Diels - Alder reactions of silyl-substituted masked o-benzoquinones: Expedient access to alkenylsilanes

Article abstract of DOI:10.1055/s-2002-33503

A one-pot synthesis of several silyl bicyclic and oxatricyclic alkenes by inter- and intramolecular Diels--Alder reactions of 4-trimethylsilyl substituted masked o-benzoquinones derived from the corresponding 2-methoxyphenols is described.

Full text of DOI:10.1055/s-2002-33503

1520
LETTER
Diels–Alder Reactions of Silyl-Substituted Masked o-Benzoquinones:
Expedient Access to Alkenylsilanes
Diels–Alder
R
eac
h
tions of Sily
i
l-Subst
e
ituted
M
as
n
ked
o
-Benzo
-
quinonesHsun Lai, Po-Yin Lin, Rama Krishna Peddinti, Chun-Chen Liao*
Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan
E-mail: ccliao@mx.nthu.edu.tw
Received 21 June 2002
tates dimerization) and an electron-releasing group exerts
an opposite effect. A large group at C4 of MOB reduces
the propensity of dimerization. It occurred to us that the
introduction of a trimethylsilyl group at position-4 of the
parent MOB not only stabilizes these latent quinones, but
also provides an expedient route to the hitherto unknown
alkenylsilanes.
Abstract: A one-pot synthesis of several silyl bicyclic and oxatri-
cyclic alkenes by inter- and intramolecular Diels–Alder reactions of
4-trimethylsilyl substituted masked o-benzoquinones derived from
the corresponding 2-methoxyphenols is described.
Key words: 2-methoxyphenols, 4-silyl masked o-benzoquinones,
Diels–Alder reaction, silyl bicyclo[2.2.2]octenes, silyl oxatricy-
clo[4.3.1.0]decenes
The requisite 4-trimethylsilyl substituted 2-methoxyphe-
nols 2a–c were prepared in 87–95% yield from the corre-
sponding 4-bromo-2-methoxyphenols 1a–c via sequential
metal-halide exchange with BuLi at –78 °C and treatment
with TMSCl followed by quenching with 2 N HCl. We
initiated our studies utilizing 2-methoxy-4-trimethyl-sil-
ylphenol (2a). When 2a was subjected to oxidation with
diacetoxyiodobenzene (DAIB) in methanol in the pres-
ence of methyl vinyl ketone (MVK), the in situ generated
4-trimethylsilyl MOB 3a underwent the Diels–Alder re-
action with MVK to provide the cycloadduct 4a in high
yield.10,11 No trace of the dimer of MOB 3a was observed
from the 1H NMR spectrum of the crude reaction mixture.
Subsequently, the reactions of 2-methoxyphenol 2a with
methyl acrylate (MA) and methyl methacrylate (MMA) in
the presence of DAIB in methanol were carried out to pro-
duce the corresponding cycloadducts 5a and 6a in good
yields (Scheme 1, Table 1).
Alkenylsilanes constitute important building blocks for
olefin synthesis and serve as valuable synthons in organic
synthesis.1 Conventionally, vinylsilanes are prepared
from alkynes, carbonyl compounds and vinyl halides.
However, very few reports are available for the synthesis
of silyl bicyclic and tricyclic alkenes.2,3 In this Letter we
report a novel and convenient one-pot synthesis for the
preparation of various silyl bicyclo[2.2.2]octenes and
oxatricyclo[4.3.1.0]decenes from 4-trimethylsilyl substi-
tuted 2-methoxyphenols via the Diels–Alder cycloaddi-
tions of transiently generated masked o-benzoquinones
(MOBs).
MOBs are indeed highly reactive and versatile intermedi-
ates in organic synthesis.4 We have demonstrated that
these transients undergo the Diels–Alder reactions with an
array of dienophiles under mild conditions in excellent se-
lectivities enabling rapid access to highly functionalized
bicyclic and tricyclic ring systems from readily available
2-methoxyphenols.5 The intramolecular Diels–Alder re-
action (IMDA) of MOBs provided an expeditious entry to
polycyclic skeletons.6 The MOB Diels–Alder protocol
has been utilized as one of the key-steps in the total syn-
thesis of several natural products.7
Br
R2
OMe
OH
TMS
R2
OMe
OH
i) BuLi, TMSCl
DAIB
+
MeOH
ii) H
R1
R1
2a-c
1a-c
87-95%
Owing to their highly reactive nature, MOBs undergo fac-
ile dimerization to provide Diels–Alder type dimers.8 For
instance, the MOBs generated by the oxidation of guaia-
col and its 3- and 4-methyl derivatives are highly reactive
and produce large amounts of the corresponding dimers
even in the presence of large excess of external dineo-
phile. The reactivity of a particular MOB is a function of
substituent and substitution pattern. Recently, we have de-
duced a general trend for the stability and dimerization of
these labile quinones.5c,9 An electron-withdrawing group
at position-4 of MOB enhances its reactivity (i.e. facili-
X
OMe
R
TMS
R2
OMe
OMe
X
R
TMS
R2
OMe
O
R1
O
R1
4-6(a-c)
74-96%
3a-c
a: R1 = R2 = H
b: R1 = Me, R2 = H
c: R1 = H, R2 = Me
for MVK & 4: X = COMe, R = H
MA & 5: X = CO2Me, R = H
MMA & 6: X = CO2Me, R = Me
Scheme 1
Synlett 2002, No. 9, Print: 02 09 2002.
Art Id.1437-2096,E;2002,0,09,1520,1522,ftx,en;U01402ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Diels–Alder Reactions of Silyl-Substituted Masked o-Benzoquinones
1521
R
OH
n
Table 1 Synthesis of Alkenylsilanes 4a–c to 6a–c via the Inter-
molecular Diels–Alder Reactions of 4-Silyl-Substituted Masked
o-Benzoquinones 3a–c with Electron-Deficient Dienophilesa
( )
O
TMS
R2
OMe
OH
n
TMS
R2
7-10
OMe
DAIB
O
R
R1
R1
11-14(a-c)
Entry
Phenol MOB
Dienophile
Time
Adduct/
Yield (%)b
2a-c
1
2
3
4
5
6
7
8
9
2a
2a
2a
2b
2b
2b
2c
2c
2c
3a
3a
3a
3b
3b
3b
3c
3c
3c
MVK
MA
8 h
18 h
36 h
6 h
4a/88
5a/94
6a/74
4b/92
5b/96
6b/89
4c/91
5c/94
6c/77
a: R1 = R2 = H
b: R1 = Me, R2 = H
c: R1 = H, R2 = Me
( )
O
n
R
TMS
R2
MMA
MVK
MA
OMe
for 7,11,15: n = 1, R = H
8,12,16: n = 1, R = Me
9,13,17: n = 1, R = Ph
10,14,18: n = 2, R = H
R1
O
15-18(a-c)
60-85%
18 h
18 h
6 h
MMA
MVK
MA
Scheme 2
24 h
72 h
MMA
Table 2 Synthesis of Alkenylsilanes 15a–c to 18a–c via the
Intramolecular Diels–Alder Reactions of 4-Silyl-Substituted Masked
a All reactions were carried out at room temperature with 2 equiv of
dienophile.
o-Benzoquinones 11a–c to 14a–ca
b Yields are of pure and isolated products.
Alkenol
Entry Phenol MOB
n
R
Adduct/
Yield
(%)b
The reaction was then extended to silyl-phenols 2b,c.
Thus, the Diels–Alder reactions of MOBs 3b,c with
MVK, MA and MMA proceeded smoothly to furnish the
corresponding cycloadducts 4b,c–6b,c in excellent yields.
The results are presented in Table 1.
1
2
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
2c
2c
11a
12a
13a
14a
11b
12b
13b
14b
11c
12c
13c
14c
7
8
1
1
1
2
1
1
1
2
1
1
1
2
H
15a/68
16a/85
17a/60
18a/60
15b/73
16b/77
17b/66
18b/68
15c/78
16c/81
17c/74
18c/73
Me
Ph
H
3
9
To broaden the scope of this methodology, we then tested
the intramolecular Diels–Alder reactions of 4-silyl-substi-
tuted MOBs. As a preliminary case, the oxidation of 2c by
DAIB in the presence of allyl alcohol (7) and the subse-
quent cycloaddition were carried out under various condi-
tions. After considerable experimentation, the crude
MOB 11c that was obtained from the oxidation-step un-
derwent the internal Diels–Alder reaction to furnish 15c in
78% yield.12 Similarly, MOBs 12c–14c derived from 2-
methoxyphenol 2c and alkenols 8–10 reacted intramolec-
ularly to afford adducts 16c–18c, respectively, in very
good yields. Immediately, we extended this reaction to 4-
silyl-2-methoxyphenols 2a and 2b (Scheme 2). Thus, the
oxidation of 2a,b with DAIB in the presence of alkenols
7–10 generated MOBs 11a,b–14a,b, which underwent in-
ternal Diels–Alder reactions to provide silyl-substituted
oxatricycles 15a,b–18a,b in good yields. The results are
summarized in Table 2.
4
10
7
5
H
6
8
Me
Ph
H
7
9
8
10
7
9
H
10
11
12
8
Me
Ph
H
9
10
a All the Diels–Alder reactions of MOBs 11a–c to 14a–c were carried
out at 80 °C for 10 h.
b Yields are of pure and isolated products.
The inter- and intramolecular Diels–Alder reactions of 4-
silyl-substituted MOBs have proceeded in highly selec-
tive manner. The regio- and stereochemistry of these cy-
cloadducts were in accordance with literature
precedents5c,6a,13 and were thoroughly determined from
tries of the cycloadducts 6a–c derived from methyl meth-
acrylate were confirmed by comparing their 1H NMR data
with that of 19 (Figure 1), whose structure was known
from single-crystal X-ray diffraction method.8,14 Further,
the structure of 17b was confirmed by the single crystal
X-ray structure of 20 (Figure 1),15 which was derived
from 17b.
1
the H-1H decoupling NMR experiments. The stereo-
chemical assignments of adducts 4a,b, 5a,b and 15a,b–
18a,b were further confirmed from the observed long-
range W-coupling between the vinylic protons and the
methine/methylene proton. The regio- and stereochemis-
Synlett 2002, No. 9, 1520–1522 ISSN 0936-5214 © Thieme Stuttgart · New York

1522
C.-H. Lai et al.
LETTER
(5) (a) Chen, C.-H.; Rao, P. D.; Liao, C.-C. J. Am. Chem. Soc.
1998, 120, 13254. (b) Hsu, D.-S.; Rao, P. D.; Liao, C.-C.
Chem. Commun. 1998, 1795. (c) Liao, C.-C.; Chu, C.-S.;
Lee, T.-H.; Rao, P. D.; Ko, S.; Song, L.-D.; Shiao, H.-C. J.
Org. Chem. 1999, 64, 4102. (d) Hsieh, M.-F.; Rao, P. D.;
Liao, C.-C. Chem. Commun. 1999, 1441. (e) Yen, C.-F.;
Peddinti, R. K.; Liao, C.-C. Org. Lett. 2000, 2, 2909.
(f) Gao, S.-Y.; Lin, Y.-L.; Rao, P. D.; Liao, C.-C. Synlett
2000, 421. (g) Lin, K.-C.; Liao, C.-C. Chem. Commun.
2001, 1624.
(6) (a) Chu, C.-S.; Lee, T.-H.; Rao, P. D.; Song, L.-D.; Liao,
C.-C. J. Org. Chem. 1999, 64, 4111. (b) Chen, Y.-K.;
Peddinti, R. K.; Liao, C.-C. Chem. Commun. 2001, 1340.
(7) (a) Liu, W.-C.; Liao, C.-C. Synlett 1998, 912. (b) Liu,
W.-C.; Liao, C.-C. Chem. Commun. 1999, 117. (c) Hsu,
D.-S.; Hsu, P.-Y.; Liao, C.-C. Org. Lett. 2001, 3, 263.
(8) Lai, C.-H.; Shen, Y.-L.; Liao, C.-C. Synlett 1997, 1351.
(9) Yen, C.-F; Peddinti, R. K.; Liao, C.-C., unpublished results.
(10) General procedure for intermolecular Diels–Alder reaction:
To a stirred mixture of a 2-methoxyphenol (2a–c, 0.5 mmol)
and dienophile (2 equiv) in MeOH (25 mL) at room
temperature, was added DAIB (0.55 mmol, 1.1 equiv) at
once and the reaction was continued at the same
MeO2C
Br
Ph
TMS
O
OMe
OMe
OH
OMe
O
20
19
Figure 1
In summary, this Letter describes a general and efficient
methodology for the synthesis of silyl bicyclic and oxatri-
cyclic alkenes from easily accessible 2-methoxyphenols.
Utilization of these alkenylsilanes in organic synthesis is
under progress in our laboratory.
Acknowledgement
Financial support by the National Science Council of Republic of
China is appreciated. R. K. P thanks the NSC for a postdoctoral
fellowship.
temperature. After a period of time (see Table 1), the
reaction mixture was concentrated under reduced pressure
and purified by silica gel column chromatography to get the
pure adduct (4a–c to 6a–c).
References
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(11) All the new compounds were satisfactorily characterized by
IR, 1H NMR (400 MHz), and 13C NMR (100 MHz), DEPT,
and low and high resolution MS analyses.
(12) General procedure for intramolecular Diels–Alder
reaction: To a stirred mixture of a 2-methoxyphenol (2a–c,
0.5 mmol) and an alkenol (7–10, 25 mmol, 50 equiv) at 0 °C,
was added DAIB (0.55 mmol, 1.1 equiv) at once and the
contents were stirred for 30 min at the same temperature
[oxidations of 2-methoxyphenols in the presence of
cinnamyl alcohol (9) were carried out at room temperature
(entries 3, 7 and 11 in Table 2)]. The reaction was quenched
with aq NaHCO3, extracted with ether. The organic layer
was washed with brine, dried over anhyd. MgSO4, and
concentrated. The crude residue that contains mainly MOB
(11a–c to 14a-c) and excess alkenol (7–10) was heated at 80
°C for 10 h. The reaction mixture was then cooled to room
temperature, the excess alkenol was removed under reduced
pressure and the residue was subjected to silica gel column
chromatography to obtain the pure adduct (15a–c to 18a–c).
(13) (a) Katayama, S.; Hiramatsu, S.; Aoe, K.; Yamayuchi, M. J.
Chem. Soc., Perkin Trans. 1 1997, 561. (b) Gao, S.-Y.; Ko,
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Synlett 2002, No. 9, 1520–1522 ISSN 0936-5214 © Thieme Stuttgart · New York