. E. Overman and
F. M. Knoll, Tetrahedron Lett., 1979, 20, 321; (d) P. A. Grieco,
T. Takigawa, S. L. Bongers and H. Tanaka, J. Am. Chem. Soc., 1980,
102, 7587; (e) P. A. Grieco, P. A. Tuthill and H. L. Sham, J. Org.
Chem., 1981, 46, 5005; (f) Y. Tamaru, Y. Yamada, H. Ochiai,
E. Nakajo and Z. Yoshida, Tetrahedron Lett., 1984, 40, 1791;
(g) J. Clayden and S. Warren, J. Chem. Soc., Perkin Trans. 1, 1993,
2913; (h) S. Shekhar, B. Trantow, A. Leitner and J. F. Hartwig,
J. Am. Chem. Soc., 2006, 128, 11770. Other metal catalysts:
(i) L. E. Overman, C. B. Campbell and F. M. Knoll, J. Am. Chem.
Soc., 1978, 100, 4822; (j) M. Mukhopadhyay, M. M. Reddy,
G. C. Maikap and J. Iqbal, J. Org. Chem., 1995, 60, 2670;
(k) B. K. Shull and M. Koreeda, J. Am. Chem. Soc., 1996, 118,
11690; (l) W.-M. Dai, A. Wu, M. Y. H. Lee and K. W. Lai,
Tetrahedron Lett., 2001, 42, 4215; (m) P. Radha Krishna,
V. Kannan and G. V. M. Sharma, Synth. Commun., 2004, 34, 55;
(n) N. Marion, R. Gealageas and S. Nolan, Org. Lett., 2007, 9, 2653;
(o) C. Gourlaouen, N. Marion, S. Nolan and F. Maseras, Org. Lett.,
2009, 11, 81.
5 min, 23
80 1C
9/1
7a
7b
7c
8a
8b
8c
15 min,
80 1C
2
3
4
5
63
20 min,
80 1C
65
10 min, 71
80 1C
9/1
7d
7e
7f
8d
8e
8f
30 min, 45
120 1Cc
85/15
25 min, 51
80 1C,
SiO2 S1
84/16
2 See ref. 1c and i and references cited herein.
6
3 Silica gel Geduran Si60 (40–63 mm) was purchased from Merck.
4 The cross-metathesis reaction was quenched by addition of silica gel
followed by evaporation of the solvent under vacuum. Subsequent
silica gel column chromatography furnished a mixture of 3 and 4.
5 For a related rearrangement of cyclopropenyl acetates during silica
gel purification see: A. Masarwa, A. Stanger and I. Marek, Angew.
Chem., Int. Ed., 2007, 46, 8039.
6 For a review concerning the use of silica gel in organic synthesis,
see: A. K. Banerjee, M. S. Laya Mimo and W. J. Vera Vegas, Russ.
Chem. Rev., 2001, 70, 971.
7 When AcOH was used as the solvent in the absence of silica gel, 6a
was formed in 79% yield after 1 h at 120 1C under microwave
irradiation. However an aqueous basic work-up was necessary to
isolate 6a whereas a simple filtration was sufficient to remove the
silica gel. In addition, when 5j was heated for 15 min at 80 1C under
microwave irradiation in AcOH, incomplete conversion of 5j was
observed (5j/6j: 70/30), see Table 2, entry 9.
8 The nature of the solvent used (CH2Cl2 or (CH2)2Cl2) was deter-
mined according to the temperature required.
9 When 5b was submitted to microwave irradiation, for 15 min at
80 1C in the absence of silica gel, no conversion was observed.
10 See the experimental sectionw for details about the preparation of
modified silica gels S1 and S2.
11 When 5e was treated with 12 mol% of H2SO4 in CH2Cl2 at 80 1C
under microwave irradiation, no conversion was observed, proving
the crucial role of silica gel in the rearrangement.
12 R. Chinchilla and C. Najera, Chem. Rev., 2007, 107(3), 874;
K. C. Nicolaou, P. G. Bulger and D. Sarlah, Angew. Chem., Int.
Ed., 2005, 44, 4442.
a
Standard conditions: CH2Cl2, mW. b Isolated yield. c (CH2)2Cl2 was used.
carbocation intermediate which would remain non-dissociated
in the silica matrix.14 Indeed, the racemization observed
during the rearrangement of 5i to 6i indicates the formation
of a carbocation species, whereas an external nucleophile such
as water, acetylacetone or tosylamide is unable to trap this
intermediate. The mode of action of silica-gel to catalyze the
rearrangement remains unclear. A classical Brønsted acid
catalysis would be excluded.7,11 However, the addition of
H2O or Et3N to the reaction medium led to a dramatic
decrease in the conversion during the rearrangement of 5b to
6b.w These results could indicate a silica gel hydrogen-bonding
activation of the acetate carbonyl group.
In summary, the silica gel-mediated rearrangement of
secondary allylic acetates bearing propargylic or aromatic
substituents towards their most stable regioisomers has been
developed. The driving force of this process is the formation of
the most stable conjugated allylic acetates. The use of silica gel
as the promoter of the rearrangement makes the reaction easy
to perform, cheap and environmentally benign. The scope of
this reaction is broad as a wide array of allylic esters including
polyfunctional acetates has been rearranged successfully. This
13 A Eu(fod)3-catalyzed rearrangement was applied to propargylic
allylic methoxyacetates, see ref. 1f.
14 V. S. Joshi, N. P. Damodaran and S. Dev, Tetrahedron, 1971, 27, 475.
ꢀc
This journal is The Royal Society of Chemistry 2010
4180 | Chem. Commun., 2010, 46, 4178–4180