DABCO-catalyzed formation of 4-methoxy-1,3-dioxolan-2-ones and their synthetic applications in the aromatic electrophilic substitution

Article abstract of DOI:10.1016/j.tetlet.2008.09.173

DABCO is a very effective catalyst in the formation of 4-methoxy-1,3-dioxolan-2-ones 10 from the corresponding α-carbonatoaldehydes 8 intermediates. The Friedel-Crafts reaction pathway of the cyclic carbonate 10 is dependent on the electron density of the

Full text of DOI:10.1016/j.tetlet.2008.09.173

Tetrahedron Letters 50 (2009) 748–751
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
DABCO-catalyzed formation of 4-methoxy-1,3-dioxolan-2-ones and their
synthetic applications in the aromatic electrophilic substitution
*
Yung-Son Hon , Chen-Yi Kao
Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi, Taiwan 62102, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
DABCO is a very effective catalyst in the formation of 4-methoxy-1,3-dioxolan-2-ones 10 from the corre-
Received 13 August 2008
Revised 30 August 2008
Accepted 2 September 2008
Available online 3 December 2008
sponding
a-carbonatoaldehydes 8 intermediates. The Friedel–Crafts reaction pathway of the cyclic car-
bonate 10 is dependent on the electron density of the aromatic nucleophiles.
Ó 2008 Elsevier Ltd. All rights reserved.
This Letter is dedicated to Professor Chun-
Chen Liao for his inspiration and on the
occasion of his retirement
Keywords:
Ene-diol rearrangement
4-Methoxy-1,3-dioxolan-2-ones
Benzofurans
DABCO
We have reported that the ozonolysis of 1-substituted allyl
silyl ethers or 1-substituted allyl carboxylates 1 followed by
The synthesis and use of cyclic alkylene carbonates in industrial
applications have been fully realized.2 However, to the best of our
knowledge, both the synthesis and the synthetic application of the
treatment with bases gave the corresponding
acyloxy-ketones 3 in good yields. It is proposed to proceed via a
novel ene-diol rearrangement of the corresponding -silyloxy-
or
-acyloxyaldehydes intermediates 2 (Scheme 1).1 When R is
a-silyloxy- or a-
a
-methoxy cyclic carbonate 10 are undisclosed in the literature.3
a
Therefore, we are interested in improving the preparation of cyclic
a
carbonate 10a from -carbonatoaldehyde 8a. Herein, we want to
a
an aryl group in compound 2, Et3N is an effective base to promote
the rearrangement. Stronger base such as DBU (1,8-diazabicy-
clo[5.4.0]undec-7-ene) is needed when R of compound 2 is an al-
kyl group.
report our findings that DABCO (1,4-diazabicyclo[2.2.2]octane) is
an excellent catalyst in the cyclic carbonates formation, and these
cyclic carbonates are demonstrated to be useful in organic
synthesis.
When methyl 1-phenylallyl carbonate (4) was sequentially
treated with O3 and Et3N, the rearranged product 6 was isolated
in 74% yield as expected (Eq. 1). To our surprise, no rearranged
product 9a was observed when 1-cyclohexylallyl methyl carbonate
(7a) was sequentially treated with O3 and DBU. The crude product
1H NMR spectrum indicates that aldehyde 8a was formed instead.
To our surprise, we found that aldehyde 8a was rearranged to
cyclic carbonate 10a after silica gel column chromatography, albeit
in low yield (Eq. 2). It indicates that methoxycarbonyl is a migra-
OCO2Me
O
CO2Me
O
1. O3, CH2Cl2,
-78 oC;
2. 1.1 equiv.
Et3N
OCO2Me
ð1Þ
Ph
CHO
Ph
Ph
74%
4
5
6
not observed
1. O3, CH2Cl2, -78 oC
2. 1.1 equiv. Base
Σ
O
Σ
O
O
tory group when
a-aryl-aldehyde 5 is treated with base. On the
base = Et3N if R = Aryl
base = DBU if R = Alkyl
R
R
1
3
other hand, -cyclohexyl-aldehyde 7a prefers the cyclic carbonate
a
Σ =
formation to the ene-diol rearrangement.
Σ
O
trialkylsilyl,
acyl
ene-diol
rearrangement
R
CHO
2
* Corresponding author. Tel.: +886 5 2720411x66412; fax: +886 5 2721040.
E-mail address: cheysh@ccu.edu.tw (Y.-S. Hon).
Scheme 1. Synthesis of
diate 2.
a-silyloxy- or a-acyloxy-ketones 3 via aldehyde interme-
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.173

Y.-S. Hon, C.-Y. Kao / Tetrahedron Letters 50 (2009) 748–751
749
1. O3, CH2Cl2,
-78 oC;
2. 1.1 equiv.
DBU
OCO2Me
surface of alumina
O
CO2Me
O
promoted
by
alumina
OCO2Me
O
O
favored
OMe
O
Cy
CHO
Cy
O
7a
OMe or MeOH
Cy
O
7a
8a
9a
O
H
H
Cy
disfavored
not observed
silica gel
Cy
OMe or MeOH
ð2Þ
A
B
O
(shielded by solid support)
N
N
O
O
DABCO =
10a-syn (major) + 10a-anti (minor)
Cy
MeOH
O
OMe
10a
O
MeO
O
O
O
O
OMe
O
O
O
H
Cy
H
Cy
H
OMe
O
Cy
H
DABCO
H
DABCO
DABCO
H
a or
a, b
OCO2Me
OCO2Me
O
O
C
D
E
c or d
R
CHO
R
Figure 1. The plausible mechanism of the carbonate 10a formation from 7a
R
OMe
7a-7e
8a-8e
promoted by either alumina or DABCO.
10a-10e
(syn & anti)
R = Cyclohexyl 7a
PhCH2CH2- 7b
PhCH2- 7c
solid catalyst: silica gel; alumina
organocatalyst: DABCO, DMAP, etc.
t-Butyl 7d
mina is increased from 5 to 10 (entries 2 and 3). The basic alumina
is the best catalyst among three types of alumina (entries 3–5).
When methanol was used as the solvent in the presence of basic
alumina, the reaction time is shorter and the yield is improved to
47% (entries 2 and 6). The alumina is not required if DMAP is used
as catalyst (entries 7 and 8). The removal of Ph3PO is not required if
DMAP is used as catalyst, and the yield is increased (entries 7, 8,
and 10; i.e., Procedure B condition). DABCO is a better catalyst than
DMAP to promote the cyclization (entries 8 and 9; 10 and 11).
Longer reaction time is needed if the mol equivalent of the DABCO
is decreased from 0.1 to 0.05 (entries 12 and 13). The reaction is
complete by heating at 50 °C for 5 h when 0.05 mol equiv of the
DABCO is used. However, the yield is reduced to 71% (entries 13
and 14). The acidic catalysts, such as PTSA and PPTS, are inferior
to the nucleophilic base catalysts in this study (entries 15, 16,
and 12). The DABCO-catalyzed cyclization is also applicable to
those substrates with phenylethyl, benzyl, tert-butyl, and 3-ben-
yzloxypropyl substituents (entries 17–20). In general, the syn-iso-
BnO(CH2)3- 7e
Scheme 2. Reagents and conditions: (a) (i) O3, CH2Cl2, ꢀ78 °C; (ii) 0.8 equiv Ph3P;
(b) removed Ph3PO by filtration; (c) solid catalyst and/or organocatalyst in CH2Cl2;
(d) solid catalyst and/or organocatalyst in MeOH/CH2Cl2.
The aldehyde 8a was prepared from the ozonolysis of alkene 7a
followed by reduction with Ph3P. The crude product was triturated
with n-hexane under sonication, the Ph3PO was filtered and the fil-
trate was concentrated to give the crude 8a (i.e., Procedure A con-
dition). The crude residue was mixed with either silica gel or
alumina (5–10 wt equiv) in the solvent as indicated in Table 1,
and the slurry was stirred at room temperature until the disap-
pearance of the aldehyde 8a. The result is shown in Table 1. In
CH2Cl2, basic alumina is a better catalyst than silica gel to promote
the cyclization of aldehyde 8a (Scheme 2; Table 1, entries 1 and 2).
The reaction time is shorter when the weight equivalent of the alu-
Table 1
The cyclic carbonate 10 formation from allyl carbonate 7 via aldehyde 8 under various catalytic conditions
Entry
Starting material R =
Procedurea
Solid support (wt equiv)
Catalyst (equiv)
Solventb
Time (h)
Yield (%) (syn:anti)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Cyclohexyl 7a
Ph(CH2)2-7b
PhCH2-7c
A
A
A
A
A
A
A
A
A
B
B
B
B
B
B
B
B
B
B
B
SiO2 (10)
Basic Al2O3 (5)
Basic Al2O3 (10)
Acidic Al2O3 (10)
Neutral Al2O3 (10)
Basic Al2O3 (10)
Basic Al2O3 (10)
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
48
28
6
6
6
6
6
6
6
8
6
8
20
5
12
12
8
8
8
10a —c (1:0)
10a 29 (8.3:1)
10a 32 (8.3:1)
10a 29 (6:1)
10a 23 (6:1)
10a 47 (6:1)
10a 59 (5.9:1)
10a 60 (6.2:1)
10a 70 (6.5:1)
10a 71 (5.8:1)
10a 91 (5.6:1)
10a 91 (6.3:1)
10a 87 (6.3:1)
10a 71d (6.2:1)
10a 0e
DMAP (0.2)
DMAP (0.2)
DABCO (0.2)
DMAP (0.2)
DABCO (0.2)
DABCO (0.1)
DABCO (0.05)
DABCO (0.05)
PPTS (0.2)
PTSA (0.2)
DABCO (0.1)
DABCO (0.1)
DABCO (0.1)
DABCO (0.1)
10a 34f (2.4:1)
10b 93 (2.5:1)
10c 83 (2.9:1)
10d 76 (1:0)
10e 84 (3.5:1)
t-Butyl 7d
BnO(CH2)3-7e
10
a
To carry out the cyclization after removal of Ph3PO is termed as Procedure A condition. To carry out the cyclization in the presence of Ph3PO is termed as Procedure B
condition.
b
c
d
e
f
Anhydrous solvent.
10% conversion and 10a:8a = 1:8 by 1H NMR integration.
Reaction temperature is 50 °C.
Recovered aldehyde 8a.
60% conversion.

750
Y.-S. Hon, C.-Y. Kao / Tetrahedron Letters 50 (2009) 748–751
MeO
MeO
[Ti]O
OMe
TiCl4
[Ti]O
Cy
1,3-dimethoxy-
benzene
OMe
1,3-dimethoxy-
benzene
[Ti]O
TiCl4
10a
11a
Friedel-Crafts
Reaction
OMe
Cy
H
Cy
H
Friedel-Crafts
Reaction
10a-B
CO2
10a-C
OMe
10a-A
1,3,5-trimethoxybenzene
Friedel-Crafts Reaction
MeO
MeO
[Ti]O
OMe
TiCl4
OMe
MeO
[Ti]O
Cy
OMe
[Ti]O
Cy
-H+
workup
Cy
H
15a
H
OMe OMe
10a-B'
OMe
OMe
10a-D'
10a-C'
Figure 2. The plausible mechanisms for the formation of compounds 11a and 15a from cyclic carbonate 10a via Friedel–Crafts reaction.
13a and 13b in good yield (Scheme 3). Presumably, the carbonyl
group-directed demethylation of compound 12a at ortho-position
selectively (i.e., via intermediate 12a-A) occurred before the ben-
zofuran ring formation. When the demethylation reaction was car-
ried out with 3 equiv of BBr3 in CH2Cl2, the benzofuran 14a was
formed in 58% yield. It is interesting to point out that BBr3 in EtOAc
is less reactive and more selective in the demethylation of com-
pound 12a in comparison with the reaction in CH2Cl2.
Cy
O
O
OH
i
ii
iii
MeO
Ar
10a
Ar
Cy
12a
63%
Cy
11a
or iv
Ar
Ar
Ar = 2,4-dimethoxyphenyl
OR
R = Me 13a 53%
and R = H 13b 18%
OMe
Scheme 3. Reagents and conditions: (i) 2.0 equiv TiCl4, 2.2 equiv 1,3-dimethoxy-
benzene, CH2Cl2, ꢀ50 °C to rt; (ii) 1.5 equiv Dess–Martin periodinane; (iii) 1 equiv
BBr3, EtOAc, 0 °C to rt, 12 h; (iv) 3 equiv BBr3, EtOAc, 0 °C to rt, 4 h.
Br
Br
Br
Cy
Cy
O
O
B
HO
MeO
MeO
O
OMe
O
OMe
ii
O
Me
i
10a
83%
OH
O
80%
14a
Cy
12a-A
Cy
Br2B
OMe
OMe
16a
15a
OH
OMe
Scheme 4. Reagents and conditions: (i) 2.0 equiv TiCl4, 1.5 equiv 1,3,5-trimethoxy-
benzene, CH2Cl2, ꢀ50 °C to rt; (ii) 1 equiv BBr3, EtOAc, 0 °C, 12 h.
Under similar condition, the cyclic carbonate 10a reacted with
1,3,5-trimethoxybenzene in the presence of TiCl4 at ꢀ50 °C in
CH2Cl2 to give mono-arylated ketone 15a in 83% yield, and no
diarylated product was observed (Scheme 4). Ketone 15a was then
treated with BBr3 in ethyl acetate to give the benzofuran 16a in
80% yield. The carbonyl group-directed demethylation of com-
pound 15a at the ortho-position selectively occurred before the
benzofuran ring formation.
The rationale for formation of compounds 11a and 15a from cyc-
lic carbonate 10a was described in Figure 2. The cyclic carbonate
10a was decomposed by the first equivalent of TiCl4 to give oxo-
nium intermediate 10a-A. When 1,3-dimethoxybenzene was used
as nucleophile, 10a-A undergoes Friedel–Crafts reaction to give
intermediate 10a-B. The benzylic methoxy group of 10a-B is re-
moved by the help of the second equivalent of TiCl4 to give the
intermediate 10a-C. It then undergoes the second Friedel–Crafts
reaction to give the diarylated product 11a. Interestingly, when
the more electron-rich nucleophile such as 1,3,5-trimethoxyben-
zene was used as nucleophile in the reaction, its reaction pathway
is different from that of using 1,3-dimethoxybenzene. The interme-
diate 10a-C0 undergoes deprotonation instead of second arylation
to give mono-arylated product 15a. In conclusion, DABCO is a very
efficient organocatalyst in the formation of 4-methoxy-1,3-dioxo-
mer is formed preferentially in each case (Table 1). Their syn- and
anti-stereochemistry are confirmed by their 2D-NOESY technique.
The rationale of the stereoselectivity of the ring formation is de-
scribed as follows. The basic alumina promotes the cyclization of
compound 8a to give intermediate A which undergoes elimination
to give oxonium ion B, where the cyclohexyl group is oriented in
the opposite side of the alumina surface due to the steric hin-
drance. Either methoxide or methanol will attack the oxonium
ion B from the less hindered b-face preferentially to give 10a-syn
predominately as shown in Figure 1. DABCO is known to be the
effective catalyst in Morita–Baylis–Hillman reaction.4 In the pres-
ent reaction, the nucleophilic attack of aldehyde 7a by DABCO fol-
lowed by elimination to give the intermediate E. Nucleophilic
substitution of intermediate E with methanol gives 10a-syn as
the major product (Fig. 1). Interestingly, the formation of 4-alkyl-
1,3-dioxol-2-one via a proton elimination is not observed.
A mixture of cyclic carbonate 10a and 2.2 equiv of 1,3-dime-
thoxybenzene in CH2Cl2 was treated with 2.0 equiv of TiCl4 at
ꢀ50 °C to give the diarylated product 11a in 63% yield (Scheme
4). Presumably, the Friedel–Crafts reaction of 1,3-dimethoxyben-
zene with intermediate 10a-A gave the intermediate 10a-B. The
leaving of the benzylic methoxy group was promoted by TiCl4 to
give intermediate 10a-C, which then underwent the second
Friedel–Crafts reaction with 1,3-dimethoxybenzene to give diaryl
compound 11a (Fig. 2). Alcohol 11a was oxidized with Dess–
Martin periodinane to give ketone 12a, which was then treated
with BBr3 (1 or 3 equiv) in ethyl acetate to give the benzofuran
lan-2-ones 10 from the corresponding
a-carbonatoaldehydes 8.
The cyclic carbonate 10 reacts with TiCl4 to give the intermediate
10a-A. This intermediate reacts with 1,3-dimethoxybenzene to
give the b,b-diaryl ethanol 11a. The cyclic carbonate 10 is consid-
ered to be the synthetic equivalent of the synthon-I (Fig. 3). When
1,3,5-trimethoxybenzene was used as the nucleophile, the
a-ary-
lated ketone 15a was formed. The cyclic carbonate 10 is considered

Y.-S. Hon, C.-Y. Kao / Tetrahedron Letters 50 (2009) 748–751
751
Supplementary data
OH
O
Synthon-I
O
when reacting with moderately
electron-rich aromatic compounds.
R
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.09.173.
O
O
Synthon-II
when reacting with highly
electron-rich aromatic compounds.
R
OMe
R
References and notes
1. (a) Hon, Y. S.; Wong, Y. C. Tetrahedron Lett. 2005, 46, 1365–1368; (b) Hon, Y. S.;
Wong, Y. C.; Wu, K. J. J. Chin. Chem. Soc. 2008, 55, 896–914.
2. Clements, J. H. Ind. Eng. Chem. Res. 2003, 42, 663–674.
Figure 3. 4-Methoxy-1,3-dioxolan-2-ones can be considered as either Synthon I or
II depending on the nucleophiles.
3. Hosoda, K.; Kunieda, T.; Takizawa, T. Chem. Pharm. Bull. 1976, 24, 2927–2933.
4. Some selected review of Baylis–Hillman reaction: (a) Basavaiah, D.; Rao, K. V.;
Reddy, R. J. Chem. Soc. Rev. 2007, 36, 1581–1588; (b) Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (c) Ciganek, E. Org. React.
1997, 51, 201–350; (d) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996,
52, 8001–8062; (e) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653–4670.
5. (a) Liao, X.; Weng, Z.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 195–200. and
references cited therein; (b) Chen, G. S.; Kwong, F. Y.; Chan, H. O.; Yu, W. Y.;
Chan, A. S. C. Chem. Commun. 2006, 1413–1415; (c) Marion, N.; Ecarnot, E. C.;
Navarro, O.; Amoroso, D.; Bell, A.; Nolan, S. P. J. Org. Chem. 2006, 71, 3816–3821.
and references cited therein; (d) Aggarwal, V. K.; Olofsson, B. Angew. Chem., Int.
Ed. 2005, 44, 5516–5519; (e) Xie, X.; Cai, G.; Ma, D. Org. Lett. 2005, 7, 4693–4695;
(f) Fraboni, A.; Fagnoni, M.; Albini, A. J. Org. Chem. 2003, 68, 4886–4893; (g) Fox,
J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 1360–
1370; (h) Morgan, J.; Pinhey, J. T.; Rowe, B. A. J. Chem. Soc., Perkin Trans. 1 1997,
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to be the synthetic equivalent of the synthon-II (Fig. 3). The
lation of ketone is extensively studied in past decade.5 Most impor-
tantly, the reversed polarity disconnection of the -arylation in
a-ary-
a
this study is discovered in comparison with the approaches in
the literature.5
Further studies are in progress in order to investigate the fur-
ther synthetic applications of the cyclic carbonates 10 with differ-
ent nucleophiles in the presence of Lewis acids.
Acknowledgments
We are grateful to the National Science Council and National
Chung Cheng University for the financial support.