Boron trichloride mediated regioselective Claisen rearrangement of resorcinol derivatives: Application to resorcinol carvonyl ethers

Article abstract of DOI:10.1055/s-2007-983712

Claisen rearrangement (CR) of resorcinol allyl ethers was examined. Although thermal CR gave low regioselectivity, the selectivity was much improved in the presence of a Lewis acid such as boron trichloride. This rearrangement was successfully applied to resorcinol carvonyl ethers for the regioselective introduction of a carvone unit into the resorcinol skeleton for the synthesis of phytoestrogenic miroestrols. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-983712

PAPER
1785
Boron Trichloride Mediated Regioselective Claisen Rearrangement of
Resorcinol Derivatives: Application to Resorcinol Carvonyl Ethers
Boron
Trichlou
m
d
Claise
n
Rearrange
i
ment
o
h
f
Resorcinol
i
D
eriva
r
tive
s
o Ito, Keiko Fusegi, Takuya Kumamoto,* Tsutomu Ishikawa
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Fax +81(43)2902911; E-mail: tkuma@p.chiba-u.ac.jp
Received 1 March 2007; revised 20 April 2007
Abstract: Claisen rearrangement (CR) of resorcinol allyl ethers
2
RO
O
RO
OH
RO
OH
was examined. Although thermal CR gave low regioselectivity, the
selectivity was much improved in the presence of a Lewis acid such
as boron trichloride. This rearrangement was successfully applied to
resorcinol carvonyl ethers for the regioselective introduction of a
carvone unit into the resorcinol skeleton for the synthesis of phy-
toestrogenic miroestrols.
+
6
1a: R = Me
1b: R = TBS
2a: R = Me
2b: R = TBS
3a: R = Me
3b: R = TBS
MeO
X
O
MeO
OH
2
Key words: carvone, boron trichloride, rearrangement, regioselec-
tivity, resorcinol
MeO
X
OH
+
6
X
4
5
6
(X = -CH=CHCO2Me)
The Claisen rearrangement (CR)1 is a versatile carbon–
carbon bond-forming reaction whose aromatic version
has been successfully used to introduce a C3-unit at the
ortho position of phenols. However, the thermal CR of re-
sorcinol derivatives (e.g., 1, Figure 1) to give 6-isomers 2
and 2-isomers 3 as rearranged products (Scheme 1) usual-
ly proceeds with low regioselectivity.2,3 Several examples
of regioselective rearrangement have been reported: for
example, the photo-CR of the methoxy-substituted deriv-
ative 1a in the presence of a-cyclodextrin affords 6-allyl-
3-methoxyphenol (2a) exclusively.4 Regioselective Lewis
acid mediated CR of allyl ethers has also been reported.
For example, CR of the TBS-substituted derivative 1b in
the presence of diethylaluminum chloride (Et2AlCl) gave
a 6:1 mixture of 2b and 3b,5 and BF3·OEt2-mediated CR
of the 1,1-dimethylallyl ether of the cinnamate derivative
4 gave a 10:1 mixture of 5 and 6.6 In these cases, 6-isomer
2b or 5 was predominantly formed (Scheme 1).
Scheme 1 Reported CR of resorcinol derivatives 1 and 4
the resorcinol carvonyl ether 10 is the key step for the in-
troduction of (R)-carvone (11) to the A ring, as shown in
Scheme 2.9 In this article, we report in detail on our study
of the regioselective CR of simple resorcinol derivatives
and its application to carvonyl ethers for the synthesis of
phytoestrogenic miroestrols.
HO
O
H
RO
OH
O
Y
H
A
H
OH
OH
O
9
7 (Y = OH): (+)-miroestrol
8 (Y = H): (+)-deoxymiroestrol
CR
RO
O
H
H
RO
O
10
1
O
O
10
11
a: R = Me
e: R = Bz
b: R = TBS f: R = H
c: R = TIPS
d: R = TBDPS
Scheme 2 Retrosynthesis of (+)-miroestrol (7) and (+)-deoxy-
miroestrol (8)
Figure 1 The structure of the substrate 1 for CR
Starting resorcinol allyl ethers 1 (shown in Figure 1) were
As a part of our study of the chemical components of the prepared by conventional methods.3 1-Allyloxy-3-silyl-
Thai miracle herb ‘kwao keur’ (identified as Pueraria oxybenzenes 1b–d were prepared by successive reactions
mirifica),7 we have sought to synthesize the strongly phy- of allylation of resorcinol monobenzoate (12e), hydrolysis
toestrogenic compounds (+)-miroestrol (7)8 and (+)- of the corresponding benzoate 1e to resorcinol 1f, and si-
deoxymiroestrol (8). In our strategy, regioselective CR of lylation. TBDPS-substituted crotyl 13 (Z = H) and prenyl
derivatives 13 (Z = Me) were obtained in a similar manner
from 12e using crotyl chloride or 3,3-dimethylallyl bro-
mide, respectively (Figure 2).
SYNTHESIS 2007, No. 12, pp 1785–1796
Advanced online publication: 08.06.2007
x
x.
x
x
.
2
0
0
7
DOI: 10.1055/s-2007-983712; Art ID: F04407SS
© Georg Thieme Verlag Stuttgart · New York

1786
F. Ito et al.
PAPER
Table 2 Effects of Lewis Acids on CR of Methyl Ether 1a
TBDPSO
O
Z
BzO
OH
Lewis acid
(3 equiv)
MeO
O
MeO
OH
MeO
OH
Me
12e
+
CH2Cl2
–50 °C
13: Z = H or Me
1a
2a
OH
3a
Figure 2 Structures of substrates 13 for CR and starting material
MeO
MeO
O
12e
+
+
12a
14
First we examined the microwave (MW)-mediated ther-
mal CR10 (Table 1). Reaction of allyl 3-methoxyphenyl
ether (1a) at 250 °C in N,N-diethylaniline (PhNEt2) as a
solvent gave rearranged products 2a and 3a in 48 and 32%
yield, respectively (entry 1). The regioselectivity was not
improved by lowering the reaction temperature (entry 2),
and CR of the corresponding silyloxy derivatives did not
give improved regioselectivity (entries 3-5). However, ef-
fective conversions were observed in the latter rearrange-
ments, independent of the size of silyloxy substituents.
Entry
Lewis acid Time (h)
Yield (%)a
1a
0
2a
62
59
3a
Others
1
2
BCl3
1
1
11
2
12a (8%)
AlCl3
0
12a (5%),
14 (6%)
3b
Et2AlCl
5.5
35
44
6
–
a Isolated yield.
b The reaction mixture was gradually warmed to –20 °C.
Table 1 MW-Mediated Thermal CR of Resorcinol Allyl Ethers 1
RO
O
RO
OH
RO
OH
MW
Next, the BCl3-mediated CR of allyl ethers 1 with various
silyloxy substituents at the meta position was examined
(Table 3). Compared with the result of methyl ether 1a,
both chemical yield and regioselectivity were improved in
every case. As the bulkiness of the silyl group increased,
the chemical yield increased and the regioselectivity im-
proved (entries 2–4). For the CR of TBS ether 1b (entry
2), the regioselectivity found was very similar to that ob-
served previously using Et2AlCl as a Lewis acid.5 For the
CR of TBDPS ether 1d (entry 4), the total chemical yield
and selectivity were up to 95% and 8.5:1, respectively.
+
PhNEt2
1
2
3
Entry R in 1
Conditionsa
Yield (%)b
2
3
Total
1
2
3
4
5
1a: Me
250 °C, 30 min
48
32
11c
34
36
34
80
28
89
94
95
1a: Me
100–180 °C, 75 min 17c
1b: TBS
1c: TIPS
250 °C, 30 min
250 °C, 30 min
55
58
61
Table 3 BCl3-Mediated CR of 1 with Various Meta Substituents
1d: TBDPS 250 °C, 30 min
a MW condition: Discover (CEM), 300 W, 47–48 psi.
b Isolated yield, unless otherwise noted.
RO
O
RO
OH
RO
OH
BCl3
+
c Estimated by 1H NMR spectroscopy.
CH2Cl2
–50 °C
1
2
3
Next, we examined the Lewis acid-mediated CR of meth-
yl ether 1a (Table 2). High regioselectivity was observed
in the presence of an excess (3 equiv) of boron trichloride,
to give rearranged products 2a and 3a in 62 and 11%
yield, respectively, albeit with concomitant generation of
the deallylated product 12a in 8% yield (entry 1). The re-
action of 1a with aluminum trichloride yielded 2a as a ma-
jor product with the better regioselectivity of 30:1, but the
yield was slightly decreased due to the formation of
byproducts such as 12a (5%) and dihydrobenzofuran 1411
(6%) (entry 2). The weaker Lewis acid Et2AlCl gave no
by-products (entry 3), but the reaction did not go to com-
pletion and the selectivity was not better than that in the
reaction with BCl3. Thus, BCl3 was found to be the most
suitable reagent for this reaction.
Entry R in 1
BCl3
Time
(h)
Yield (%)a
(equiv)
2
3
Total
73
1b
2
1a: Me
3
3
3
3
1
1
1
1
1
1
1
5
62
75
77
85
84
77
11
13
11
10
8
1b: TBS
88
3
1c: TIPS
88
4
1d: TBDPS
1d: TBDPS
1d: TBDPS
95
5
92
6c
5
82
b The data from entry 1 in Table 2.
b Isolated yield.
c The reaction was carried out at –78 °C.
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

PAPER
Boron Trichloride Mediated Claisen Rearrangement of Resorcinol Derivatives
1787
Reaction with 1 equivalent of BCl3 (entry 5) gave almost 13 (Z = Me) at lower temperature, but the yield of 4-iso-
the same yield and selectivity as that with three equiva- mer 21 increased (entry 4).14 The ratio of normal/abnor-
lents of BCl3 (entry 4). The selectivity was improved to mal Claisen product was estimated to be 3:1 to 5:1, which
15:1 when the reaction was carried out at –78 °C (entry 6). is similar to the ratio obtained previously using the simple
phenyl ether 17.12,13 Unexpectedly, the BCl3-mediated CR
Furthermore, the CRs of the crotyl 13 (Z = H) and prenyl
of 13 (Z = Me) afforded the desired compound 15
ethers 13 (Z = Me) with a silyloxy substituent were exam-
(Z = Me) in a low yield of 26% (entry 5).
ined (Table 4). Under MW-mediated condition, the CR of
13 (Z = H) mainly afforded the 6-isomer 15 (Z = H) (en-
O
OH
OH
Me
try 1). The regioselectivity was estimated to be 4:1, which
was higher than that obtained for the simple allyl ether 1d
(see entry 5 in Table 1). BCl3-mediated CR improved the
regioselectivity to 10:1 (entry 2).
Me
Me
Me
Me
Me
17
18
19
Table 4 CR of Crotyl 13 (Z = H) and Prenyl Ether 13 (Z = Me)
OH
TBDPSO
O
Me Me
Z
20
13
(Z = H or Me)
Me
Figure 3 The structures of phenyl prenyl ether (17) and its rear-
ranged products
Z
TBDPSO
OH
TBDPSO
OH
Me
TBDPSO
OH
+
+
Finally, we subjected the resorcinol carvonyl ethers 10 to
CR in order to introduce a carvone unit into the resorcinol
skeleton. The starting carvonyl ethers 10 were prepared as
follows: direct displacement of the chlorine atom of 10-
chlorocarvone (24)15 with resorcinol monomethyl ether
(12a) in the presence of K2CO3 afforded the correspond-
ing 3-methoxyphenyl ether 10a. On the other hand, carvo-
nylation of resorcinol monobenzoate (12e) yielded the
desired benzoate 10e and resorcinol carvonyl ether (10f)
by partial hydrolysis of 10e in the reaction course in 40
and 18% yield, respectively. Thus, complete hydrolysis of
the crude mixture of the last reaction gave 10f in 70%
yield. The corresponding isopropyl 10g and TBDPS de-
rivatives 10d were obtained by alkylation or silylation, re-
spectively, of the phenol 10f (Scheme 3).
Me
15
Z
12d
16
TBDPSO
OH
TBDPSO
+
Me
O
TBDPSO
Me
OH
+
Me
Me
Me
23
Me
Me
21
22
Entry Z in 13 Conditionsa
Yield (%)b
15
64
85
0
16
14
8
12d 21
22
23
1
2
3
4
5
Hc
A
B
A
C
B
0
4
0
0
0
0
0
0
7
0
0
Hc
Me
Me
Me
0
10
3
58
68
0
14
12
0
a
RO
O
RO
OH
Cl
10a
10e
0
0
+
b
c
Cy
Cy
10f
d
+
26
0
32
10
12
24
a Conditions; A: in PhNEt2, MW, 250 °C, 0.5 h; B: BCl3 (1 equiv), in
CH2Cl2, –50 °C, 1 h; C: in PhNEt2, MW, 200 °C, 0.5 h.
b Isolated yield.
a: R = Me
e: R = Bz
f: R = H
a: R = Me
e: R = Bz
10f
10g
10d
e
H
Cy =
g: R = i-Pr
c A 5:1 trans/cis mixture.
d: R = TBDPS
O
The thermal CR of phenyl prenyl ether (17) has been re-
ported to generate 4-isomer 18, through a double rear-
rangement, and the abnormal Claisen product 19 in
around 72 and 30% yield, respectively, without the forma-
tion of the normal Claisen product 20 (Figure 3).12,13 In-
deed, we found that thermal CR of the prenyl ether 13
(Z = Me) gave neither the 6-isomer 15 (Z = Me) nor the 2-
isomer 16 (Z = Me); rather, the double rearranged 4-iso-
mer 21 was formed as a major product in 58% yield to-
gether with three other products, namely the phenol 12d
(10%), the abnormal Claisen product 22 (14%), and its cy-
clized product 23 (7%) (entry 3). Generation of the abnor-
mal Claisen product 22 was not suppressed in the CR of
Scheme 3 Synthesis of resorcinol carvonyl ethers 10. Reagents and
conditions: (a) from 12a: K2CO3, DMF, 70 °C, 9 h, 77%; (b) from
12e: K2CO3, DMF, 60 °C, 6 h, 40% for 10e, 18% for 10f; (c) from
12e: 1. K2CO3, DMF, 60 °C, 6 h, 2. KOH, MeOH, 0 °C, 30 min, 70%;
(d) 2-bromopropane, K2CO3, DMF, 50 °C, 4 h, 85%; (e) TBDPSCl,
imidazole, DMF, r.t., 4 h.
Similar to the case of the simple resorcinol allyl ethers 1,
the MW-mediated CR of 10 gave 6-carvonyl resorcinols
9 and 2-carvonyl resorcinols 25 in unsatisfactory yield
and regioselectivity. Hence, we examined BCl3-mediated
CR (Table 5). When the methoxy 10a and phenolic 10f
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

1788
F. Ito et al.
PAPER
Table 5 BCl3-Mediated CR of Resorcinol Carvonyl Ethers 10
RO
O
RO
OH
OH
Cl
Cy
+
+
6
2
Cy
Cy
Cy
OR
10
9
25
24
Entry
R in 10
Conditions
Yield (%)a
9
25
10
9
24
19
8
1
2
3
4
5
10a: Me
10f: H
–50 to –20 °C, 3 h
–50 °C, 3 h
54
51
23
10e: Bn
10g: i-Pr
–50 °C, 1 h
9
33
17
0
–50 °C, 1 h
5b
76c
10d: TBDPS
–50 °C, 1 h
6c
a Isolated yields from corresponding 10 unless otherwise noted.
b A 4: 1 mixture of 9g and 25g.
c Isolated yields from 10f in two steps.
derivatives were used as substrates (entries 1,2), the regio- Dehydrogenation of 35 with DDQ yielded the enal 36 (E/
selectivities were almost the same as that obtained in the Z = 1:3), which was subjected to selective reduction of the
CR of 1a; by contrast, the reaction with the benzoyloxy- aldehyde moiety with sodium triacetoxyborohydride
substituted ether 10e (entry 3) proceeded with a lower re- [NaBH(OAc)3]19 followed by separation of diastereoiso-
gioselectivity than was observed for the CR of 1a. The mers by column chromatography, to give the Z-alcohol
isopropyl derivative 10g gave a complex mixture contain- (Z)-37 and E-alcohol (E)-37 in 60% and 13% yield, re-
ing small amounts of 9g, 25g and 24 because of the labil- spectively. The relative configuration of each isomer was
ity of the isopropyl group under acidic conditions (entry
4). As expected, the yield and regioselectivity were im-
proved (9d:25d = 13:1, 76% yield for 9d) when the
TBDPS ether 10d was used (entry 5).
Introduction of a halogen or oxygen function into the car-
vone unit in the desired rearranged product 9d was at-
tempted, because these functions play an important role in
later steps in our synthetic strategy (Scheme 4). Direct al-
lylic chlorination on 26, which was prepared by benzyla-
tion of the phenol 9d via the same procedure as was used
to prepare 10-chlorocarvone (24) from carvone (11), af-
forded the chlorobenzene 27 but not the desired allylic
chloride 28. Therefore, we tried a stepwise procedure via
epoxide 29 starting from 26.
Epoxidation of 26 with MCPBA afforded the correspond-
ing epoxide 29 as a 1.2:1 mixture of diastereoisomers.
First, the rearrangement of 29 to allyl alcohol 31 under ba-
sic conditions was examined. No reaction occurred when
epoxide 29 was treated with two equivalents of LDA, and
the addition of HMPA resulted in a complex mixture.
Treatment of epoxide 29 with TMSOTf in the presence of
Scheme 4 Reagents and conditions: (a) benzyl bromide, KI,
Et3N16 followed by deprotection of the newly introduced
K2CO3, DMF, r.t., 3 h, 94%; (b) from 26: Ca(OCl)2, CH2Cl2, H2O,
TMS group afforded the eucarvone derivative 30. The for-
mation of 30 can be plausibly explained by the mecha-
nism shown in Scheme 5, in which the silyl enol ether 32
is converted into the [4.1.0] bicyclic system 33 followed
by expansion to the seven-membered ring product 34 ac-
companying desilylation.17
SiO2, r.t., 6 h, 48%; (c) from 26: MCPBA, CH2Cl2, –10 °C, 18 h, 67%;
(d) 1. TMSOTf, Et3N, CH2Cl2, 0 °C, 30 min, 2. alumina column chro-
matography, 3. TsOH·H2O, MeOH, r.t., 30 min, 47%; (e) BF3·OEt2,
CH2Cl2, –20 °C, 40 min, 49% from 26; (f) DDQ, benzene, reflux, 7 h,
53%, E/Z = 1: 3; (g) NaBH4, AcOH, benzene, reflux, 2.5 h, then se-
paration, 60% for (Z)-37, 13% for (E)-37 from 35; (h) MEMCl, i-
PrNEt2, DMF, 60 °C, 2 h, 81% for (Z)-38, 91% for (E)-38; (i) hn, ben-
zene, acetophenone, r.t., 1 h, 41% for (Z)-38, 29% recovery for (E)-
38.
On the other hand, treatment of epoxide 29 with BF3·OEt2
gave aldehyde 35 as a 1:1 mixture of diastereoisomers.18
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

PAPER
Boron Trichloride Mediated Claisen Rearrangement of Resorcinol Derivatives
1789
MHz), using tetramethysilane (0.00 ppm) as an internal standard;
13C NMR spectra were recorded on JEOL JNM-ECP400 (100 MHz)
or -ECP600 (150 MHz), using the middle resonance of CDCl3 (77.0
ppm) as an internal standard; d in ppm, J in Hz, dif. = diffused.
EIMS were recorded on a JEOL GC-Mate with direct inlet. FABMS
were recorded on a JMS-HX110 with m-nitrobenzyl alcohol as a
matrix. SiO2 60 F254 (Merck) was used for TLC, and SiO2 60 (Kan-
to Chemicals, No. 375674-85) or Al2O3 (Merck, 1097) for column
chromatography (CC). Biotage Horizon system was used for flash
chromatography. Anhyd CH2Cl2, Et2O, and DMF were purchased
from Kanto Chemicals. Anhyd THF was purchased from Wako
Chemicals. Microwave irradiation was done in a CEM Discover
system in a sealed tube.
:B
TMS
Ar
TMSO
Ar
H
O
H
H
29
H
Me
OTMS
TMSO
Me
32
33
OTMS
Ar
30
Me
TMSO
34
2-Allyoxyphenol (1f)
To a mixture of 12e (507 mg, 2.32 mmol) and K2CO3 (672 mg, 4.87
mmol) in DMF (2 mL), was added allyl bromide (0.31 mL, 3.51
mmol) and the mixture was stirred at 60 °C for 2 h. After cooling,
sat. aq NH4Cl (5 mL) and H2O (5 mL) were added and the mixture
was extracted with Et2O (3 × 20 mL). The organic layer was washed
with H2O (5 × 10 mL) and brine (1 × 10 mL), then dried (MgSO4).
The solvent was evaporated in vacuo to give crude 1e as a yellow
oil (578 mg). To the solution of crude 1e in MeOH (2 mL), was add-
ed a solution of KOH in MeOH (2 mL) at r.t. and the whole was
stirred at r.t. for 25 min. After evaporation in vacuo, the residue was
dissolved in H2O (5 mL), acidified with 10% HCl and extracted
with Et2O (3 × 20 mL). The organic layer was washed with sat. aq
NaHCO3 (3 × 20 mL) and brine (1 × 10 mL) and dried (MgSO4).
The solvent was evaporated in vacuo and the residue was purified
by CC (n-hexane–EtOAc, 10:1) to give 1f as a pale yellow oil (289
mg, 83%). Spectral data were identical with those in the literature.5
Scheme 5 Proposed mechanism for the ring expansion of 29 to 30
determined from the NOE enhancements (Figure 4). The
alcohols (Z)- and (E)-37 were converted into the corre-
sponding MEM ethers (Z)- and (E)-38 in 81% and 91%
yield, respectively. Irradiation of (E)-38 with UV light
caused it to be partially isomerized to (Z)-38 (41% yield),
with recovery of the starting (E)-38 in 29% yield.
4.1%
3.1%
H
H
TBDPSO
OH
H
TBDPSO
O
H
3.1%
H
OBn H
OH
1-Allyloxy-3-silyloxybenzenes; 1-Allyloxy-3-tert-butyldiphenyl-
silyloxybenzene (1d); Typical Procedure
OBn H 3.0%
H
O
3.2%
4.2%
(Z)-37
(E)-37
TBDPSCl (1.2 mL, 4.52 mmol) was added to a mixture of 1f (507
mg, 3.38 mmol) and imidazole (473 mg, 6.81 mmol) in DMF (5
mL) and the mixture was stirred at r.t. for 20 h. H2O (20 mL) was
added and extracted with Et2O (3 × 60 mL). The organic layer was
washed with H2O (5 × 50 mL) and brine (2 × 40 mL), and then dried
(MgSO4). The solvent was evaporated in vacuo and the residue was
purified by CC (n-hexane–EtOAc, 10:1–5:1) to give 1d as a color-
less oil (1.22 g, 93%).
Figure 4 Selected NOE enhancements of (Z)- and (E)-37
In conclusion, we found that BCl3 was a suitable Lewis
acid for the regioselective CR of resorcinol allyl ethers
1a–d to afford the 6-isomers 2a–d as major products in
good yield and with high regioselectivity (up to 15:1). The
yield and regioselectivity of these reactions depended on
the substituent at the meta position of 1 and the Lewis acid
utilized. CR of the crotyl ether 13 (Z = H) gave the corre-
sponding crotyl resorcinols 15 (Z = H) and 16 (Z = H) in
a ratio of 4:1 under thermal conditions, and in a ratio of
10:1 under Lewis acid conditions. CR of the prenyl ether
13 (Z = CH3) afforded mainly the 4-isomer 21 under ther-
mal conditions, but afforded the 6-isomer 15 (Z = CH3)
under Lewis acid conditions, albeit in low yield. In the
BCl3-mediated CR of the carvonyl ether 10d with a
TBDPS function, the 6-isomer 9d was preferentially
formed with regioselectivity of up to 13:1. The rearranged
product 9d was transformed into the desired MEM ether
(Z)-38 in six steps. Further manipulations aimed at the to-
tal synthesis of miroestrols are under investigation in our
laboratory.
IR (ATR): no characteristic absorption.
1H NMR (400 MHz): d = 1.10 (s, 9 H), 4.29 (d, J = 5.4 Hz, 2 H),
5.17 (dif. dd, J = 10.7, 1.8 Hz, 1 H), 5.26 (dif. dd, J = 17.4, 1.8 Hz,
1 H), 5.91 (ddt, J = 17.4, 10.7, 5.4 Hz, 1 H), 6.35–6.37 (m, 2 H),
6.44 (dif. d, J = 8.8 Hz, 1 H), 6.96 (t, J = 8.8 Hz, 1 H), 7.34–7.43
(m, 6 H), 7.70–7.73 (dif. d, J = 7.2 Hz, 4 H).
13C NMR (100 MHz): d = 19.5, 26.5, 68.6, 106.5, 107.9, 112.4,
117.5, 127.7, 129.4, 129.8, 132.9, 133.2, 135.5, 156.6, 159.4.
HREIMS: m/z [M]+ calcd for C25H28O2Si: 388.1859; found:
388.1835.
1-Allyloxy-3-tert-butyldimethylsilyloxybenzene (1b)
This compound was prepared from 1f in the same manner as for 1d
and was obtained as a colorless oil (86%). Spectral data were iden-
tical with those in the literature.5
1-Allyloxy-3-triisopropylsilyloxybenzene (1c)
This compound was prepared from 1f in the same manner as for 1d
and was obtained as a colorless oil (89%).
All melting points were measured on a micro melting-point hot
stage (Yanaco) and uncorrected. IR spectra were recorded on a JAS-
CO FT/IR-300E spectrophotometer; ATR = attenuated total reflec-
IR (ATR): no characteristic absorption.
1H NMR (400 MHz): d = 1.10 (d, J = 7.2 Hz, 18 H), 1.24 (m, 3 H),
4.50 (ddd, J = 5.2, 1.5, 1.5 Hz, 2 H), 5.28 (ddt, J = 10.5, 1.6, 1.5 Hz,
1
tance system. H NMR spectra were recorded on JEOL JNM-
GSX400A (400 MHz), -ECP400 (400 MHz) or -ECP600 (600
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

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F. Ito et al.
PAPER
1 H), 5.40 (ddt, J = 17.0, 1.6, 1.5 Hz, 1 H), 6.05 (ddt, J = 17.0, 10.5,
5.2 Hz, 1 H), 6.46–6.52 (m, 3 H), 7.09 (dd, J = 8.0, 8.0 Hz, 1 H).
13C NMR (100 MHz): d = 12.7, 17.9, 68.8, 106.9, 107.4, 112.6,
117.6, 129.6, 133.4, 157.2, 159.7.
HREIMS: m/z [M]+ calcd for C18H30O2Si: 306.2015; found:
306.1995.
1H NMR (400 MHz): d = 0.19 (s, 6 H), 0.98 (s, 9 H), 3.34 (d, J = 6.3
Hz, 2 H), 4.89 (s, 1 H, D2O-exch), 5.12–5.17 (m, 2 H), 6.00 (ddt,
J = 17.5, 9.5, 6.3 Hz, 1 H), 6.35 (d, J = 2.3 Hz, 1 H), 6.38 (dd,
J = 8.0, 2.3 Hz, 1 H), 6.92 (d, J = 8.0 Hz, 1 H).
13C NMR (100 MHz): d = –4.5, 18.2, 25.7, 34.6, 107.9, 112.6,
116.2, 118.0, 130.6, 136.8, 154.8, 155.4.
HREIMS: m/z [M]+ calcd for C15H24O2Si: 264.1546; found:
3-(But-2-enyloxyphenoxy)-tert-butyldiphenylsilane (13, Z = H)
This compound was prepared from 12e, crotyl chloride (trans/
cis = 5:1) and TBDPSCl following the procedure for 1f and 1d and
was obtained as a colorless oil (75% in 3 steps, as 5:1 mixture of
trans and cis).
264.1529.
2-Allyl-3-(tert-butyldimethylsilyloxy)phenol (3b)
IR (ATR): 3484 cm–1.
1H NMR (400 MHz): d = 0.22 (s, 6 H), 1.00 (s, 9 H), 3.46 (br d,
J = 6.0 Hz, 2 H), 4.96 (s, 1 H, D2O-exch), 5.08–5.14 (m, 2 H), 5.97
(ddt, J = 17.2, 10.2, 6.0 Hz, 1 H), 6.44 (d, J = 8.0 Hz, 1 H), 6.47 (d,
J = 8.0 Hz, 1 H), 6.97 (dif. dd, J = 8.0, 8.0 Hz, 1 H).
13C NMR (100 MHz): d = –4.2, 18.3, 25.8, 28.1, 109.0, 111.3,
115.6, 116.3, 127.2, 136.2, 154.4, 155.7.
IR (ATR): no characteristic absorption.
1H NMR (400 MHz): d (for trans isomer) = 1.09 (s, 9 H), 1.69 (d,
J = 6.2 Hz, 3 H), 4.20 (dd, J = 6.2, 1.2 Hz, 2 H), 5.56–5.76 (m, 2
H), 6.34–6.36 (m, 2 H), 6.43 (dif. d, J = 8.4 Hz, 1 H), 6.96 (dif. dd,
J = 8.4, 8.4 Hz, 1 H), 7.34–7.44 (m, 6 H), 7.71 (dif. d, J = 6.6 Hz,
4 H).
13C NMR (100 MHz): d = 17.8, 19.5, 26.5, 68.5, 106.4, 107.9,
112.2, 126.0, 127.7, 129.4, 129.8, 130.4, 132.9, 135.5, 156.6, 159.5.
HREIMS: m/z [M]+ calcd for C15H24O2Si: 264.1546; found:
264.1523.
6-Allyl-3-(triisopropylsilyloxy)phenol (2c)
HREIMS: m/z [M]+ calcd for C26H30O2Si: 402.2015; found:
402.2044.
IR (ATR): 3461 cm–1.
1H NMR (400 MHz): d = 1.10 (d, J = 7.3 Hz, 18 H), 1.24 (dif. sept,
J = 7.3 Hz, 3 H), 3.33 (d, J = 6.2 Hz, 2 H), 4.86 (s, 1 H, D2O-exch),
5.13 (m, 2 H), 6.00 (dif. ddt, J = 17.7, 9.5, 6.2 Hz, 1 H), 6.39 (d,
J = 2.2 Hz, 1 H), 6.42 (dd, J = 8.1, 2.2 Hz, 1 H), 6.91 (d, J = 8.1 Hz,
1 H).
13C NMR (100 MHz): d = 12.6, 17.9, 34.5, 107.8, 112.4, 116.1,
117.6, 130.6, 136.9, 154.7, 155.9.
3-(3-Methylbut-2-enyloxyphenoxy)-tert-butyldiphenylsilane
(13, Z = CH3)
This compound was prepared from 12e, 3,3-dimethylallyl bromide,
and TBDPSCl in the same manner as for 13 (Z = H) and was ob-
tained as a colorless oil (84% in 3 steps).
IR (ATR): no characteristic peak.
1H NMR (400 MHz): d = 1.10 (s, 9 H), 1.64 (s, 3 H), 1.74 (s, 3 H),
4.25 (d, 2 H, J = 6.8 Hz), 5.37 (dif. tqq, 1 H, J = 6.8, 1.4, 1.4 Hz),
6.33–6.36 (m, 2 H), 6.44 (dif. d, 1 H, J = 8.0 Hz), 6.96 (dif. dd,
J = 8.0, 8.0 Hz, 1 H), 7.34–7.43 (m, 6 H), 7.71–7.73 (dif. d, J = 6.4
Hz, 4 H).
HREIMS: m/z [M]+ calcd for C18H30O2Si: 306.2015; found:
306.2001.
2-Allyl-3-(triisopropylsilyloxy)phenol (3c)
IR (ATR): 3424 cm–1.
13C NMR (100 MHz): d = 18.1, 19.5, 25.8, 26.5, 64.5, 106.3, 107.9,
1H NMR (400MHz): d = 1.11 (d, J = 7.3 Hz, 18 H), 1.30 (sept,
J = 7.3 Hz, 3 H), 3.50 (ddd, J = 6.4, 1.6, 1.6 Hz, 2 H), 4.94 (s, 1 H,
D2O-exch), 5.07–5.15 (m, 2 H), 5.98 (ddt, J = 17.1, 10.1, 6.4 Hz, 1
H), 6.40 (d, J = 8.0 Hz, 2 H), 6.94 (dif. dd, J = 8.0, 8.0 Hz, 1 H).
13C NMR (100MHz): d = 13.0, 18.1, 28.1, 108.6, 110.8, 115.6,
115.7, 127.1, 136.3, 154.7, 155.6.
112.1, 119.6, 127.7, 129.4, 129.8, 133.0, 135.5, 137.9, 156.6, 159.7.
HREIMS: m/z [M]+ calcd for C27H32O2Si: 416.2172; found:
416.2183.
Microwave-Mediated CR of Allyl Ether 1; Typical Procedure
(Table 1, Entry 1)
HREIMS: m/z [M]+ calcd for C18H30O2Si: 306.2015; found:
A solution of 1a (104 mg, 0.64 mmol) in PhNEt2 (1 mL) was irradi-
ated at 250 °C for 30 min. After cooling to r.t., the mixture was di-
luted with EtOAc (30 mL), washed 10% aq HCl (5 × 10 mL) and
brine (1 × 10 mL), and dried (MgSO4). The solvent was evaporated
in vacuo and the residue was purified by CC (n-hexane–
EtOAc, 20:1 to 10:1) to give 2a (50 mg, 48%) and 3a (34 mg, 32%)
as colorless oils. Spectral data of 2a and 3a were identical with
those reported in the literature.4
306.2011.
6-Allyl-3-(tert-butyldiphenylsilyloxy)phenol (2d)
IR (ATR): 3538 cm–1.
1H NMR (400 MHz): d = 1.08 (s, 9 H), 3.25 (d, J = 6.4 Hz, 2 H),
5.01 (s, 1 H, D2O-exch), 5.06–5.11 (m, 1 H), 5.95 (ddt, J = 17.5,
9.9, 6.3 Hz, 1 H), 6.27–6.30 (m, 2 H), 6.78 (d, J = 8.0 Hz, 1 H),
7.33–7.42 (m, 6 H), 7.70–7.72 (dif. d, J = 7.8 Hz, 4 H).
13C NMR (100 MHz): d = 19.4, 26.5, 34.5, 107.5, 112.3, 116.0,
117.9, 127.7, 129.8, 130.5, 133.0, 135.5, 136.8, 154.5, 155.3.
BCl3-Mediated CR of Allyl Ether 1; Typical Procedure (Table
2, Entry 1)
BCl3 (1 M solution in CH2Cl2, 1.8 mL, 1.8 mmol) was added to a
solution of 15a (104 mg, 0.63 mmol) in CH2Cl2 (1.0 mL) at –50 °C
and the mixture was stirred at –50 °C for 1 h. H2O (10 mL) was add-
ed and the mixture was extracted with CHCl3 (3 × 20 mL). The com-
bined organic layers were washed with brine (1 × 20 mL) and dried
(MgSO4). The solvent was evaporated in vacuo and the residue was
purified by CC (n-hexane–EtOAc, 20:1 to 10:1) to give a colorless
oil 2a (64 mg, 62%), 3a (11 mg, 11%), and 12a (6 mg, 8%).
HREIMS: m/z [M]+ calcd for C25H28O2Si: 388.1859; found:
388.1870.
2-Allyl-3-(tert-butyldiphenylsilyloxy)phenol (3d)
IR (ATR): 3538 cm–1.
1H NMR (400 MHz): d = 1.08 (s, 1 H), 3.66 (d, J = 5.8 Hz, 2 H),
4.92 (s, 1 H, D2O-exch), 5.13–5.19 (m, 2 H), 6.03–6.13 (dif. ddt,
J = 17.0, 10.0, 5.8 Hz, 1 H), 6.05 (dif. d, J = 8.0 Hz, 1 H), 6.38 (d,
J = 8.0 Hz, 1 H), 6.65 (dd, J = 8.0, 8.0 Hz, 1 H), 7.34–7.44 (m, 6
H), 7.71 (dif. d, J = 7.3 Hz, 4 H).
6-Allyl-3-(tert-butyldimethylsilyloxy)phenol (2b)
IR (ATR): 3463 cm–1.
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

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Boron Trichloride Mediated Claisen Rearrangement of Resorcinol Derivatives
1791
13C NMR (100 MHz): d = 19.5, 26.5, 28.1, 108.7, 111.8, 115.5,
115.8, 126.9, 127.8, 129.9, 132.7, 135.4, 136.2, 154.1, 155.3.
HRFABMS: m/z [M + H]+ calcd for C27H32O2Si: 416.2172; found:
416.2141.
HREIMS: m/z [M]+ calcd for C25H28O2Si: 388.1859; found:
388.1885.
6-tert-Butyldiphenylsilyloxy-2,2,3-trimethyl-2,3-dihydrobenzo-
furan (23)
IR (ATR): no characteristic peak.
6-Methoxy-2-methyl-2,3-dihydrobenzofuran (14)
IR (ATR): no characteristic peak.
1H NMR (400 MHz): d = 1.08 (s, 9 H), 1.12 (d, J = 7.2 Hz, 3 H),
1.20 (s, 3 H), 1.40 (s, 3 H), 3.01 (q, J = 7.2 Hz, 1 H), 6.21–6.23 (m,
2 H), 6.74 (d, J = 8.4 Hz, 1 H), 7.33–7.42 (m, 6 H), 7.71 (m, 4 H).
13C NMR (100 MHz): d = 14.7, 19.5, 21.9, 26.5, 27.9, 45.1, 90.2,
102.0, 111.2, 123.5, 125.4, 127.7, 129.7, 133.1, 135.5, 155.8, 158.7.
1H NMR (400 MHz): d = 1.45 (d, J = 6.5 Hz, 1 H), 2.74 (dd,
J = 14.9, 7.3 Hz, 1 H), 3.38 (dd, J = 14.9, 7.8 Hz, 1 H), 3.76 (s, 3
H), 4.93 (dif. qdd, J = 7.8, 7.3, 6.5 Hz, 1 H), 6.36–6.39 (m, 2 H),
7.01 (d, J = 8.1 Hz, 1 H).
13C NMR (100 MHz): d = 21.8, 36.5, 55.5, 80.5, 96.1, 105.6, 118.9,
124.8, 160.3, 160.7.
HRFABMS: m/z [M + H]+ calcd for C27H32O2Si: 416.2172; found:
416.2141.
LRMS-EI: m/z = 160 (M+).
5-tert-Butyldiphenylsilyloxy-2-(1,1-dimethyl)allylphenol (15,
Z = Me)
3-tert-Butyldiphenylsilyloxy-6-(1-methyl)allylphenol (15,
IR (ATR): 3485 cm–1.
Z = H)
IR (ATR): 3537 cm–1.
1H NMR (400 MHz): d = 1.08 (s, 9 H), 1.34 (s, 6 H), 5.24 (dd,
J = 10.6, 1.2 Hz, 1 H), 5.28 (dd, J = 17.7, 1.2 Hz, 1 H), 5.69 (s, 1
H, D2O-exch), 6.13 (dd, J = 17.7, 10.6 Hz, 1 H), 6.26 (dd, J = 8.5,
2.5 Hz, 1 H), 6.34 (d, J = 2.5 Hz, 1 H), 6.91 (d, J = 8.5 Hz, 1 H),
7.34–7.44 (m, 6 H), 7.72 (m, 4 H).
13C NMR (125 MHz): d = 19.4, 26.5, 27.0, 39.7, 109.0, 111.8,
113.1, 126.4, 127.7, 129.8, 133.1, 135.4, 135.5, 148.2, 155.3, 155.5.
1H NMR (400 MHz): d = 1.08 (s, 9 H), 1.30 (d, J = 7.0 Hz, 3 H),
3.53 (qd, J = 7.0, 6.3 Hz, 1 H), 4.89 (s, 1 H, D2O-exch), 5.08–5.13
(m, 2 H), 6.00 (ddd, J = 17.3, 10.4, 6.3 Hz, 1 H), 6.27 (d, J = 2.4
Hz, 1 H), 6.30 (dd, J = 8.4, 2.4 Hz, 1 H), 6.81 (d, J = 8.4 Hz, 1 H),
7.34–7.44 (m, 6 H), 7.71 (dif. d, J = 7.6 Hz, 4 H).
13C NMR (100 MHz): d = 18.8, 19.4, 26.5, 37.0, 107.7, 112.2,
113.9, 122.9, 128.0, 129.8, 133.0, 135.5, 142.8, 154.1, 155.0.
HRFABMS: m/z [M + H]+ calcd for C27H32O2Si : 416.2172; found:
416.2141.
HREIMS: m/z [M]+ calcd for C26H30O2Si: 402.2015; found:
402.2008.
(R)-5-[3-(3-Methoxyphenoxy)prop-1-en-2-yl]-2-methylcyclo-
hex-2-en-1-one (10a); Typical Procedure
3-tert-Butyldiphenylsilyloxy-2-(1-methyl)allylphenol (16,
A mixture of 12a (1.70 mL, 15.5 mmol) and K2CO3 (2.54 g, 18.4
mmol) in DMF (10 mL) was stirred at r.t. for 30 min. 10-Chlorocar-
vone (24; 2.22 g, 12.0 mmol) in DMF (10 mL) was added and the
mixture was stirred at 60 °C for 7 h. After cooling to r.t., sat. aq
NH4Cl (60 mL) and H2O (60 mL) were added and the mixture was
extracted with EtOAc (1 × 50 mL). The combined organic layers
were washed with H2O (5 × 200 mL) and brine (1 × 60 mL), and
dried (MgSO4). The solvent was evaporated in vacuo and the resi-
due purified by CC (hexane–EtOAc, 4: 1) to give 10a as a colorless
oil (2.53 g, 77%); [a]D24 –30.5 (c 1.0, CHCl3).
Z = H)
IR (ATR): 3496 cm–1.
1H NMR (400 MHz): d = 1.48 (d, J = 7.0 Hz, 3 H), 4.49 (dif. qd,
J = 7.0, 4.0 Hz, 1 H), 5.37–5.45 (m, 2 H), 5.64 (1 H, s, D2O-exch),
6.05 (d, J = 8.4 Hz, 1 H), 6.33–6.41 (dif. ddd, J = 18.5, 11.6, 4.0
Hz, 1 H), 6.36 (dif. d, J = 8.0 Hz, 1 H), 6.65 (dif. dd, J = 8.0, 8.0
Hz, 1 H), 7.35–7.43 (m, 6 H), 7.71 (dif. dd, J = 6.4, 6.4 Hz, 4 H).
13C NMR (100 MHz): d = 16.3, 19.5, 26.5, 32.5, 110.1, 111.6,
115.4, 119.9, 127.2, 127.8, 129.9, 132.5, 132.6, 135.4, 142.7, 153.2,
156.2.
IR (neat): 1672 cm–1.
HREIMS: m/z [M]+ calcd for C26H30O2Si: 402.2015; found:
402.1993.
1H NMR (400 MHz): d = 1.79 (ddd, J = 2.6, 1.5, 1.5 Hz, 3 H), 2.38
(dddq, J = 18.1, 10.8, 2.6, 2.6 Hz, 1 H), 2.45 (dd, J = 16.1, 13.2 Hz,
1 H), 2.56 (ddddq, J = 18.1, 5.9, 4.4, 1.5, 1.5 Hz, 1 H), 2.68 (ddd,
J = 16.1, 3.8, 1.5 Hz, 1 H), 2.93 (m, 1 H), 3.79 (s, 3 H), 4.52, 4.49
(d each, J = 12.6 Hz, 1 H), 5.09, 5.27 (s each, 1 H), 6.47 (t, J = 2.4
Hz, 1 H), 6.50 (dd, J = 8.0, 2.4 Hz, 1 H), 6.52 (dd, J = 8.0, 2.4 Hz,
1 H), 6.76 (ddq, J = 5.7, 2.6, 1.5 Hz, 1 H), 7.17 (t, J = 8.0 Hz, 1 H).
13C NMR (100 MHz): d = 15.7, 31.4, 38.3, 43.1, 55.2, 69.9, 101.2,
106.6, 106.8, 113.3, 129.9, 135.5, 144.3, 146.2, 159.7, 160.8, 199.3.
HRFABMS: m/z [M + H]+ calcd for C17H21O3: 273.1491; found:
273.1502.
3-tert-Butyldiphenylsilyloxy-4-(3,3-dimethyl)allylphenol (21)
IR (ATR): 3373 cm–1.
1H NMR (400 MHz): d = 1.09 (s, 9 H), 1.72 (s, 3 H), 1.76 (s, 3 H),
3.42 (d, J = 7.2 Hz, 2 H), 4.39 (s, 1 H, D2O-exch), 5.40 (dif. dqq,
J = 7.2, 1.4, 1.4 Hz, 1 H), 5.91 (d, J = 2.4 Hz, 1 H), 6.27 (dd,
J = 8.2, 2.4 Hz, 1 H), 6.96 (d, J = 8.2 Hz, 1 H), 7.33–7.42 (m, 6 H),
7.71 (dif. d, J = 8.0 Hz, 4 H).
13C NMR (100 MHz): d = 17.9, 19.5, 25.8, 26.4, 28.2, 106.4, 107.8,
123.2, 124.1, 127.8, 129.9, 132.3, 132.2, 132.7, 135.4, 153.8, 153.8.
HRFABMS: m/z [M + H]+ calcd for C27H32O2Si: 416.2172; found:
416.2141.
(R)-5-[3-(3-Benzoyloxyphenoxy)prop-1-en-2-yl]-2-methylcyclo-
hex-2-en-1-one (10e) and (R)-5-[3-(3-Hydroxyphenoxy)prop-1-
en-2-yl]-2-methylcyclohex-2-en-1-one (10f)
Compounds 10e and 10f were prepared from 12e and 24 by the
same procedure as for 10a and were obtained as a colorless oil in
40% (for 10e) and as colorless minute crystals in 18% (for 10f). Hy-
drolysis of crude product in this reaction gave 10f in 70% yield.
5-(tert-Butyldiphenylsilyloxy)-2-(1,2-dimethylallyl)phenol (22)
IR (ATR): 3464 cm–1.
1H NMR (400 MHz): d = 1.08 (s, 9 H), 1.33 (d, J = 7.2 Hz, 3 H),
1.59 (s, 3 H), 3.43 (q, J = 7.2 Hz, 1 H), 4.94 (s, 1 H), 5.00 (s, 1 H),
5.28 (s, 1 H, D2O-exch), 6.26–6.29 (m, 2 H), 6.79 (d, J = 8.1 Hz, 1
H), 7.34–7.43 (m, 6 H), 7.70 (dif. d, J = 6.8 Hz, 4 H).
13C NMR (100 MHz): d = 18.4, 19.4, 20.6, 26.5, 41.6, 107.9, 111.0,
112.1, 122.1, 127.7, 128.5, 129.6, 133.0, 135.5, 150.3, 155.0, 155.2.
10e
[a]D24 –19.4 (c 1.0, CHCl3).
IR (neat): 1735, 1671 cm–1.
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

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PAPER
(R)-5-[3-(2-Hydroxy-4-methoxyphenyl)prop-1-en-2-yl]-2-
1H NMR (400 MHz): d = 1.79 (ddd, J = 2.7, 1.4, 1.4 Hz, 3 H), 2.37
(dddq, J = 18.1, 10.4, 2.8, 2.8 Hz, 1 H), 2.46 (dd, J = 16.1, 13.1 Hz,
1 H), 2.57 (ddddq, J = 18.1, 5.9, 4.6, 1.4, 1.4 Hz, 1 H), 2.69 (ddd,
J = 16.1, 3.8, 1.4 Hz, 1 H), 2.90–2.98 (m, 1 H), 4.52, 4.55 (d each,
J = 12.4 Hz, 1 H), 5.10 (s, 1 H), 5.28 (s, 1 H), 6.76 (ddq, J = 5.9,
2.7, 1.4 Hz, 1 H), 6.80 (t, J = 2.3 Hz, 1 H), 6.82–6.85 (m, 2 H), 7.32
(t, J = 8.2 Hz, 1 H), 7.52 (dif. t, J = 7.8 Hz, 2 H), 7.65 (dif. t, J = 7.7
Hz, 1 H), 8.20 (dif. dd, J = 8.3, 1.5 Hz, 2 H).
13C NMR (100 MHz): d = 15.7, 31.4, 38.3, 43.0, 70.2, 108.5, 112.4,
113.6, 114.3, 128.6, 129.4, 129.9, 130.1, 133.6, 135.6, 144.3, 145.8,
151.8, 159.4, 165.0, 199.2.
HRFABMS: m/z [M + H]+ calcd for C23H23O4: 363.1596; found:
363.1607.
methylcyclohex-2-en-1-one (9a)
Mp 109–110 °C; [a]D24 –3.8 (c 1.0, CHCl3).
IR (Nujol): 3209, 1649 cm–1.
1H NMR (400 MHz): d = 1.77 (ddd, J = 2.4, 1.5, 1.5 Hz, 3 H), 2.32
(dddq, J = 18.1, 10.8, 2.6, 2.6 Hz, 1 H), 2.39 (dd, J = 16.3, 13.5 Hz,
1 H), 2.49 (ddddq, J = 18.1, 5.8, 4.2, 1.5, 1.5 Hz, 1 H), 2.63–2.72
(m, 2 H), 3.38 (s, 2 H), 3.76 (s, 3 H), 4.93, 4.95 (s each, 1 H), 5.49
(br s, 1 H), 6.40 (d, J = 2.4 Hz, 1 H), 6.44 (dd, J = 8.2, 2.4 Hz, 1 H),
6.73 (ddq, J = 5.8, 2.4, 1.5 Hz, 1 H), 6.97 (d, J = 8.2 Hz, 1 H).
13C NMR (100 MHz): d = 15.7, 31.6, 35.6, 40.1, 43.3, 55.3, 102.1,
106.2, 111.4, 116.9, 131.4, 135.4, 144.9, 150.3, 155.2, 159.6, 200.0.
EIMS: m/z (%) = 273 (5.4), 272 (M+, 29.2), 163 (25.0), 148 (70.4),
137 (100.0), 135 (23.8), 124 (20.3).
10f
Mp 50–51 °C; [a]D24 –25.0 (c 1.0, CHCl3).
Anal. Calcd for C17H20O3: C, 74.97; H, 7.40. Found: C, 74.88; H,
7.39.
IR (neat): 3371, 1655 cm–1.
1H NMR (400 MHz): d = 1.79 (ddd, J = 2.7, 1.5, 1.5 Hz, 3 H), 2.37
(dddq, J = 18.3, 10.5, 2.7, 2.7 Hz, 1 H), 2.45 (dd, J = 16.1, 13.0 Hz,
1 H), 2.56 (ddddq, J = 18.3, 5.9, 4.4, 1.5, 1.5 Hz, 1 H), 2.69 (ddd,
J = 16.1, 3.8, 1.5 Hz, 1 H), 2.89–2.97 (m, 1 H), 4.48, 4.51 (d each,
J = 12.7 Hz, 1 H), 5.09 (s, 1H), 5.18 (br s, 1 H), 5.26 (s, 1 H), 6.41
(t, J = 2.4 Hz, 1 H), 6.44 (ddd, J = 8.2, 2.4, 0.8 Hz, 1 H), 6.48 (ddd,
J = 8.2, 2.4, 0.8 Hz, 1 H), 6.77 (ddq, J = 5.8, 2.7, 1.5 Hz, 1 H), 7.12
(t, J = 8.2 Hz, 1 H).
13C NMR (100 MHz): d = 15.7, 31.4, 38.3, 43.0, 69.9, 102.3, 106.7,
108.3, 113.5, 130.1, 135.5, 145.3, 146.0, 157.1, 159.7, 200.2.
HRFABMS: m/z [M + H]+ calcd for C16H19O3: 259.1334; found:
259.1341.
(R)-5-[3-(6-Hydroxy-2-methoxyphenyl)prop-1-en-2-yl]-2-
methylcyclohex-2-en-1-one (25a)
Mp 104–105 °C; [a]D24 –12.0 (c 1.0, CHCl3).
IR (Nujol): 3247, 1646 cm–1.
1H NMR (400 MHz): d = 1.78 (ddd, J = 2.5, 1.4, 1.4 Hz, 3 H), 2.37
(dddq, J = 18.2, 10.6, 2.6, 2.6 Hz, 1 H), 2.39 (dd, J = 16.5, 13.7 Hz,
1 H), 2.49 (ddddq, J = 18.2, 5.8, 4.4, 1.4, 1.4 Hz, 1 H), 2.69–2.76
(m, 2 H), 3.47 (s, 2 H), 3.79 (s, 3 H), 4.83, 4.87 (s each, 1 H), 5.30
(br s, 1 H), 6.48 (dd, J = 8.1, 2.0 Hz, 2 H), 6.73 (ddq, J = 5.8, 2.5,
1.4 Hz, 1 H), 7.08 (t, J = 8.1 Hz, 1 H).
13C NMR (100 MHz): d = 15.7, 28.6, 31.6, 40.7, 43.4, 55.8, 103.3,
108.8, 110.1, 113.4, 127.8, 135.4, 145.0, 150.0, 155.5, 158.4, 200.1.
EIMS: m/z (%) = 273 (7.2), 272 (M+, 38.5), 163 (38.2), 148 (62.3),
137 (100.0), 135 (82.2), 124 (13.9).
Anal. Calcd for C16H18O3: C, 74.40; H, 7.02; N, 0.00. Found: C,
74.23; H, 6.85; N, 0.25.
(R)-5-[3-(3-Isopropoxyphenoxy)prop-1-en-2-yl]-2-methylcyclo-
hex-2-en-1-one (10g)
Anal. Calcd for C17H20O3: C, 74.97; H, 7.40. Found: C, 74.90; H,
7.20.
A mixture of phenol 10f (300 mg, 1.16 mmol), K2CO3 (567 mg,
4.09 mmol) and 2-bromopropane (0.33 mL, 3.51 mmol) in DMF
(1.5 mL) was stirred at 50 °C for 4 h. After cooling to r.t., 10% aq
HCl (2 mL) and H2O (2 mL) were added and extracted with Et2O (2
× 20 mL). The combined organic layers were washed with H2O (5
× 30 mL) and brine (1 × 20 mL), and dried (MgSO4). The solvent
was evaporated in vacuo and the residue was purified by CC (hex-
ane–EtOAc, 10:1) to give 10g as a colorless oil (298 mg, 85%);
[a]D24 –28.4 (c 1.0, CHCl3).
(R)-5-[3-(2,4-Dihydroxyphenyl)prop-1-en-2-yl]-2-methylcyclo-
hex-2-en-1-one (9f)
Mp 122–125 °C; [a]D24 +0.4 (c 1.0, MeOH).
IR (ATR): 3349, 1655 cm–1.
1H NMR (400 MHz): d = 1.76 (ddd, J = 2.6, 1.4, 1.4 Hz, 3 H), 2.27–
2.38 (m, 1 H), 2.38 (dd, J = 16.5, 13.6 Hz, 1 H), 2.48 (dif. ddd,
J = 18.3, 5.8, 4.4 Hz, 1 H), 2.63–2.72 (m, 2 H), 3.33, 3.38 (d each,
J = 16.0 Hz, 1 H), 4.92, 4.94 (s each, 1 H), 5.64 (br s, 2 H), 6.35 (d,
J = 2.7 Hz, 1 H), 6.37 (dd, J = 8.1, 2.7 Hz, 1 H), 6.75 (ddq, J = 5.8,
2.6, 1.4 Hz, 1 H), 6.90 (d, J = 8.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3 + CD3OD): d = 15.4, 31.6, 34.1, 40.2,
43.2, 102.4, 106.8, 110.5, 116.8, 131.0, 134.9, 146.0, 150.4, 155.3,
155.8, 201.2.
IR (neat): 1675 cm–1.
1H NMR (400 MHz): d = 1.33 (d, J = 6.0 Hz, 1 H), 1.79 (ddd,
J = 2.6, 1.5, 1.5 Hz, 3 H), 2.36 (dddq, J = 18.1, 10.8, 2.6, 2.6 Hz, 1
H), 2.45 (dd, J = 16.1, 13.2 Hz, 1 H), 2.56 (ddddq, J = 18.1, 5.9,
4.4, 1.5, 1.5 Hz, 1 H), 2.68 (ddd, J = 16.1, 3.8, 1.5 Hz, 1 H), 2.89–
2.97 (m, 1 H), 4.48, 4.51 (d each, J = 12.3 Hz, 1 H), 4.52 (sept,
J = 6.0 Hz, 1 H), 5.08, 5.26 (s each, 1 H), 6.45 (t, J = 2.2 Hz, 1 H),
6.47 (dd, J = 8.3, 2.2 Hz, 1 H), 6.50 (dd, J = 8.3, 2.2 Hz, 1 H), 6.75
(ddq, J = 5.9, 2.6, 1.5 Hz, 1 H), 7.15 (t, J = 8.3 Hz, 1 H).
HREIMS: m/z [M]+ calcd for C16H18O3: 258.1256; found: 258.1233.
(R)-5-[3-(2,6-Dihydroxyphenyl)prop-1-en-2-yl]-2-methylcyclo-
hex-2-en-1-one (25f)
13C NMR (100 MHz): d = 15.6, 22.0, 31.4, 38.3, 43.0, 69.8, 69.9,
102.9, 106.6, 108.3, 113.2, 129.8, 135.5, 144.3, 146.2, 159.0, 159.7,
199.2.
Mp 40–45 °C; [a]D22 –13.5 (c 0.45, CH3OH).
IR (ATR): 3352, 1647 cm–1.
1H NMR (400 MHz): d = 1.77 (ddd, J = 2.7, 1.4, 1.4 Hz, 3 H), 2.32–
2.44 (m, 2 H), 2.54 (ddddq, J = 18.1, 5.9, 4.5, 1.4, 1.4 Hz, 1 H),
2.67–2.80 (m, 2 H), 3.49, 3.58 (d each, J = 15.8 Hz, 1 H), 4.96, 4.99
(s each, 1 H), 5.43 (br s, 2 H), 6.42 (d, J = 8.1 Hz, 2 H), 6.76 (ddq,
J = 5.9, 2.7, 1.4 Hz, 1 H), 6.97 (t, J = 8.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3 + CD3OD): d = 15.2, 27.9, 31.4, 40.8,
43.1, 106.6, 108.8, 112.6, 126.9, 134.7, 146.5, 149.5, 155.9, 201.6.
HRFABMS: m/z [M + H]+ calcd for C19H25O3: 301.1804; found:
301.1776.
BCl3-Mediated Claisen Rearrangement of 10a, 10e, 10f and 10g
These reactions were performed by the same procedure as that used
for 1a (Table 2, entry 1).
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

PAPER
Boron Trichloride Mediated Claisen Rearrangement of Resorcinol Derivatives
1793
HREIMS: m/z [M]+ calcd for C16H18O3: 258.1256; found: 258.1250.
13.4 Hz, 1 H), 2.56 (ddddq, J = 18.1, 5.8, 4.2, 1.4, 1.4 Hz, 1 H),
2.67–2.76 (m, 2 H), 3.48 (s, 2 H), 4.52 (sept, J = 6.0 Hz, 1 H), 4.86
(s, 1 H), 4.87 (br s, 1 H), 5.37 (br s, 1 H), 6.44 (d, J = 8.2 Hz, 1 H),
6.47 (d, J = 8.2 Hz, 1 H), 6.75 (ddq, J = 5.8, 2.5, 1.4 Hz, 1 H), 7.04
(t, J = 8.2 Hz, 1 H).
(R)-5-[3-(4-Benzoyloxy-2-hydroxyphenyl)prop-1-en-2-yl]-2-
methylcyclohex-2-en-1-one (9e)
Mp 149–150 °C; [a]D25 +0.9 (c 0.84, CHCl3).
IR (Nujol): 3209, 1729, 1648 cm–1.
13C NMR (100 MHz): d = 15.7, 22.10, 22.14, 28.8, 31.6, 40.4, 43.3,
70.0, 105.4, 108.3, 110.1, 114.3, 127.5, 135.3, 145.0, 150.1, 155.8,
156.6, 200.1.
EIMS: m/z (%) = 301 (5.4), 300 (M+, 25.5), 165 (95.8), 149 (62.1),
135 (100.0), 123 (79.4), 109 (28.3).
1H NMR (400 MHz): d = 1.78 (ddd, J = 2.4, 1.4, 1.4 Hz, 3 H), 2.30–
2.40 (m, 1 H), 2.43 (dd, J = 16.1, 13.4 Hz, 1 H), 2.47–2.54 (m, 1 H),
2.66–2.76 (m, 2 H), 3.41, 3.45 (d each, J = 16.1 Hz, 1 H), 4.93, 4.98
(s each, 1 H), 5.77 (br s, 1 H), 6.72–6.76 (m, 3 H), 7.12 (d, J = 7.9
Hz, 1 H), 7.50 (dif. t, J = 7.7 Hz, 2 H), 7.63 (dif. t, J = 7.5 Hz, 1 H),
8.18 (dif. dd, J = 8.4, 1.3 Hz, 2 H).
13C NMR (100 MHz): d = 15.6, 31.5, 35.0, 40.2, 43.2, 109.4, 111.5,
113.3, 123.0, 128.5, 129.4, 130.1, 131.1, 133.6, 135.3, 145.4, 149.7,
150.1, 155.0, 165.4, 200.5.
Anal. Calcd for C19H24O3: C, 75.97; H, 8.05. Found: C, 76.21; H,
8.11.
BCl3-Mediated Claisen Rearrangement of 10d via Introduction
of TBDPS Group to Phenol 10f
To a solution of 10f (302 mg, 1.17 mmol), imidazole (162 mg, 2.37
mmol) in DMF (1.5 mL), was added TBDPSCl (0.40 mL, 1.54
mmol) at r.t. and the mixture was stirred at r.t. for 4.5 h. H2O (50
mL) was added and the mixture was extracted with Et2O (2 × 100
mL). The combined organic layers were washed with H2O (3 × 100
mL) and brine (1 × 100 mL), and dried (MgSO4). The solvent was
evaporated in vacuo. The crude 10d was dissolved in CH2Cl2 (6
mL) and 1 M solution of BCl3 (3.5 mL, 3.5 mmol) was added at
–50 °C. The mixture was stirred at –50 °C for 1 h. H2O (80 mL) was
added and the mixture was extracted with CHCl3 (2 × 100 mL). The
combined organic layers were washed with H2O (1 × 100 mL) and
brine (1 × 100 mL), and dried (MgSO4). The solvent was evaporated
in vacuo and the residue was purified by flash CC (n-hexane–
EtOAc, 98:2–90:10) to give 9d (439 mg, 76%) and 25d (35 mg,
6%).
EIMS: m/z (%) = 362 (M+, 13.0), 105 (100.0), 77 (24.0).
Anal. Calcd for C23H22O4: C, 76.22; H, 6.12. Found: C, 75.94; H,
5.97.
(R)-5-[3-(2-Benzoyloxy-6-hydroxyphenyl)-prop-1-en-2-yl]-2-
methylcyclohex-2-en-1-one (25e)
Mp 145–146 °C; [a]D25 –19.6 (c 0.17, CHCl3)
IR (Nujol): 3169, 1722, 1636 cm–1.
1H NMR (400 MHz): d = 1.75 (ddd, J = 2.7, 1.5, 1.5 Hz, 3 H), 2.24
(dddq, J = 18.2, 10.4, 2.7, 2.7 Hz, 1 H), 2.32 (dd, J = 16.1, 13.4 Hz,
1 H), 2.37–2.46 (m, 1 H), 2.63–2.71 (m, 2 H), 3.38, 3.45 (d each,
J = 15.8 Hz, 1 H), 4.75, 4.81 (s each, 1 H), 5.95 (br s, 1 H), 6.66 (br
d, J = 5.9 Hz, 1 H), 6.76 (dif. d, J = 8.1 Hz, 2 H), 7.17 (t, J = 8.1
Hz, 1 H), 7.52 (dif. t, J = 7.7 Hz, 2 H), 7.65 (dif. t, J = 7.6 Hz, 1 H),
8.18 (dif. dd, J = 8.4, 1.3 Hz, 2 H).
13C NMR (100 MHz): d = 15.6, 29.5, 31.5, 40.4, 43.2, 110.7, 113.4,
114.6, 118.4, 127.6, 128.6, 129.3, 130.1, 133.7, 135.2, 145.4, 148.5,
150.5, 155.6, 165.2, 200.5.
(R)-5-{3-[4-(tert-Butyldiphenylsilyloxy)-2-hydroxyphe-
nyl]prop-1-en-2-yl}-2-methylcyclohex-2-en-1-one (9d)
Mp 141–142 °C; [a]D25 –1.7 (c 1.0, CHCl3).
IR (Nujol): 3372, 1648 cm–1.
1H NMR (400 MHz): d = 1.08 (s, 9 H), 1.76 (ddd, J = 2.5, 1.4, 1.4
Hz, 3 H), 2.25 (dddq, J = 18.2, 10.4, 2.5, 2.5 Hz, 1 H), 2.34 (dd,
J = 16.1, 13.3 Hz, 1 H), 2.42 (dif. ddd, J = 18.2, 7.3, 5.8 Hz, 1 H),
2.59 (ddd, J = 16.1, 3.7, 1.4 Hz, 1 H), 2.62–2.68 (m, 1 H), 3.28 (s,
2 H), 4.84, 4.90 (s each, 1 H), 4.93 (s, 1 H), 6.25 (d, J = 2.4 Hz, 1
H), 6.29 (d, J = 8.2, 2.4 Hz, 1 H), 6.70 (ddq, J = 5.8, 2.8, 1.4 Hz, 1
H), 6.76 (d, J = 8.2 Hz, 1 H), 7.33–7.43 (m, 6 H), 7.70 (dif. dd,
J = 8.0, 1.5 Hz, 4 H).
13C NMR (100 MHz): d = 15.6, 19.4, 26.4, 31.5, 35.0, 40.1, 43.1,
107.5, 111.0, 112.0, 117.6, 127.6, 129.8, 130.8, 132.9, 135.2, 135.4,
145.3, 150.1, 154.7, 155.2, 200.3.
EIMS: m/z (%) = 497 (42.5), 496 (M+, 98.6), 440 (91.2), 439
(100.0), 361 (91.6), 291 (71.7), 199 (62.8).
HRFABMS: m/z [M + H]+ calcd for C23H23O4: 363.1596; found:
363.1611.
(R)-5-[3-(2-Hydroxy-4-isopropoxyphenyl)prop-1-en-2-yl]-2-
methylcyclohex-2-en-1-one (9g)
Mp 78–79 °C; [a]D24 –1.2 (c 1.1, CHCl3).
IR (ATR): 3332, 1647 cm–1.
1H NMR (400 MHz): d = 1.31 (d, J = 6.0 Hz, 6 H), 1.77 (ddd,
J = 2.5, 1.4, 1.4 Hz, 3 H), 2.27–2.36 (m, 1 H), 2.39 (dd, J = 16.3,
13.5 Hz, 1 H), 2.48 (ddddq, J = 18.1, 5.7, 4.6, 1.4, 1.4 Hz, 1 H),
2.63–2.74 (m, 2 H), 3.37 (s, 2 H), 4.47 (sept, J = 6.0 Hz, 1 H), 4.93,
4.95 (s each, 1 H), 5.49 (br s, 1 H), 6.39 (d, J = 2.5 Hz, 1 H), 6.42
(dd, J = 8.2, 2.5 Hz, 1 H), 6.73 (ddq, J = 5.7, 2.5, 1.4 Hz, 1 H), 6.94
(d, J = 8.2 Hz, 1 H).
13C NMR (100 MHz): d = 15.7, 22.1, 31.6, 35.6, 40.0, 43.3, 69.9,
103.8, 108.1, 111.3, 116.6, 131.3, 135.4, 144.8, 150.3, 155.2, 157.9,
199.9.
Anal. Calcd for C32H36O3Si: C, 77.38; H, 7.31. Found: C, 77.56; H,
7.27.
(R)-5-{3-[2-(tert-Butyldiphenylsilyloxy)-6-hydroxyphe-
nyl]prop-1-en-2-yl}-2-methylcyclohex-2-en-1-one (25d)
Mp 156–157 °C; [a]D25 –6.6 (c 0.56, CHCl3).
HRFABMS: m/z [M]+ calcd for C19H25O3: 301.1804; found:
301.1800.
IR (Nujol): 3280, 1636 cm–1.
Anal. Calcd for C19H24O3: C, 75.97; H, 8.05. Found: C, 75.84; H,
7.98.
1H NMR (400 MHz): d = 1.06 (s, 9 H), 1.79 (ddd, J = 2.7, 1.4, 1.4
Hz, 3 H), 2.39 (dddq, J = 18.1, 10.5, 2.7, 2.7 Hz, 1 H), 2.49 (dd,
J = 16.1, 13.4 Hz, 1 H), 2.60 (dif. ddd, J = 18.1, 5.9, 4.6 Hz, 1 H),
2.72 (ddd, J = 16.1, 3.7, 1.4 Hz, 1 H), 2.81–2.90 (m, 1 H), 3.63, 3.68
(d each, J = 16.1 Hz, 1 H), 4.84, 4.96 (s each, 1 H), 5.33 (br s, 1 H),
6.05, 6.38 (d each, J = 8.1 Hz, 1 H), 6.66 (t, J = 8.1 Hz, 1 H), 6.73
(ddq, J = 5.9, 2.7, 1.4 Hz, 1 H), 7.33–7.45 (m, 6 H), 7.69 (dif. dd,
J = 8.0, 1.4 Hz, 4 H).
(R)-5-[3-(6-Hydroxy-2-isopropoxyphenyl)prop-1-en-2-yl]-2-
methylcyclohex-2-en-1-one (25g)
Mp 80–81 °C; [a]D22 –8.2 (c 0.30, CHCl3).
IR (ATR): 3259, 1647 cm–1.
1H NMR (400 MHz): d = 1.30 (d, J = 6.0 Hz, 6 H), 1.77 (ddd,
J = 2.5, 1.4, 1.4 Hz, 3 H), 2.29–2.38 (m, 1 H), 2.40 (dd, J = 16.1,
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

1794
F. Ito et al.
PAPER
13C NMR (100 MHz): d = 15.7, 19.4, 26.5, 29.3, 31.9, 41.3, 43.4,
108.7, 110.0, 111.6, 115.3, 127.0, 127.8, 129.9, 132.4, 132.5, 135.3,
135.4, 145.0, 149.4, 154.3, 155.6, 200.1.
HRFABMS: m/z [M + H]+ calcd for C32H36O3Si: 497.2512; found:
497.2469
brine (1 × 20 mL), and dried (MgSO4). The solvent was evaporated
in vacuo and the residue was purified by CC (n-hexane–
EtOAc, 8:1) to give 29 as a 1:1 mixture of diastereoisomers (211
mg, 67%); colorless oil .
IR (neat): 1675 cm–1.
1H NMR (400 MHz): d = 1.09, 1.10 (s each, 9 H), 1.73 (br s, 6 H),
2.07–2.34 (m, 9 H), 2.35, 2.36 (d each, J = 4.6 Hz, 1 H), 2.49 (d,
J = 4.6 Hz, 1 H), 2.52 (d, J = 12.6 Hz, 1 H), 2.54 (d, J = 4.6 Hz, 1
H), 2.56 (d, J = 14.5 Hz, 1 H), 2.69 (d, J = 14.5 Hz, 1 H), 2.98, 3.09
(d each, J = 14.5 Hz, 1 H), 4.60 (d, J = 11.7 Hz, 1 H), 4.64 (s, 2 H),
4.65 (d, J = 11.7 Hz, 1 H), 6.30, 6.31 (d each, J = 2.3 Hz, 1 H), 6.33
(dd, J = 8.1, 2.3 Hz, 2 H), 6.52, 6.56 (dif. d each, J = 5.4 Hz, 1 H),
6.83, 6.85 (d each, J = 8.1 Hz, 1 H), 7.21–7.24 (m, 4 H), 7.29–7.44
(m, 18 H), 7.67–7.71 (m, 8 H).
13C NMR (100 MHz): d = 15.6, 19.4, 26.5, 27.6, 27.9, 31.9, 32.5,
37.8, 39.1, 39.7, 50.5, 60.3, 60.6, 69.9, 104.3, 111.8, 117.1, 117.2,
127.5, 127.7, 127.7, 128.0, 128.5, 129.9, 131.4, 131.5, 132.9, 135.0,
135.3, 135.5, 136.6, 136.7, 144.2, 144.5, 155.6, 157.1, 199.1.
(R)-5-[3-(2-Benzoyloxy-4-tert-Butyldiphenylsilyloxyphe-
nyl)prop-1-en-2-yl]-2-methylcyclohex-2-en-1-one (26)
A mixture of 9d (714 mg, 1.44 mmol), KI (120 mg, 0.72 mmol),
K2CO3 (320 mg, 2.32 mmol) and benzyl bromide (0.26 mL, 2.19
mmol) in DMF (3 mL) was stirred at r.t. for 3 h. Sat. aq NH4Cl (20
mL) was added and the mixture was extracted with EtOAc (3 × 30
mL). The combined organic layers were washed with H2O (5 × 90
mL) and brine (1 × 30 mL), and dried (MgSO4). The solvent was
evaporated in vacuo and the residue was purified by CC (n-hexane–
Et2O, 9:1) to give 26 as a colorless oil (797 mg, 94%); [a]D23 –1.3
(c 1.0, CHCl3).
IR (neat): 1673 cm–1.
1H NMR (400 MHz): d = 1.09 (s, 9 H), 1.75 (ddd, J = 2.7, 1.4, 1.4
Hz, 3 H), 2.15 (dddq, J = 18.3, 10.5, 2.6, 2.6 Hz, 1 H), 2.31 (dd,
J = 16.0, 13.4 Hz, 1 H), 2.23–2.39 (m, 1 H), 2.52 (ddd, J = 16.0,
3.7, 1.4 Hz, 1 H), 2.56–2.64 (m, 1 H), 3.22, 3.28 (d each, J = 15.6
Hz, 1 H), 4.63 (s, 1 H), 4.65 (s, 2 H), 4.77 (s, 1 H), 6.31 (d, J = 2.3
Hz, 1 H), 6.33 (dd, J = 8.1, 2.3 Hz, 1 H), 6.59 (ddq, J = 5.7, 2.7, 1.4
Hz, 1 H), 6.80 (d, J = 8.1 Hz, 1 H), 7.21 (dif. dd, J = 7.5, 2.0 Hz, 2
H), 7.27–7.44 (m, 9 H), 7.70 (dif. dd, J = 8.1, 1.5 Hz, 4 H).
13C NMR (100 MHz): d = 15.7, 19.4, 26.6, 31.8, 34.3, 40.6, 43.4,
69.8, 104.6, 110.3, 111.8, 120.4, 127.3, 127.7, 128.3, 129.8, 130.5,
133.0, 134.8, 135.1, 135.6, 137.0, 144.8, 150.4, 155.1, 156.7, 200.0.
HREIMS: m/z [M]+ calcd for C39H42O3Si: 586.2903; found:
586.2874.
HREIMS: m/z [M]+ calcd for C39H42O4Si: 602.2852; found:
602.2856.
6-[2-Benzyloxy-4-(tert-butyldiphenylsilyloxy)benzyl]-6-
hydroxymethyl-2-methylcyclohepta-2,4-dienone (30)
To a solution of 29 (105 mg, 0.17 mmol) in CH2Cl2 (1 mL), were
added Et3N (0.12 mL, 0.86 mmol) and TMSOTf (0.09 mL, 0.50
mmol) at 0 °C and the mixture was stirred at 0 °C for 30 min. The
mixture was diluted with EtOAc (30 mL) and washed with H2O (4
× 20 mL) and brine (1 × 20 mL), and dried (MgSO4). The solvent
was evaporated in vacuo and the residue was purified by CC (Al2O3,
n-hexane–EtOAc, 20: 1) to give crude 34 (61 mg), which was treat-
ed with TsOH·H2O (3.3 mg, 17 mmol) in MeOH (3 mL) and the
mixture was stirred at r.t. for 30 min. NaHCO3 (27 mg, 0.32 mmol)
was added and the mixture was stirred at r.t. for 30 min, and then
filtered. The solvent was evaporated in vacuo and the residue was
purified by CC (n-hexane–EtOAc, 3:1) to give 30 as a colorless oil
(50 mg, 47%).
(R)-5-[3-(2-Benzyloxy-4-tert-butyldimethylsilyloxy-5-chloro-
phenyl)prop-1-en-2-yl]-2-methylcyclohex-2-en-1-one (27)
A solution of 26 (105 mg, 0.18 mmol) in CH2Cl2 (2 mL), and SiO2
(33 mg) were added to a suspension of Ca(OCl)2 (60%, 44 mg, 0.18
mmol) in H2O (0.2 mL) and the mixture was stirred at r.t. for 5 h.
The mixture was filtered and the filtrate was dried (MgSO4). The
solvent was evaporated in vacuo and the residue was purified by
flash CC (n-hexane–Et2O, 100:1 to 90:10) to give 27 as a colorless
oil (54 mg, 48%); [a]D21 +1.3 (c 1.0, CHCl3).
IR (ATR): 3503, 1652, 1604 cm–1.
1H NMR (400 MHz): d = 1.10 (s, 9 H), 1.93 (s, 3 H), 2.55 (d,
J = 13.7 Hz, 1 H), 2.62 (d, J = 13.7 Hz, 1 H), 2.65 (d, J = 13.7 Hz,
1 H), 2.79 (d, J = 13.7 Hz, 1 H), 2.82 (dd, J = 8.2, 7.1 Hz, 1 H, D2O-
exch), 3.10 (dd, J = 11.7, 8.2 Hz, 1 H; d, J = 11.6 Hz with added
D2O), 3.20 (dd, J = 11.7, 7.1 Hz, 1 H; d, J = 11.6 Hz with added
D2O), 4.63, 4.66 (d each, J = 11.6 Hz, 1 H), 5.76 (d, J = 11.8 Hz, 1
H), 5.91 (dd, J = 11.8, 8.1 Hz, 1 H), 6.33 (d, J = 2.3 Hz, 1 H), 6.37
(dd, J = 8.2, 2.3 Hz, 1 H), 6.50 (br dd, J = 8.1, 1.4 Hz, 1 H), 6.77
(d, J = 8.2 Hz, 1 H), 7.23 (m, 2 H), 7.30–7.45 (m, 9 H), 7.68 (d,
J = 6.7 Hz, 4 H).
13C NMR (150 MHz): d = 19.5, 19.9, 26.6, 30.1, 42.6, 48.2, 65.9,
70.9, 104.8, 112.5, 117.8, 124.1, 127.81, 127.9, 128.5, 128.8, 130.0,
133.0, 133.3, 133.8, 135.6, 135.7, 138.6, 143.4, 155.5, 157.2, 200.5.
HRFABMS: m/z [M + Na]+ calcd for C39H242O4Si + Na: 625.2750;
found: 625.2728.
IR (ATR): 1670 cm–1.
1H NMR (400 MHz): d = 1.13 (s, 9 H), 1.75 (ddd, J = 2.5, 1.3, 1.3
Hz, 1 H), 2.16 (dddq, J = 18.3, 10.4, 2.5, 2.5 Hz, 1 H), 2.31 (dd,
J = 16.1, 13.2 Hz, 1 H), 2.32–2.39 (m, 1 H), 2.34 (dif. ddd,
J = 16.1, 3.7, 1.5 Hz, 1 H), 2.58–2.63 (m, 1 H), 3.19, 3.23 (d each,
J = 15.9 Hz, 1 H), 4.28, 4.31 (d each, J = 12.4 Hz, 1 H), 4.65, 4.82
(s each, 1 H), 6.06 (s, 1 H), 6.61 (ddq, J = 5.7, 2.8, 1.3 Hz, 1 H), 6.99
(dif. dd, J = 6.3, 2.8 Hz, 2 H), 7.04 (s, 1 H), 7.21 (dd, J = 5.1, 1.8
Hz, 2 H), 7.38 (dif. t, J = 7.3 Hz, 5 H), 7.45 (dif. t, J = 7.4 Hz, 2 H),
7.70 (dif. dd, J = 8.1, 1.4 Hz, 4 H).
13C NMR (100 MHz): d = 15.7, 19.7, 26.5, 31.7, 33.9, 40.6, 43.3,
69.8, 105.2, 110.9, 115.9, 121.6, 127.0, 127.8, 128.3, 130.2, 130.8,
132.6, 134.8, 135.2, 135.6, 136.4, 144.7, 149.7, 150.3, 154.8, 199.8.
(R)-3-[2-Benzyloxy-4-(tert-butyldiphenylsilyloxy)phenyl]-2-
cyclohexylpropionaldehyde (35)
HREIMS: m/z [M]+ calcd for C39H4135ClO3Si: 620.2513; found:
BF3·OEt2 (0.66 mL, 5.21 mmol) was added to a solution of crude 29
(2.6 g), which was prepared from 26 (2.04 g, 3.48 mmol) and
MCPBA (65%, 1.21 g, 4.55 mmol), in Et2O (20 mL) at –20 °C and
the mixture was stirred at –20 °C for 40 min. H2O (50 mL) was add-
ed and the mixture was extracted with Et2O (2 × 100 mL). The com-
bined organic layers were washed with brine (1 × 50 mL), and dried
(MgSO4). The solvent was evaporated in vacuo and the residue was
purified by CC (n-hexane–acetone, 7:1) to give 35 as a colorless oil
(1.02 g, 49% from 26, a 1:1 mixture of diastereoisomers).
620.2496.
(R)-5-[3-(2-Benzyloxy-4-tert-butyldiphenylsilyloxyphenyl)-1,2-
epoxypropan-2-yl]-2-methylcyclohex-2-en-1-one (29)
To a solution of 26 (308 mg, 0.52 mmol) in CH2Cl2 (3 mL), was
added MCPBA (65%, 182 mg, 0.69 mmol) at –10 °C and the mix-
ture was stirred at –10 °C for 18 h. Aq 10% Na2S2O3 was added and
the mixture was extracted with CHCl3 (2 × 30 mL). The combined
organic layers were washed with sat. aq NaHCO3 (2 × 20 mL) and
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

PAPER
Boron Trichloride Mediated Claisen Rearrangement of Resorcinol Derivatives
1795
IR (ATR): 1772, 1672 cm–1.
1H NMR (400 MHz): d = 1.10 (s, 9 H), 1.73 (br s, 1 H), 1.77 (br s,
3 H), 2.39 (dddq, J = 18.2, 10.5, 2.7, 2.7 Hz, 1 H), 2.48 (dd,
J = 16.0, 13.3 Hz, 1 H), 2.48–2.55 (m, 1 H), 2.64 (ddd, J = 16.0,
3.7, 1.2 Hz, 1 H), 2.98–3.06 (m, 1 H), 4.10 (br s, 2 H), 4.66 (s, 2 H),
6.35 (d, J = 2.2 Hz, 1 H), 6.37 (s, 1 H), 6.39 (dd, J = 8.3, 2.2 Hz, 1
H), 6.74 (ddq, J = 5.6, 2.7, 1.2 Hz, 1 H), 6.90 (d, J = 8.3 Hz, 1 H),
7.21 (dif. d, J = 7.7 Hz, 2 H), 7.30 (dif. t, J = 8.0 Hz, 3 H), 7.37 (dif.
t, J = 7.9 Hz, 4 H), 7.43 (dif. t, J = 7.4 Hz, 2 H), 7.70 (dif. d, J = 8.1
Hz, 4 H).
1H NMR (400 MHz): d = 1.088, 1.090 (s each, 9 H), 1.731, 1.734
(br s each, 3H), 2.09–2.26 (m, 6 H), 2.32–2.51 (m, 4 H), 2.53–2.60
(m, 2 H), 2.72–2.84 (m, 4 H), 4.64, 4.65 (s each, 2 H), 6.30 (dif. d,
J = 2.4 Hz, 2 H), 6.31 (dif. dd, J = 6.8, 2.4 Hz, 2 H), 6.55–6.57,
6.60–6.63 (m each, 1 H), 6.81 (d, J = 8.6 Hz, 2 H), 7.21–7.25 (m, 4
H), 7.30–7.45 (m, 18 H), 7.68 (dif. dd, J = 8.1, 1.5 Hz, 8 H), 9.53,
9.54 (s each, 1 H).
13C NMR (100 MHz): d = 15.60, 15.62, 19.4, 26.5, 26.8, 26.9, 29.3,
29.7, 35.0, 35.3, 41.4, 41.7, 55.5, 55.7, 69.8, 104.35, 104.43, 111.8,
119.19, 119.20, 127.5, 127.6, 127.7, 128.0, 128.47, 128.48, 129.9,
130.8, 132.9, 135.4, 135.45, 135.50, 136.5, 144.3, 144.4, 155.5,
156.74, 156.75, 198.8, 198.9, 203.9, 204.0.
13C NMR (150 MHz): d = 15.6, 19.4, 26.5, 32.2, 40.3, 43.7, 60.3,
70.3, 105.1, 112.1, 119.0, 123.8, 127.1, 127.8, 127.9, 128.5, 129.9,
130.5, 132.8, 135.2, 135.5, 136.5, 141.7, 144.9, 156.0, 156.4, 199.9.
HRFABMS: m/z [M + H]+ calcd for C39H42O4Si: 602.2852; found:
602.2823.
HREIMS: m/z [M]+ calcd for C39H42O4Si: 602.2852; found:
602.2765.
E-Isomer
[a]D24 +96.7 (c 1.2, CHCl3).
3-[2-Benzyloxy-4-(tert-butyldiphenylsilyloxy)phenyl]-2-cyclo-
hexylpropenal (36)
IR (ATR): 3447, 1668 cm–1.
A solution of 35 (6.24 g, 10.3 mmol) and DDQ (3.05 g, 13.4 mmol)
in benzene (60 mL) was stirred under reflux for 7 h. After cooling,
a mixture of EtOAc and n-hexane (10:1) was added and the mixture
was washed with aq 10% NaOH (3 × 200 mL) and brine (1 × 200
mL), and dried (MgSO4). The solvent was evaporated in vacuo and
the residue was purified by CC (n-hexane–EtOAc, 7:1) to give 36
as a yellow oil (3.29 g, 53%, E/Z = 1:3) and recovered 35 (475 mg,
8%).
1H NMR (400 MHz): d = 1.08 (s, 9 H), 1.46 (t, J = 6.0 Hz, 1 H),
1.75 (ddd, J = 2.5, 1.3, 1.3 Hz, 3 H), 2.20 (dif. ddd, J = 18.3, 5.8,
4.8 Hz, 1 H), 2.40 (ddd, J = 16.1, 3.8, 1.3 Hz, 1 H), 2.53–2.63 (m,
1 H), 2.61 (dd, J = 16.1, 14.4 Hz, 1 H), 3.32 (dddd, J = 14.4, 11.1,
4.0, 4.0 Hz, 1 H), 4.25 (d, J = 6.0 Hz, 2 H), 4.66, 4.69 (d each,
J = 12.5 Hz, 1 H), 6.30 (d, J = 2.3 Hz, 1 H), 6.35 (dd, J = 8.3, 2.3
Hz, 1 H), 6.52 (s, 1 H), 6.67 (dif. d, J = 5.8 Hz, 1 H), 6.80 (d, J = 8.3
Hz, 1 H), 7.18 (dif. dd, J = 7.4, 1.9 Hz, 2 H), 7.26–7.32 (m, 3 H),
7.35 (dif. t, J = 7.9 Hz, C6H5, 4 H), 7.42 (dif. t, J = 7.9 Hz, 2 H),
7.67 (dif. d, J = 8.0 Hz, 4 H).
13C NMR (100 MHz): d = 15.7, 19.4, 26.5, 31.3, 36.4, 43.1, 64.8,
69.9, 105.0, 111.9, 118.8, 125.0, 127.0, 127.7, 127.7, 128.4, 129.7,
129.9, 132.8, 135.0, 135.5, 136.7, 141.0, 145.3, 156.0, 156.6, 199.6.
HRFABMS: m/z [M + H]+ calcd for C39H42O4Si: 602.2852; found:
602.2808.
IR (ATR): 1670 cm–1.
1H NMR (400 MHz): d = 1.10 (s, 3.6 H), 1.11 (s, 9 H), 1.76–1.78
(m, 4.2 H), 2.14 (br ddd, J = 19.0, 5.1, 5.1 Hz, 0.4 H), 2.29–2.39 (m,
1.4 H), 2.47–2.57 (m, 3 H), 3.11 (dddq, J = 19.0, 11.7, 2.6, 2.6 Hz,
0.4 H), 3.25 (dd, J = 15.8, 14.3 Hz, 0.4 H), 3.29–3.35 (m, 1 H), 3.45
(br dd, J = 3.1, 3.1 Hz, 0.4 H), 4.71 (s, 2 H), 4.72 (s, 0.8 H), 6.35 (d,
J = 2.2 Hz, 1.4 H), 6.40 (dd, J = 8.2, 2.2 Hz, 1 H), 6.42 (dd, J = 8.4,
2.2 Hz, 0.4 H), 6.70–6.73 (m, 1.4 H), 6.90 (d, J = 8.2 Hz, 1 H), 6.97
(d, J = 8.4 Hz, 0.4 H), 7.18 (dif. d, J = 7.9 Hz, 2.8 H), 7.30 (dif. t,
J = 7.5 Hz, 4.2 H), 7.38 (dif. t, J = 7.1 Hz, 5.6 H), 7.45–7.47 (m, 3.2
H), 7.57 (s, 1 H), 7.67–7.71 (m, 5.6 H), 9.46 (d, J = 2.0 Hz, 0.4 H),
9.72 (s, 1 H).
13C NMR (100 MHz): d = 15.7, 15.8, 19.4, 26.4, 29.4, 31.8, 34.4,
35.9, 41.3, 42.7, 60.3, 70.2, 104.9, 112.0, 112.4, 116.0, 116.69,
127.02, 127.1, 127.9, 128.0, 128.5, 129.9, 130.1, 132.3, 132.4,
133.1, 134.9, 135.35, 135.42, 136.07, 136.11, 140.6, 140.7, 142.0,
144.5, 145.3, 148.6, 157.5, 157.7, 158.6, 158.7, 192.7, 195.8, 199.2,
199.6.
(R,Z)-5-{3-[2-Benzyloxy-4-(tert-butyldiphenylsilyloxy)phenyl]-
1-(2-methoxyethoxy)methoxy-2-propen-2-yl}-2-methylcyclo-
hex-2-en-1-one (38)
To a solution of (Z)-37 (3.02 g, 5.02 mmol) in DMF (10 mL), were
added i-Pr2EtN (2.6 mL, 14.9 mmol) and MEMCl (1.4 mL, 12.3
mmol) and the mixture was stirred at 90 °C for 2 h. After cooling to
r.t., aq 5% HCl (50 mL) was added and the mixture was extracted
with EtOAc (2 × 300 mL). The organic layer was washed with aq
5% HCl (4 × 100 mL) and brine (1 × 200 mL), and dried (MgSO4).
The solvent was evaporated in vacuo and the residue was purified
by CC (n-hexane–EtOAc, 4:1) to give (Z)-38 as a colorless oil (2.82
g, 81%). Compound (E)-38 was prepared by the same procedure
from (E)-37 in 91% yield.
HREIMS: m/z [M]+ calcd for C39H40O4Si: 600.2696; found:
600.2734.
(R)-5-{3-[2-Benzyloxy-4-(tert-butyldiphenylsilyloxy)phenyl]-1-
hydroxyprop-2-en-2-yl}-2-methylcyclohex-2-en-1-one (37)
AcOH (2.75 mL, 48.0 mmol) was added to a suspension of NaBH4
(550 mg, 14.5 mmol) in benzene (10 mL) at r.t. and the mixture was
refluxed for 20 min. Compound 36 (2.19 g, 3.64 mmol, E/Z = 1:3)
in benzene (15 mL) was added at r.t. and the mixture was refluxed
for 2.5 h. After cooling to 0 °C, sat. aq NaHCO3 (30 mL) was added
and the mixture was extracted with CH2Cl2 (3 × 100 mL). The com-
bined organic layers were washed with sat. aq NaHCO3 (1 × 50 mL)
and brine (1 × 50 mL), and dried (MgSO4). The solvent was evapo-
rated in vacuo and the residue was purified by CC (n-hexane–
EtOAc, 3:1) to give (Z)-37 (1.31 g, 60%) and (E)-37 (291 mg, 13%)
as colorless oils.
(Z)-38
[a]D24 –21.1 (c 1.2, CHCl3).
IR (ATR): 1672 cm–1.
1H NMR (400 MHz): d = 1.09 (s, 9 H), 1.78 (br s, 3 H), 2.34–2.43
(m, 1 H), 2.47 (dd, J = 16.0, 13.5 Hz, 1 H), 2.46–2.56 (m, 1 H), 2.67
(ddd, J = 16.0, 3.7, 0.9 Hz, 1 H), 2.97–3.05 (m, 1 H), 3.33 (s, 3 H),
3.46 (dif. t, J = 4.6 Hz, 2 H), 3.64 (dif. t, J = 4.6 Hz, 2 H), 4.12 (s,
2 H), 4.67 (s, 4 H), 6.31 (d, J = 2.2 Hz, 1 H), 6.36 (dd, J = 8.2, 2.2
Hz, 1 H), 6.55 (s, 1 H), 6.75 (m, 1 H), 6.99 (d, J = 8.2 Hz, 1 H), 7.21
(dif. d, J = 7.7 Hz, 2 H), 7.26–7.45 (m, 9 H), 7.69 (dif. d, J = 7.5
Hz, 4 H).
13C NMR (100 MHz): d = 15.7, 19.5, 26.5, 32.1, 40.6, 43.7, 59.0,
65.7, 67.1, 69.9, 71.7, 95.4, 104.7, 111.7, 118.9, 125.2, 126.9,
127.7, 127.8, 128.4, 130.0, 130.4, 132.9, 135.3, 135.5, 136.9, 138.1,
144.9, 156.2, 156.8, 199.9.
Z-Isomer
[a]D24 -25.5 (c 1.0, CHCl3).
IR (ATR): 3419, 1666 cm–1.
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York

1796
F. Ito et al.
PAPER
HREIMS: m/z [M]+ calcd for C42H50O6Si: 690.3376; found:
690.3318.
(3) Gozzo, F. C.; Fernandes, S. A.; Rodorigues, D. C.; Eberlin,
M. N.; Marsaioli, A. J. J. Org. Chem. 2003, 68, 5493.
(4) Syamaia, M. S.; Ramamurthy, V. Tetrahedron 1988, 44,
7223.
(5) Gates, B. D.; Dalidowicz, P.; Tebben, A.; Wang, S.;
Swenton, J. S. J. Org. Chem. 1992, 57, 2135.
(E)-38
[a]D26 +81.8 (c 1.0, CHCl3).
IR (ATR): 1672 cm–1.
(6) Cairns, N.; Harwood, L. M.; Astles, D. P.; Orr, A. J. Chem.
Soc., Perkin Trans. 1 1994, 3095.
1H NMR (400 MHz): d = 1.08 (s, 9 H), 1.75 (br s, 3 H), 2.17 (dif.
ddd, J = 18.1, 4.9, 4.9 Hz, 1 H), 2.39 (ddd, J = 16.1, 3.7, 1.1 Hz, 1
H), 2.51–2.60 (m, 1 H), 2.61 (dd, J = 16.1, 14.3 Hz, 1 H), 3.26–3.35
(m, 1 H), 3.37 (s, 3 H), 3.52 (dif. t, J = 4.6 Hz, 2 H), 3.68 (dif. t,
J = 4.6 Hz, 2 H), 4.20 (s, 2 H), 4.67 (s, 2 H), 4.72 (s, 2 H), 6.29 (d,
J = 2.2 Hz, 1 H), 6.35 (dd, J = 8.3, 2.2 Hz, 1 H), 6.55 (s, 1 H), 6.66
(dif. d, J = 5.9 Hz, 1 H), 6.81 (d, J = 8.3 Hz, 1 H), 7.19 (dif. d,
J = 7.5 Hz, 2 H), 7.27–7.30 (m, 3 H), 7.35 (dif. t, J = 7.6 Hz, 4 H),
7.42 (dif. t, J = 7.3 Hz, 2 H), 7.67 (dif. d, J = 8.0 Hz, 4 H).
13C NMR (100 MHz): d = 15.7, 19.4, 26.5, 31.1, 36.5, 43.0, 59.0,
67.0, 69.2, 69.8, 71.7, 94.2, 104.9, 111.8, 118.8, 127.0, 127.6,
127.7, 128.3, 129.7, 129.9, 129.9, 132.8, 135.0, 135.5, 136.8, 137.2,
145.2, 156.0, 156.6, 199.7.
(7) (a) Chansakaow, S.; Ishikawa, T.; Seki, H.; Sekine, K.;
Okada, M.; Chaichantipyuth, C. J. Nat. Prod. 2000, 63, 173.
(b) Chansakaow, S.; Ishikawa, T.; Sekine, K.; Okada, M.;
Higuchi, Y.; Kudo, M.; Chaichantipyuth, C. Planta Med.
2000, 66, 572. (c) Iwasaki, M.; Watanabe, T.; Ishikawa, T.;
Chansakaouw, S.; Higuchi, Y.; Tahara, S. Heterocycles
2004, 63, 1375. (d) Ito, F.; Iwasaki, M.; Watanabe, T.;
Ishikawa, T.; Higuchi, Y. Org. Biomol. Chem. 2005, 3, 674.
(8) Total synthesis of (+)-miroestrol: Corey, E. J.; Wu, L. I. J.
Am. Chem. Soc. 1993, 115, 9327.
(9) For preliminary reports: Ito, F.; Kumamoto, T.; Ishikawa, T.
Tetrahedron Lett. 2005, 46, 7765.
(10) Davis, C. J.; Hurst, T. E.; Jacob, A. M.; Moody, C. J. J. Org.
Chem. 2005, 70, 4414; and references cited therein.
(11) Houry, S.; Geresh, S.; Shani, A. Isr. J. Chem. 1973, 11, 805.
(12) Hansen, H.-J. Abnormal Claisen Rearrangement and
Related Sigmatropic Rearrangements, In Mechanism of
Molecular Migrations, Vol. 3; Thyagarajan, B. S., Ed.;
Wiley-Interscience: New York, 1971, 177.
HREIMS: m/z [M]+ calcd for C43H50O6Si: 690.3376; found:
690.3392.
Isomerization of (E)-38 to (Z)-38
A solution of (E)-38 (526 mg, 0.76 mmol) and acetophenone (0.01
mL, 85.7 mmol, 0.11 mequiv) in benzene (15 mL) was irradiated by
UV light (400 W high pressure Hg lump, Pyrex filter) for 1 h. The
solvent was evaporated in vacuo and the residue was purified by CC
(n-hexane–EtOAc, 3:1) to give (E)-38 (150 mg, 29%) and (Z)-38
(215 mg, 41%).
(13) Scheinmann, F.; Barner, R.; Schmid, H. Helv. Chim. Acta
1968, 51, 1603.
(14) Fukuyama et al. reported the utilization of 1,1,1,3,3,3,-
hexamethyldisilazane and N,O-bis(trimethylsilyl)acetamide
as reagents for preventing abnormal Claisen rearrangement:
Fukuyama, T.; Li, T.; Peng, G. Tetrahedron Lett. 1994, 35,
2145.
Acknowledgment
F.I. acknowledges the Sasakawa Scientific Research Grant from
The Japan Science Society for the financial support.
(15) Weinges, K.; Schwarz, G. Liebigs Ann. Chem. 1993, 811.
(16) Murata, M.; Suzuki, M.; Noyori, R. Bull. Chem. Soc. Jpn.
1982, 55, 247.
(17) LDA-mediated ring expansion of carvone epoxide was
reported: Baldwin, J. E.; Broline, B. M. J. Am. Chem. Soc.
1982, 104, 2857.
(18) Itoh, A.; Hirose, Y.; Kahiwagi, H.; Masaki, Y. Heterocycles
1994, 38, 2165.
References
(1) Reviews: (a) Martin Castro, A. M. Chem. Rev. 2004, 104,
2939. (b) Jones, S. J.; Raulins, N. R. Org. React. 1975, 22, 1.
(2) (a) White, W. H.; Slater, C. D. J. Org. Chem. 1961, 26,
3631. (b) Bruce, J. M.; Roshan-Ali, Y. J. Chem. Soc., Perkin
Trans. 1 1981, 2677.
(19) Barker, P. L.; Bahia, C. Tetrahedron 1990, 46, 2691.
Synthesis 2007, No. 12, 1785–1796 © Thieme Stuttgart · New York