Homo-cope-type five-carbon ring-expansion reaction via silyl enol ether

Article abstract of DOI:10.1055/s-2006-950264

A five-carbon ring-expansion reaction from a cyclohexane derivative fitted with a 3-hydroxy-2-silyloxyprop-1-en-1-yl unit in lieu of one of the C=C double bonds in the Cope rearrangement was studied to synthesize cycloundecanone derivatives. It was found that (E)-triethylsilyl enol ether is necessary for the reaction. The tras-isomer with respect to the cyclohexane ring afforded (2E,8E)-cycloundeca-2,8-dien-1-one, while its cis-isomer afforded (2E,8E)- and (2E,8Z)-isomers in a 1:3 ratio. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950264

2830
LETTER
Homo-Cope-Type Five-Carbon Ring-Expansion Reaction via Silyl Enol Ether
‘
H
omo’-Cope-T
y
h
pe Five-Carb
i
on Rin
a
g Expansio
k
n Reaction i Kuroda,*a Tadashi Ueshino,a Shigenobu Honda,a Hideyuki Suzukib
a
Department of Chemistry, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
Fax +81(3)39852396; E-mail: chkkuroda@grp.rikkyo.ne.jp
Research Foundation of Itsuu Laboratory, Tamagawa, Setagaya-ku, Tokyo 158-0094, Japan
b
Received 4 August 2006
SiMe3
OH
H
H
Abstract: A five-carbon ring-expansion reaction from a cyclohex-
ane derivative fitted with a 3-hydroxy-2-silyloxyprop-1-en-1-yl
unit in lieu of one of the C=C double bonds in the Cope rearrange-
ment was studied to synthesize cycloundecanone derivatives. It was
found that (E)-triethylsilyl enol ether is necessary for the reaction.
The trans-isomer with respect to the cyclohexane ring afforded
(2E,8E)-cycloundeca-2,8-dien-1-one, while its cis-isomer afforded
(2E,8E)- and (2E,8Z)-isomers in a 1:3 ratio.
1
Tf2O
2,6-lutidine
H
Key words: ring expansion, carbocycles, silicon, enol ethers, Cope
rearrangement
SiMe3
OTf
H
The Cope rearrangement including the oxy-Cope rear-
rangement is one of the fundamental reactions, which pro-
vides a useful method for a four-carbon ring expansion
reaction in organic synthesis.1 For example, the germacra-
ne type of ten-membered carbocycle was synthesized
from the easily available six-membered ring compound.2
In addition, 2-(trimethylsilylmethyl)acrylate or 2-(tri-
methylsilylmethyl)allylalcohol derivatives are versatile
carbon 1,3-dipole equivalents, and the replacement of a
C=C double bond in some organic reactions with these
units enables ‘homo’-type reactions. The [4+3] cycloaddi-
tion reaction (‘homo-Diels–Alder’ reaction),3 and related
reactions are documented in review articles.4 We reported
the synthesis of a-methylene-g-lactones5 and related
compounds6 using these moieties.7
2
Scheme 1
Here we report that the reaction occurs when TES enol
ether was employed as the substrate.
Following the previous report, we studied the five-carbon
ring expansion reaction from six- to eleven-membered
carbocycles. These carbocyclic systems are found in nat-
ural terpenes, such as humulanes in sesquiterpenes9,10 and
dollabelanes in diterpenes.9,11
As the substrates of the ‘homo-Cope’ reaction, three silyl
ethers, TBS 3a, TBDPS 3b, and TES 3c were prepared via
a modified Horner–Wadsworth–Emmons (HWE) reac-
tion, which is an analogous method to the synthesis of the
corresponding allylsilane.8 The HWE reagents 4a–c were
prepared by coupling diethyl phosphite (5) and methyl 2-
hydroxy-2-methoxyacetate (6)12 followed by silylation of
the condensation product 7 (Scheme 2). The HWE reac-
tion of 8, obtained by the Swern oxidation of 9,8 with 4a
and 4b was carried out in accordance with Schmidt’s
method12 giving the corresponding products in 95% (E/
Z, 91:9) and 62% (E/Z, 77:23) yields, respectively, from
which the E-isomers 10a and 10b were separated by silica
gel chromatography. For the synthesis of 10c, LDA was
used instead of 1,1,3,3-tetramethylguanidine (75% yield;
E/Z, 94:6)13 (Scheme 3). The E-isomer 10c could not be
separated from its Z-isomer in pure form, and therefore,
the mixture was used in the following study. Compounds
3a–c were obtained when 10a–c were treated with
DIBAL-H in hexane–Et2O, while the reduction in CH2Cl2
gave only complex mixtures.
During the course of our studies on the ‘homo’ reaction,
we recently reported a new five-carbon ring expansion re-
action by replacing one of the C=C double bonds in the
Cope rearrangement with a 3-hydroxy-2-(trimethylsilyl-
methyl)prop-1-en-1-yl moiety (Scheme 1).8 Although the
reaction is a ‘homo’ analogue of the Cope rearrangement,
its mechanism is considered to be stepwise, which pro-
ceeds after conversion of the hydroxy group in 1 to triflu-
oromethanesulfonate, giving eleven-membered ring
compound 2. We supposed that the reaction is more useful
in organic synthesis if the ring expansion product has an
oxygen function, rather than hydrocarbon. With this in
mind, we planned to use a silyl enol ether instead of the
allylsilane since the product is expected to have an enone
group which may be useful for further transformations.
SYNLETT 2006, No. 17, pp 2830–2832
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7
.1
0
.2
0
0
6
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950264; Art ID: U09506ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Homo-Cope-Type Five-Carbon Ring-Expansion Reaction
2831
(EtO)2P(O)H
(MeO)CH(OH)COOMe
+
The reaction from a substrate having a tert-butyl substitu-
ent on the cyclohexane ring was also studied (Scheme 5).
The TES enol ether 12 (E/Z, 87:13) was prepared analo-
gously from 138 via DIBAL-H reduction of 14. Since (E)-
12 and (Z)-12 could be separated from each other, the
ring-expansion reaction of both isomers was examined.
The reaction proceeded smoothly from (E)-12 to afford
1516 in 71% yield, while (Z)-12 afforded a complex mix-
ture. This indicated that (E)-silyl enol ether is necessary
for the ring-expansion reaction. These results are in con-
trast to the case of the corresponding allylsilane, in which
the Z-isomer also afforded the eleven-membered carbocy-
cle via a Z to E isomerization, although its yield was low.8
Those results indicate that Z to E isomerization of silyl
enol ether did not occur.
5
6
i
(EtO)2P(O)CH(OH)COOMe
ii
7
(EtO)2P(O)CH(OR)COOMe
4a R = TBS
4b R = TBDPS
4c R = TES
Scheme 2 Reagents: (i) see ref. 12; (ii) RCl, imidazole, DMF.
H
H
H
H
ref. 8
COOH
COOH
OH
i
9
OTES
H
H
H
H
CHO
CHO
i
COOMe
t-Bu
t-Bu
8
H
H
14
iii
H
ii
13
ii
OR
COOMe
OTES
OTES
OH
OTES
H
H
H
H
COOMe
+
OH
t-Bu
t-Bu
H
H
H
10a R = TBS
10b R = TBDPS
10c
(E)-12
(E)-12
(Z)-12
O
iv
iv
iii
iii
OR
H
OTES
OH
H
t-Bu
(Z)-12
15
OH
Scheme 5 Reagents: (i) 4c, LDA, THF; (ii) DIBAL-H, Et2O; (iii)
Tf2O, 2,6-lutidine, CH2Cl2.
H
H
3a R = TBS
3c
3b R = TBDPS
In order to determine the stereochemistry with respect to
the cyclohexane ring, the cis-substituted diastereomer was
prepared from cis-1,2-cyclohexanedicarboxylic acid
(Scheme 6). However, since isomerization occurred dur-
ing the preparation, only a mixture of 18 and 3c (68:32)
could be obtained. When this mixture was treated with
Tf2O and 2,6-lutidine as above, a mixture of 11 and its 8Z-
isomer 1917 was obtained in a 46:54 ratio. The geometry
of the double bonds in 19 was determined to be 2E,8Z
based on the coupling constants in the 1H NMR spectrum.
Since 3c afforded only 11, it can be deduced that 18 gives
11 and 19 in approximately a 1:3 ratio. This result is
roughly consistent with our previous observation for the
corresponding allylsilane.8
Scheme 3 Reagents: (i) DMSO, (COCl)2, Et3N, CH2Cl2; (ii) 4a or
4b, LiCl, 1,1,3,3-tetramethylguanidine, THF; (iii) 4c, LDA, THF; (iv)
DIBAL-H, Et2O.
The ring expansion reaction was then studied. When 3c
was treated with Tf2O and 2,6-lutidine in CH2Cl2 at room
temperature,8,14 the expected product 1115 was obtained in
69% yield (Scheme 4) without the accompanying normal
Cope rearrangement product. However, compounds 3a
and 3b afforded only complex mixtures under the same
reaction conditions. The reaction of 3a was studied under
various conditions but was unsuccessful. The geometry of
the two double bonds in 11 was determined to be 2E,8E
based on coupling constants (15.5 Hz, 16.2 Hz) in the 1H
NMR spectrum.
In conclusion, a new enol homo-Cope-type five-carbon
ring-expansion reaction was established, which provides a
new entry to cycloundecane derivatives. This method is
considered to be more useful than the previously reported
reaction of the corresponding allylsilane, since the prod-
uct has an enone group, and therefore, further reactions
such as alkylation can be performed easily.
O
3c
11
Scheme 4 Reagents: Tf2O, 2,6-lutidine, CH2Cl2.
Synlett 2006, No. 17, 2830–2832 © Thieme Stuttgart · New York

2832
C. Kuroda et al.
LETTER
H
H
(7) (a) Kuroda, C. Recent Res. Dev. Pure Appl. Chem. 1998, 2,
184. (b) Kuroda, C.; Suzuki, H. Curr. Org. Chem. 2003, 7,
115.
H
H
CHO
COOH
+ 8
(8) Suzuki, H.; Kuroda, C. Tetrahedron 2003, 59, 3157.
(9) Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring
Compounds, Vol. 2; Academic Press: New York, 1972.
(10) For recent examples: (a) Fraga, B. M. Nat. Prod. Rep. 2000,
17, 483. (b) Fraga, B. M. Nat. Prod. Rep. 2001, 18, 650.
(c) Fraga, B. M. Nat. Prod. Rep. 2002, 19, 650. (d) Fraga,
B. M. Nat. Prod. Rep. 2003, 20, 392. (e) Fraga, B. M. Nat.
Prod. Rep. 2004, 21, 669. (f) Fraga, B. M. Nat. Prod. Rep.
2005, 22, 465.
COOH
i
16
OTES
H
COOMe
+ 10c
H
17
ii
(11) For recent examples: (a) Hanson, J. R. Nat. Prod. Rep. 2000,
17, 165. (b) Hanson, J. R. Nat. Prod. Rep. 2001, 18, 88.
(c) Hanson, J. R. Nat. Prod. Rep. 2002, 19, 125.
OTES
H
(d) Hanson, J. R. Nat. Prod. Rep. 2003, 20, 70. (e) Hanson,
J. R. Nat. Prod. Rep. 2004, 21, 785. (f) Hanson, J. R. Nat.
Prod. Rep. 2005, 22, 594.
+ 3c
OH
H
iii
(12) Schmidt, U.; Langner, J.; Kirschbaum, B.; Braun, C.
Synthesis 1994, 1138.
18
O
(13) Nakamura, E. Tetrahedron Lett. 1981, 22, 663.
(14) Five-Carbon Ring Expansion: In a 100-mL round-bottomed
flask, a solution of 3c (114.4 mg, 0.386 mmol) in anhyd
CH2Cl2 (40 mL) was prepared at –60 °C under Ar. To this
was added 2,6-lutidine (0.13 mL) and Tf2O (0.1 mL)
successively with stirring; stirring was continued for 1 h at
the same temperature. A sat. aq solution of NH4Cl was added
and the mixture was extracted with CH2Cl2. The organic
layer was dried and the solvent was evaporated to afford an
oily residue, which was chromatographed on silica gel (3 g;
hexane–EtOAc, 95:5) to give 11 (43.7 mg, 69%).
+ 11
19
Scheme 6 Reagents: (i) 4c, LDA, THF; (ii) DIBAL-H, Et2O; (iii)
Tf2O, 2,6-lutidine, CH2Cl2.
Acknowledgment
(15) Compound 11: Oil. IR (neat): 1657 cm–1. 1H NMR (CDCl3):
d = 1.47–1.80 (4 H, m), 2.01–2.10 (2 H, m), 2.21–2.30 (4 H,
m), 2.61–2.67 (2 H, m), 5.03 (1 H, dt, J = 15.5, 7.6 Hz,
CH=CH), 5.31 (1 H, dt, J = 15.5, 7.7 Hz, CH=CH), 5.90 (1
H, d, J = 16.2 Hz, CH=CHCO), 6.31 (1 H, dt, J = 16.2, 7.5
Hz, CH=CHCO). 13C NMR (CDCl3): d = 27.28, 28.53,
30.07, 34.21, 34.45, 38.59, 128.81, 132.01, 137.38, 156.96,
202.88. HRMS: m/z calcd for C11H16O (M+): 164.1201;
found: 164.1235.
Financial support was partly obtained from the Frontier Project of
Rikkyo University.
References and Notes
(1) Hill, R. K. In Comprehensive Organic Synthesis, Vol. 5;
Trost, B. M., Ed.; Pergamon: Oxford, 1991, 785–826.
(2) (a) Still, W. C.; Murata, S.; Revial, G.; Yoshihara, K. J. Am.
Chem. Soc. 1983, 105, 625. (b) Kuroda, C.; Nakamura, T.;
Hirota, H.; Enomoto, K.; Takahashi, T. Bull. Chem. Soc.
Jpn. 1985, 58, 146.
(16) Compound 15: Oil. IR (neat): 1658 cm–1. 1H NMR (CDCl3):
d = 0.87–0.96 (1 H, m), 0.89 (9 H, s, t-Bu), 1.15 (1 H, dddd,
J = 2.3, 3.5, 12.5, 14.6 Hz), 1.54 (1 H, dt, J = 12.5, 10.0 Hz),
1.93 (1 H, ddt, J = 1.4, 9.5, 12.5 Hz), 2.07 (1 H, ddt, J = 5.6,
14.6, 2.5 Hz), 2.17–2.37 (3 H, m), 2.44–2.54 (2 H, m), 2.81
(1 H, dt, J = 2.5, 11.3 Hz), 5.08–5.20 (1 H, m, CH=CH), 5.30
(1 H, br dt, J = 15.7, 7.5 Hz, CH=CH), 5.90 (1 H, br d,
J = 16.1 Hz, CH=CHCO), 6.45 (1 H, ddd, J = 6.0, 9.4, 16.1
Hz, CH=CHCO). 13C NMR (CDCl3): d = 27.14 (3 C), 30.07,
31.07, 34.20, 34.42, 35.03 (br), 38.86, 49.56, 129.12 (br),
132.31, 136.33, 156.27, 202.97. HRMS: m/z calcd for
C15H24O (M+): 220.1827; found: 220.1812.
(3) Giguere, R. J.; Duncun, S. M.; Bean, J. M.; Purvis, L.
Tetrahedron Lett. 1988, 29, 6071.
(4) (a) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1986, 25, 1.
(b) Harmata, M. Tetrahedron 1997, 53, 6235. (c) Chan, D.
M. T. In Cycloaddition Reactions in Organic Synthesis;
Kobayashi, S.; Jørgensen, K. A., Eds.; Wiley: Weinheim,
2002, 57–84; see also ref. 7.
(5) (a) Kuroda, C.; Kobayashi, K.; Koito, A.; Anzai, S. Bull.
Chem. Soc. Jpn. 2001, 74, 1947. (b) Kuroda, C.; Ito, K.
Bull. Chem. Soc. Jpn. 1996, 69, 2297.
(6) For examples (a) Kuroda, C.; Okada, M.; Shinozaki, S.;
Suzuki, H. Tetrahedron 2006, 62, 726. (b) Kuroda, C.;
Honda, S.; Nagura, Y.; Koshio, H.; Shibue, T.; Takeshita, T.
Tetrahedron 2004, 60, 319. (c) Kuroda, C.; Kasahara, T.;
Akiyama, K.; Amemiya, T.; Kunishima, T.; Kimura, Y.
Tetrahedron 2002, 58, 4493. (d) Kuroda, C.; Koshio, H.;
Koito, A.; Sumiya, H.; Murase, A.; Hirono, Y. Tetrahedron
2000, 56, 6441.
(17) Compound 19: Oil. IR (neat): 1672 cm–1. 1H NMR (CDCl3):
d =1.64–1.74 (4 H, m), 2.17–2.31 (6 H, m), 2.53–2.57 (2 H,
m), 5.36–5.43 (1 H, m, CH=CH), 5.52 (1 H, ddt, J = 10.5,
8.2, 1.7 Hz, CH=CH), 6.19 (1 H, dt, J = 16.2, 1.5 Hz,
CH=CHCO), 6.80 (1 H, dt, J = 16.2, 6.7 Hz, CH=CHCO).
13C NMR (CDCl3): d = 22.92, 25.10, 25.15, 28.50, 32.10,
39.81, 128.81, 129.73, 131.57, 151.11, 203.56. HRMS: m/z
calcd for C11H16O (M+): 164.1201; found: 164.1221.
Synlett 2006, No. 17, 2830–2832 © Thieme Stuttgart · New York