Formal meta-specific intramolecular Friedel-Crafts allylic alkylation of phenols through a spirocyclization-dienone-phenol rearrangement cascade

Article abstract of DOI:10.1016/j.tet.2013.09.042

Formal meta-specific intramolecular Friedel-Crafts allylic alkylation of phenols was achieved based on spirocyclization-dienone-phenol rearrangement cascades. Systematic screening of acid catalysts revealed that Sc(OTf) ₃ was a highly effective catalyst for dienone-phenol rearrangement of spiro[4.5]cyclohexadienones. Using 5 mol % of Sc(OTf)₃ as the promoter, various spirocyclic substrates were transformed into the corresponding phenol derivatives in good to excellent yield. Furthermore, the one-pot sequential spirocyclization-dienone-phenol rearrangement proceeded using a palladium and scandium multi-catalytic system or a triphenylmethyl cation single-catalyst system, providing the corresponding meta-allylated phenol derivatives in excellent yield.

Full text of DOI:10.1016/j.tet.2013.09.042

Tetrahedron 69 (2013) 9609e9615
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Formal meta-specific intramolecular FriedeleCrafts allylic alkylation
of phenols through a spirocyclizationedienoneephenol
rearrangement cascade
*
Mariko Yoshida, Tomoyuki Nozaki, Tetsuhiro Nemoto, Yasumasa Hamada
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 August 2013
Received in revised form 10 September 2013
Accepted 12 September 2013
Available online 19 September 2013
Formal meta-specific intramolecular FriedeleCrafts allylic alkylation of phenols was achieved based on
spirocyclizationedienoneephenol rearrangement cascades. Systematic screening of acid catalysts re-
vealed that Sc(OTf)3 was a highly effective catalyst for dienoneephenol rearrangement of spiro[4.5]cy-
clohexadienones. Using 5 mol % of Sc(OTf)3 as the promoter, various spirocyclic substrates were
transformed into the corresponding phenol derivatives in good to excellent yield. Furthermore, the one-
pot sequential spirocyclizationedienoneephenol rearrangement proceeded using a palladium and
scandium multi-catalytic system or a triphenylmethyl cation single-catalyst system, providing the cor-
responding meta-allylated phenol derivatives in excellent yield.
Keywords:
Alkylation
Cascade reaction
FriedeleCrafts reaction
Rearrangement
Spiro compounds
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
a Pd-catalyzed intramolecular ipso-FriedeleCrafts allylic alkyl-
ation of para-substituted phenol derivatives, which produced
Aromatic ring functionalization through a CeC bond forming
reaction is an important process in organic synthesis because
such molecular frameworks are widely distributed in natural
products, pharmaceuticals, and functional materials. Various
synthetic methods have therefore been developed based on the
lithiationealkylation sequence,1 transition metal-catalyzed cross-
spiro[4.5]cyclohexadienones in excellent yield [Scheme 1(a)].7
Moreover, the spirocyclization could be extended to
a Pd-
catalyzed sequential process: Heck insertion to an alleneeipso-
FriedeleCrafts allylic alkylation cascade [Scheme 1(b)].7d 3,3-
Disubstituted cyclohexadienones undergo dienoneephenol rear-
rangement in the presence of an acid catalyst to give the corre-
sponding 3,4-disubstituted phenol derivatives.8 We hypothesized
that the Pd-catalyzed spirocyclization and an acid-catalyzed
dienoneephenol rearrangement sequence would lead to a for-
mal meta-specific intramolecular FriedeleCrafts allylic alkylation
of phenols. Furthermore, if these two reactions could be per-
formed in a single pot without interfering with the individual
catalytic processes, the synthetic efficiency could be significantly
increased in terms of pot economy.9 Herein we report two sets of
formal meta-specific intramolecular FriedeleCrafts allylic alkyl-
ations of phenols through a spirocyclizationedienoneephenol
rearrangement cascade.
coupling reactions,2
h
6-arene metal complex-mediated re-
actions,3 transition metal-mediated CeH bond functionalization,4
and others. FriedeleCrafts reaction is another useful method for
synthesizing functionalized aromatic rings through a nucleo-
philic aromatic substitution.5 Both electronic and steric proper-
ties of substituents on the aromatic ring generally affect the
reactivity, as well as the reaction orientation. When phenols are
utilized as aromatic substrates in FriedeleCrafts reaction, nucle-
ophilic aromatic substitution exclusively occurs at the ortho- and/
or para-positions to the hydroxyl group, providing multi-
substituted aromatic compounds. On the other hand, direct in-
troduction of substituents at the meta-position to the hydroxyl
group remains a highly challenging task in modern synthetic
organic chemistry.6
2. Results and discussions
As part of our ongoing studies aimed at developing novel
synthetic method for spirocyclic molecules, we recently reported
Our investigation began with spiro[4.5]cyclohexadienone 1a,
which was prepared using the Pd-catalyzed intramolecular ipso-
FriedeleCrafts allylic alkylation of phenols (Table 1). We first
examined the reaction using
most conventional Brønsted acid promoter for dienoneephenol
5 mol % of TsOH$H2O, the
* Corresponding author. Tel./fax: þ81 43 226 2920; e-mail addresses: hamada@
p.chiba-u.ac.jp, y-hamada@faculty.chiba-u.jp (Y. Hamada).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.09.042

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M. Yoshida et al. / Tetrahedron 69 (2013) 9609e9615
rearrangements. Tetralinol derivative 2a was obtained in 91%
yield as a single regioisomer, indicating selective migration of
a branched alkyl group during this transformation (entry 1).
Lewis acidic reagents, such as BF3$OEt2 or BCl3 are also utilized as
promoters in dienoneephenol rearrangements. The reaction
proceeded smoothly in the presence of 5 mol % of BF3$OEt2,
giving 2a in a similar yield with that obtained using TsOH$H2O
(entry 2). Screening of other Lewis acids was performed using
5 mol % of acid catalyst in CH3CN at room temperature (Entries
3e9). A variety of metal triflates and metal halides functioned as
effective catalysts for this transformation. Among the examined
Lewis acids, Sc(OTf)3 was selected as the best catalyst in terms of
high yield, water/protic solvent compatibility,10 and easy han-
dling. In addition, the solvent effect was examined using 5 mol %
of Sc(OTf)3 (Entries 10e13). Bicyclic product 2a was obtained in
91% yield when CH3NO2 was used as a solvent.
Scheme 1. Pd-catalyzed intramolecular ipso-FriedeleCrafts allylic alkylation of
phenols.
With the optimized reaction conditions in hand, the substrate
scope of dienoneephenol rearrangement was explored using
TsOH$H2O as a Brønsted acid catalyst or Sc(OTf)3 as a Lewis acid
catalyst (Table 2). In addition to the model substrate 1a (entry 1),
spirocyclohexadienones 1b and 1c, bearing dimethyl or dime-
Table 1
Screening of the acid catalyst
thoxy groups at the
a-positions to the ketone, were converted
into the corresponding tetralinols 2b and 2c in excellent yield
under both catalytic reaction conditions (Entries 2 and 3). The use
of substrates with a substituent at the b-position to ketones 1d
and 1e significantly decreased the reactivity. The Sc(OTf)3 catalyst
system was more suitable for this type of substrate and products
2d and 2e were obtained in 80% yield and 53% yield, respectively
(Entries 4 and 5). More striking differences in the reactivity be-
tween the two catalyst conditions were observed when naph-
thoquinone derivative 2f was used as a starting material (entry 6).
Sc(OTf)3 was also effective when the substrates were spi-
rocyclohexadienones bearing a trans-substituted olefin 1g and 1h
or a gem-substituted olefin 1i. Using 5 mol % of the catalyst, the
corresponding products 2gei were obtained in 77%e93% yield
(entry 7e9). On the other hand, the TsOH$H2O catalyst system
afforded much better results when di-tert-butylmalonate teth-
ered substrate 1j was used (entry 10).11
Entry
Acid catalyst
Solvent
Yield (%)a
1
2
3
4
5
6
7
8
TsOH$H2O
BF3$OEt2
Mg(OTf)2
Zn(OTf)2
Cu(OTf)2
Sc(OTf)3
Yb(OTf)3
FeCl3
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3NO2
Toluene
CH2Cl2
THF
91
92
No reaction
9
84
91
90
90
89
91
64
75
38
9
AuCl3
10
11
12
13
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
a
Isolated yield.
Table 2
Scope and Limitation
Entry
Substrate
Solvent
Time (h)
Temp (ꢀC)
X (mol %)
Product
Yield (%)a
Catalyst: TsOH$H2O
Catalyst: Sc(OTf)3
1
2
3
1a
1b
1c
1d
1e
1f
1g
1h
1i
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
3
3
3
14
57
30
3
3
2
0.5
rt
rt
rt
rt
Reflux
rt
rt
rt
rt
5
5
5
5
20
5
5
5
5
5
2a
2b
2c
2d
2e
2f
2g
2h
2i
91
98
91
26
31
4
65
74
39
96
91
98
93
80
53
80
93
93
77
17d
4b,c
5b,c
6b,c
7c
8c
9
10
1j
rt
2j
a
Isolated yield.
b
c
Diastereomeric mixtures were used as substrates. 1d (dr. 14:1), 1e (dr. 1.3:1), 1f (dr. 2.1:1).
Reactions were carried out under diluted conditions (0.02 M) to prevent the formation of side products.
Reaction time: 15 h.
d

M. Yoshida et al. / Tetrahedron 69 (2013) 9609e9615
9611
Spirocyclic compounds 1 are available in an optically active
form by changing the achiral triphenylphosphine into a chiral
phosphorus ligand in the Pd-catalyzed intramolecular ipso-Frie-
deleCrafts allylic alkylation of phenols. When optically active 1a
(66% ee)12 was treated with the optimized reaction conditions, 2a
was obtained in 98% yield without a significant loss of enantio-
meric purity (65% ee). This result clearly demonstrated the ap-
plicability of the present cascade process to the asymmetric
synthesis (Scheme 2).13
then treated with 5 mol % of acid catalyst in CH3CN to give 2b in 98%
yield (See Table 2, entry 2). Consequently, the formal meta-specific
FriedeleCrafts allylic alkylation of 3b proceeded in 89% overall yield
in a two-pot reaction [Scheme 3(a)]. On the other hand, after
completion of the Pd-catalyzed spirocyclization of 3b in CH3CN,
20 mol % of Sc(OTf)3 were directly added to the reaction mixture.
The second dienoneephenol rearrangement proceeded to com-
pletion in 0.5 h and the target compound 2b was obtained in 93%
yield in the one-pot process [Scheme 3(b)].15
Scheme 2. Dienoneephenol rearrangement using an optically active substrate.
The compatibility of the second catalysis with the first reaction
conditions is key to the success of the one-pot sequential spi-
rocyclizationedienoneephenol rearrangement using
a multi-
catalytic reaction system. Therefore, we performed experiments
to investigate the influence of the constituents of the first Pd-
catalyzed spirocyclization on the second acid catalysis (Table 3).14
First, a dienoneephenol rearrangement of 1a was examined using
5 mol % of TsOH$H2O in the presence of additives. Compared with
the control experiments (entry 1), the addition of MeOH (1 equiv)
to the reaction did not affect the reactivity (entry 4). In contrast, the
addition of 5 mol % of Pd(dba)2 or 12 mol % of PPh3 retarded the
catalytic activities (Entries 2 and 3). The same experiments were
also performed using Sc(OTf)3 as the catalyst. Reactions proceeded
smoothly in the presence of 5 mol % of Pd(dba)2 or 1 equiv of MeOH
(Entries 6 and 8). On the other hand, there was a decreased re-
activity when using PPh3 as the additive probably due to the Lewis
basic properties of PPh3 (entry 7). A prolonged reaction time,
however, resulted in gradual consumption of 1a (entry 7), sug-
gesting that the target one-pot sequential catalysis would proceed
by using a slightly larger amount of Sc(OTf)3 than that of PPh3.
Scheme 3. One-pot multi-catalytic sequential process.
When both Pd catalyst and Sc(OTf)3 coexisted in the reaction
mixture at the initial stage of the reaction, the first Pd-catalyzed
spirocyclization did not proceed at all. We thus turned our atten-
tion to develop a spirocyclizationedienoneephenol rearrangement
cascade process promoted by a single-catalyst. Our reaction design
towards this end is outlined in Scheme 4. Treatment of allylic al-
cohol derivatives I with an acid catalyst should lead to the
formation of allylic cation intermediates II. Subsequent ipso-Frie-
deleCrafts allylic alkylation of phenols would provide spirocyclic
molecules III.16 Dienoneephenol rearrangement of III should pro-
ceed sequentially in the presence of the same acid catalyst, pro-
ducing formal meta-specific FriedeleCrafts reaction product IV.
Table 3
Compatibility of the reaction conditions
Entry
Acid catalyst
Additive
Yield (%)a
1
2
3
4
5
6
7
8
TsOH$H2O
TsOH$H2O
TsOH$H2O
TsOH$H2O
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
d
>99
9
14
Pd(dba)2 (5 mol %)
PPh3 (12 mol %)
MeOH (1 equiv)
d
94
>99
>99
50 (78)b
97
Pd(dba)2 (5 mol %)
PPh3 (12 mol %)
MeOH (1 equiv)
a
Yields were determined by 1H NMR analysis of the crude sample.
Reaction time: 12 h.
b
Scheme 4. Plan for the acid-catalyzed cascade reaction.
The promising data in the compatibility studies led us to ex-
The reaction conditions were optimized using compound 4h as
a substrate (Table 4). We first examined the reaction using 5 mol %
of Sc(OTf)3 in CH3CN at room temperature. The desired product 2h
was obtained in 60% yield, accompanied by the formation of lactone
derivative 5h as a diastereomeric mixture (31% yield, dr. 7.0:1)
amine a one-pot sequential multi-catalytic process using 3b as
a substrate. Pd-catalyzed intramolecular ipso-FriedeleCrafts allylic
alkylation of 3b proceeded under the optimized reaction condi-
tions, providing 1b in 91% isolated yield. The obtained product was

9612
M. Yoshida et al. / Tetrahedron 69 (2013) 9609e9615
(entry 1).17 The reaction media significantly affected the reactivity,
and the best results were obtained when the reaction was per-
formed in CH3NO2 (entry 4). Screening of other Lewis acids
revealed that triphenylmethyl perchlorate was the most effective
catalyst for this cascade reaction and 2h was obtained in 85% yield
without noticeable formation of 5h (entry 8). The reaction using
20 mol % of Brønsted acid catalysts gave less satisfactory results
(Entries 9 and 10). Furthermore, the reaction using simple allylic
alcohol substrate 4a proceeded under the optimized conditions,
providing 2a in 59% yield (entry 11). This result demonstrated the
potential for broad substrate applicability of this catalytic cascade
reaction.18
DAICEL CHIRALPAK AD-H, DAICEL CHIRALCEL OD-H; mobile
phase, hexanee2-propanol. Reactions were carried out in dry
solvent under argon atmosphere. Other reagents were purified by
the usual methods.
4.2. Pd-catalyzed spirocyclization of phenols
Spirocyclic derivatives 1aeh, and 1j were prepared from the
corresponding para-substituted phenol derivatives with an allyl
carbonate unit according to the typical experimental procedure.
Spirocyclic compound 1i was prepared using the reported method.
See our preceding papers for details.7
Table 4
Optimization of the reaction conditions
Entry
Substrate
Acid catalyst
Solvent
Time (h)
Yield of 2 (%)
Yield of 5 (%) [diastereomeric ratio]
1
2
3
4
5
6
7
8
4h
4h
4h
4h
4h
4h
4h
4h
4h
4h
4a
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Yb(OTf)3
Cu(OTf)2
Zn(OTf)2
Ph3CClO4
TsOH$H2Oa
TFAa
CH3CN
CH2Cl2
THF
3
3
3
3
3
3
3
3
60
22
4
69
45
54
39
85
31
7
31 [7.0:1]
10 [2.6:1]
32 [3.0:1]
12 [1:1.2]
13 [12.3:1]
10 [2.9:1]
7 [4.6:1]
d
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH2Cl2
CH2Cl2
CH3NO2
9
10
11
24
24
24
57 [1:1.1]
15 [2.0:1]
15 [1.2:1]
Ph3CClO4
59
a
20 mol % of acid catalyst was used.
3. Conclusion
4.2.1. Typical experimental procedure for the Pd-catalyzed intra-
molecular ipso-FriedeleCrafts allylic alkylation of phenols. Compound
We successfully achieved a formal meta-specific intramolecular
FriedeleCrafts allylic alkylation of phenols based on a one-pot se-
quential catalysis. Systematic screening of acid catalysts revealed
that Sc(OTf)3 was a highly effective catalyst for dienoneephenol
rearrangement of spiro[4.5]cyclohexadienones. The one-pot se-
quential spirocyclizationedienoneephenol rearrangement pro-
ceeded using a palladium and scandium multi-catalytic system or
a triphenylmethyl cation single-catalyst system, providing the 3,4-
disubstituted phenol derivatives in good to excellent yield.
3b (31.7 mg, 0.080 mmol), Pd(dba)2 (2.3 mg, 4.0
mmol), and PPh3
(2.5 mg, 9.6 mol) were dissolved in CH2Cl2 (0.40 mL), and the
m
resulting mixture was stirred at room temperature. After 4 h, the
reaction was quenched with satd aq NH4Cl, and the mixture was
extracted with AcOEt. The organic layer was washed with brine,
dried over Na2SO4, and then concentrated in vacuo. The obtained
residue was purified by flash column chromatography (SiO2,
hexaneeAcOEt¼4/1) to give 1b (23.4 mg, 91% yield) as white solid.
4.2.2. Dimethyl 8-oxo-4-vinylspiro[4.5]deca-6,9-diene-2,2-
4. Experimental
4.1. General
dicarboxylate (1a). Colorless oil; IR (ATR)
1625, 1435, 1408, 1253, 1200, 1173, 1146, 1093, 1069, 993, 929, 886,
858, 771 cmꢁ1 1H NMR (CDCl3):
n 2954, 1728, 1662,
;
d
2.45 (d, J¼14.4 Hz, 1H),
2.52e2.70 (m, 3H), 2.84 (ddd, J¼6.8, 6.8, 13.2 Hz, 1H), 3.79 (s, 3H),
3.80 (s, 3H), 5.00 (d, J¼18.4 Hz,1H), 5.01 (d, J¼9.6 Hz,1H), 5.41 (ddd,
J¼6.8, 9.6, 18.4 Hz, 1H), 6.26 (dd, J¼2.0, 10.0 Hz, 1H), 6.31 (dd, J¼2.0,
10.0 Hz, 1H), 6.73 (dd, J¼3.2, 10.0 Hz, 1H), 6.86 (dd, J¼3.2, 10.0 Hz,
Infrared (IR) spectra were recorded on a JASCO FT/IR 230
Fourier transform infrared spectrophotometer, equipped with
ATR (Smiths Detection, DuraSample IR II). NMR spectra were
recorded on a JEOL ecp 400 spectrometer, operating at 400 MHz
for 1H NMR, and 100 MHz for 13C NMR. Chemical shifts in CDCl3,
1H); 13C NMR (CDCl3):
d 38.4, 43.4, 52.0, 53.2, 53.2, 53.4, 58.4, 117.7,
129.1, 130.0, 133.7, 148.9, 152.9, 172.0, 172.3, 185.8; EI-LRMS m/z 290
(Mþ); EI-HRMS Calcd for C16H18O5 (Mþ): 290.1154. Found: 290.1149.
The enantiomeric excess was determined by chiral HPLC analysis
(DAICEL CHIRALCEL OD-H, hexane/2-propanol¼90/10, flow rate:
0.5 mL/min, tR 34.6 min (minor-isomer) and 46.8 min (major-iso-
mer), detection at 254 nm).
were reported downfield from TMS (¼0 ppm) for 1H NMR. For 13
C
NMR, chemical shifts were reported in the scale relative to the
solvent signal [CHCl3 (77.0 ppm)] as an internal reference. EI mass
spectra were measured on JEOL GCmate. ESI mass spectra were
measured on JEOL AccuTOF LC-plus JMS-T100L. The enantiomeric
excess (ee) was determined by HPLC analysis. HPLC was per-
formed on JASCO HPLC systems consisting of the following:
pump, PU-980; detector, UV-970, measured at 254 nm; column,
4.2.3. Dimethyl 7,9-dimethyl-8-oxo-4-vinylspiro[4.5]deca-6,9-diene-
2,2-dicarboxylate (1b). White solid; mp 73e75 ꢀC; IR (ATR)
n 2953,

M. Yoshida et al. / Tetrahedron 69 (2013) 9609e9615
9613
1731,1668,1635,1435,1254,1199,1086, 909 cmꢁ1; 1H NMR (CDCl3):
14.0 Hz, 1H), 2.63 (dd, J¼6.8, 14.0 Hz, 1H), 2.65 (d, J¼14.8 Hz, 1H),
2.79 (ddd, J¼6.8, 6.8, 14.0 Hz, 1H), 3.78 (s, 3H), 3.79 (s, 3H),
5.00e5.06 (m, 1H), 5.42 (dq, J¼12.8, 6.4 Hz, 1H), 6.25e6.30 (m, 2H),
6.70 (dd, J¼3.2, 9.6 Hz, 1H), 6.86 (dd, J¼3.2, 10.4 Hz, 1H); 13C NMR
d
1.88 (d, J¼1.6 Hz, 3H),1.90 (d, J¼1.6 Hz, 3H), 2.38 (d, J¼14.4 Hz,1H),
2.50e2.65 (m, 3H), 2.75e2.82 (m, 1H), 3.79 (s, 6H), 4.93e4.97 (m,
2H), 5.38 (ddd, J¼6.8, 10.0, 17.2 Hz, 1H), 6.49 (dd, J¼1.6, 2.8 Hz, 1H),
6.60 (dd, J¼1.6, 2.8 Hz, 1H); 13C NMR (CDCl3):
d
16.0, 16.3, 38.5, 43.7,
(CDCl3): d 17.7, 39.1, 43.4, 52.2, 52.9, 53.1, 53.2, 58.4, 126.3, 128.8,
51.3, 53.1, 53.2, 53.3, 58.4, 117.0, 134.4, 135.0, 136.0, 144.0, 148.4,
129.1, 129.9, 149.3, 153.4, 172.1, 172.4, 186.1; EI-LRMS m/z 304 (Mþ);
172.3,172.6, 187.2; ESI-LRMS m/z 341 (MþNaþ); ESI-HRMS Calcd for
EI-HRMS Calcd for C17H20O5 (Mþ): 304.1311. Found: 304.1304.
C
18H22NaO5 (MþNaþ): 341.1365. Found: 341.1322.
4.2.9. (E)-Dimethyl 6-methyl-8-oxo-4-styrylspiro[4.5]deca-6,9-
4.2.4. Dimethyl 7,9-dimethoxy-8-oxo-4-vinylspiro[4.5]deca-6,9-
diene-2,2-dicarboxylate (1h). Colorless solid; IR (ATR)
1729, 1662, 1625, 1435, 1252, 1199, 1172, 1092, 964, 858, 751,
693 cmꢁ1; 1H NMR (CDCl3):
n 2958,
diene-2,2-dicarboxylate (1c). White solid; mp 119e120 ꢀC; IR
(ATR)
n
2954, 1729, 1668, 1617, 1436, 1253, 1200, 1109, 928,
d
2.48 (d, J¼14.4 Hz, 1H), 2.63e2.78 (m,
871 cmꢁ1; 1H NMR (CDCl3):
d
2.40 (d, J¼14.4 Hz, 1H), 2.59e2.69 (m,
3H), 2.99e3.06 (m, 1H), 3.80 (s, 3H), 3.81 (s, 3H), 5.78 (dd, J¼7.6,
16.0 Hz, 1H), 6.27e6.37 (m, 3H), 6.79 (dd, J¼2.8, 10.0 Hz, 1H), 6.94
2H), 2.77 (d, J¼14.4 Hz, 1H), 2.81e2.88 (m, 1H), 3.64 (s, 3H), 3.69 (s,
3H), 3.79 (s, 3H), 3.80 (s, 3H), 4.95e5.00 (m, 2H), 5.39 (ddd, J¼7.2,
(dd, J¼2.8, 10.0 Hz, 1H), 7.18e7.28 (m, 5H); 13C NMR (CDCl3):
d 39.0,
10.0, 17.2 Hz, 1H), 5.68 (d, J¼2.0 Hz, 1H), 5.83 (d, J¼2.0 Hz, 1H); 13
C
43.6, 52.4, 52.9, 53.2, 53.3, 58.5, 125.1, 126.2 (2C), 127.7, 128.5 (2C),
129.3, 130.2, 132.7, 136.2, 149.0, 172.0, 172.3, 185.8; EI-LRMS m/z 366
(Mþ); EI-HRMS Calcd for C22H22O5 (Mþ): 366.1467. Found: 366.1471.
NMR (CDCl3):
d 38.4, 45.7, 50.1, 53.2, 53.2, 54.2, 55.2, 55.3, 58.1,
115.9, 117.4, 120.3, 134.2, 150.8, 151.7, 172.6, 172.6, 176.5; ESI-LRMS
m/z 373 (MþNaþ); ESI-HRMS Calcd for C18H22NaO7 (MþNaþ):
373.1263. Found: 373.1226.
4.2.10. Dimethyl 8-oxo-4-(1-phenylvinyl)spiro[4.5]deca-6,9-diene-
2,2-dicarboxylate (1i). Colorless oil; IR (ATR):
n
1729, 1662, 1252,
4.2.5. Dimethyl 6-methyl-8-oxo-4-vinylspiro[4.5]deca-6,9-diene-2,2-
dicarboxylate (1d). The titled compound was obtained as an in-
1200, 856, 733, 701 cmꢁ1 1H NMR (CDCl3):
;
d
2.35 (d, J¼14.8 Hz,
1H), 2.70 (d, J¼14.8 Hz, 1H), 2.76 (dd, J¼6.4, 14.0 Hz, 1H), 2.90 (dd,
J¼13.2, 14.0 Hz, 1H), 3.47 (dd, J¼6.0, 13.2 Hz, 1H), 3.79 (s, 3H), 3.83
(s, 3H), 5.10 (s, 1H), 5.11 (s, 1H), 5.59 (dd, J¼2.0, 10.0 Hz, 1H), 6.14
(dd, J¼2.0, 10.0 Hz, 1H), 6.44 (dd, J¼3.2, 10.0 Hz, 1H), 6.83 (dd, J¼3.2,
10.0 Hz, 1H), 7.02e7.05 (m, 2H), 7.17e7.20 (m, 3H); 13C NMR
separable mixture of diastereomers (white solid). IR (ATR)
1728, 1663, 1626, 1435, 1253, 1200, 1172, 1090, 930, 882, 849,
814 cmꢁ1; 1H NMR (CDCl3, major diastereomer):
2.05 (s, 3H), 2.33
n 2954,
d
(d, J¼15.2 Hz, 1H), 2.62 (d, J¼9.6 Hz, 12H), 2.88 (d, J¼15.2 Hz, 1H),
3.05 (dt, J¼7.2, 9.6 Hz, 1H), 3.79 (s, 3H), 3.81 (s, 3H), 4.97 (dd, J¼0.9,
18.0 Hz, 1H), 5.00 (dd, J¼0.9, 10.4 Hz, 1H), 5.38 (ddd, J¼7.2, 10.4,
18.0 Hz,1H), 6.24 (dd, J¼2.0,10.4 Hz,1H), 6.25 (d, J¼2.0 Hz,1H), 6.86
(CDCl3):
d 37.5, 44.1, 50.5, 52.9, 53.2, 53.3, 57.5, 114.0, 126.9 (2C),
127.7, 127.7, 128.0 (2C), 128.5, 141.7, 146.5, 149.3, 153.2, 171.9, 172.4,
185.6; ESI-LRMS m/z 389 (MþNaþ); ESI-HRMS Calcd for
(d, J¼10.4 Hz, 1H); 13C NMR (CDCl3, major diastereomer):
d
18.9,
C
22H22NaO5 (MþNaþ): 389.1359. Found: 389.1385.
38.4, 42.2, 51.2, 53.2, 53.3, 54.6, 58.3, 117.5, 128.2, 130.5, 133.9, 150.1,
159.2, 172.1, 172.6, 185.7; EI-LRMS m/z 304 (Mþ); EI-HRMS Calcd for
4.2.11. Di-tert-butyl 8-oxo-4-vinylspiro[4.5]deca-6,9-diene-2,2-
dicarboxylate (1j). White solid; mp 63e66 ꢀC; IR (ATR)
2978,
2933,1720,1666,1627,1457,1393,1368, 1281,1256,1211,1166,1139,
1094, 922, 857, 738 cmꢁ1 1H NMR (CDCl3):
1.47 (s, 9H), 1.48 (s,
C
17H20O5 (Mþ): 304.1311. Found: 304.1304.
n
4.2.6. Dimethyl 6-methoxy-8-oxo-4-vinylspiro[4.5]deca-6,9-diene-
;
d
2,2-dicarboxylate (1e). The titled compound was obtained as an
9H), 2.31 (d, J¼14.4 Hz, 1H), 2.46e2.56 (m, 2H), 2.60 (d, J¼14.4 Hz,
1H), 2.82 (ddd, J¼7.6, 7.6, 15.2 Hz,1H), 4.97e5.01 (m, 2H), 5.42 (ddd,
J¼7.6, 10.0, 17.6 Hz, 1H), 6.26 (dd, J¼2.0, 10.0 Hz, 1H), 6.30 (dd, J¼2.0,
10.0 Hz, 1H), 6.74 (dd, J¼3.2, 10.0 Hz, 1H), 6.88 (dd, J¼3.2, 10.0 Hz,
inseparable mixture of diastereomers (colorless oil). IR (ATR)
2954, 1732, 1658, 1592, 1436, 1375, 1337, 1256, 1219, 1104, 994,
855 cmꢁ1 1H NMR (CDCl3, major diastereomer):
2.37e2.44 (m,
n
;
d
1H), 2.49 (d, J¼14.0 Hz,1H), 2.67e2.96 (m, 2H), 3.26 (ddd, J¼7.2, 7.2,
14.0 Hz, 1H), 3.75 (s, 3H), 3.78 (s, 3H), 3.80 (s, 3H), 4.93e5.01 (m,
2H), 5.34e5.46 (m, 1H), 5.67 (d, J¼1.6 Hz, 1H), 6.14e6.20 (m, 1H),
6.65 (d, J¼10.0 Hz, 1H); 13C NMR (CDCl3, major diastereomer):
1H); 13C NMR (CDCl3):
d 27.8 (3C), 27.8 (3C), 38.2, 43.6, 52.2, 53.5,
60.0, 82.0, 82.0, 117.4, 129.1, 129.9, 134.3, 149.5, 153.5, 170.9, 171.2,
186.1; ESI-LRMS m/z 397 (MþNaþ); ESI-HRMS Calcd for
C
22H30NaO5 (MþNaþ): 397.1991. Found: 397.1979.
d
38.2, 42.6, 52.1, 53.1, 53.2, 53.5, 55.8, 58.3, 104.2, 117.5, 127.8, 134.1,
145.4, 172.1, 172.3, 174.6, 187.5; ESI-LRMS m/z 343 (MþNaþ); ESI-
4.3. Acid-catalyzed dienoneephenol rearrangement of spiro
[4.5]cyclohexadienones
HRMS Calcd for C17H20NaO6 (MþNaþ): 343.1158. Found: 343.1125.
4.2.7. Dimethyl
thalene)-4,4-dicarboxylate (1f). The titled compound was obtained
as an inseparable mixture of diastereomers (white solid). IR (ATR)
2954, 1729, 1663, 1599, 1435, 1269, 1202, 1172, 1090, 770 cmꢁ1; 1H
NMR (CDCl3, major diastereomer):
40-oxo-2-vinyl-40H-spiro(cyclopentane-1,10-naph-
4.3.1. Typical experimental procedure for Sc(OTf)3-catalyzed
dienoneephenol rearrangement of spiro[4.5]cyclohexadienone. 1b
(27.8 mg, 0.087 mmol), and Sc(OTf)3 (2.1 mg, 4.4 mmol) were dis-
solved in CH3CN (0.44 mL), and the resulting mixture was stirred at
room temperature. After 3 h, the reaction was quenched with satd
aq NH4Cl, and the mixture was extracted with AcOEt. The organic
layer was washed with brine, dried over Na2SO4, and then con-
centrated in vacuo. The obtained residue was purified by flash
column chromatography (SiO2, hexane/Et2O¼2/1) to give 2b
(28.6 mg, 98% yield) as colorless oil.
n
d
2.54 (dd, J¼6.0, 13.2 Hz, 1H),
2.75 (d, J¼15.2 Hz, 1H), 2.83 (dd, J¼6.0, 13.2 Hz, 1H), 2.89 (d,
J¼15.2 Hz, 1H), 3.14e3.20 (m, 1H), 3.84 (s, 3H), 3.85 (s, 3H),
4.63e4.85 (m, 3H), 6.40 (d, J¼10.0 Hz, 1H), 7.01 (d, J¼10.0 Hz, 1H),
7.38e7.43 (m, 2H), 7.57 (ddd, J¼1.6, 7.2, 8.0 Hz, 1H), 8.14 (dd, J¼1.2,
8.0 Hz, 1H); 13C NMR (CDCl3, major diastereomer):
d 39.3, 45.6, 51.9,
53.1, 53.2, 54.7, 60.2, 117.9, 126.6, 126.7, 127.1, 132.1, 132.3, 133.3,
154.8, 155.0, 171.6, 172.7, 184.8; ESI-LRMS m/z 363 (MþNaþ); ESI-
HRMS Calcd for C20H20NaO5 (MþNaþ): 363.1208. Found: 363.1184.
4.3.2. Dimethyl 6-hydroxy-4-vinyl-3,4-dihydronaphthalene-2,2(1H)-
dicarboxylate (2a). Colorless solid; mp 113e115 ꢀC; IR (ATR)
n
3443,
2954, 1721, 1611, 1500, 1436, 1274, 1226, 1056, 1031, 988, 919, 886,
817 cmꢁ1 1H NMR (CDCl3):
4.2.8. (E)-Dimethyl 6-methyl-8-oxo-4-(prop-1-enyl)spiro[4.5]deca-
;
d
1.98 (dd, J¼11.2, 13.6 Hz, 1H), 2.57
6,9-diene-2,2-dicarboxylate (1g). Yellow oil; IR (ATR)
1665, 1625, 1436, 1255, 1200,1095, 966, 859 cmꢁ1; 1H NMR (CDCl3):
1.56e1.58 (m, 3H), 2.42 (d, J¼14.8 Hz, 1H), 2.50 (dd, J¼14.0,
n
2959, 1732,
(ddd, J¼2.0, 6.0, 13.6 Hz, 1H), 3.09 (d, J¼15.6 Hz,1H), 3.33 (dd, J¼2.0,
15.6 Hz, 1H), 3.41e3.48 (m, 1H), 3.69 (s, 3H), 3.74 (s, 3H), 4.96 (s,
1H), 5.15e5.20 (m, 2H), 5.72 (ddd, J¼6.8, 10.0, 17.2 Hz, 1H), 6.62 (dd,
d

9614
M. Yoshida et al. / Tetrahedron 69 (2013) 9609e9615
J¼2.8, 8.0 Hz, 1H), 6.63 (d, J¼2.8 Hz, 1H), 6.98 (d, J¼8.0 Hz, 1H); 13
C
1722, 1628, 1600, 1519, 1434, 1394, 1341, 1260, 1228, 1087, 921, 861,
760 cmꢁ1; 1H NMR (CDCl3):
NMR (CDCl3):
d
34.3, 34.9, 41.4, 52.7, 52.8, 53.6, 114.0, 114.8, 116.7,
d
2.07 (dd, J¼11.2,13.6 Hz,1H), 2.66 (ddd,
125.2, 129.9, 137.5, 140.9, 154.0, 171.3, 172.1; ESI-LRMS m/z 313
(MþNaþ); ESI-HRMS Calcd for C16H18NaO5 (MþNaþ): 313.1052.
Found: 313.1005. The enantiomeric excess was determined by
chiral HPLC analysis (DAICEL CHIRALPAK AD-H, hexane/2-
J¼2.0, 6.0,13.6 Hz, 1H), 3.32 (dd, J¼2.0, 16.4 Hz, 1H), 3.62 (ddd, J¼6.0,
8.8,11.2 Hz, 1H), 3.66 (s, 3H), 3.80 (s, 3H), 3.87 (d, J¼16.4 Hz, 1H), 5.18
(s, 1H), 5.19 (dd, J¼1.2, 9.6 Hz, 1H), 5.24 (dd, J¼1.2, 16.8 Hz, 1H), 5.72
(ddd, J¼8.8, 9.6,16.8 Hz,1H), 6.65 (s,1H), 7.48 (ddd, J¼0.8, 8.4, 8.4 Hz,
1H), 7.55 (ddd, J¼0.8, 8.4, 8.4 Hz, 1H), 7.98 (d, J¼8.4 Hz, 1H), 8.16 (dd,
propanol¼90/10, flow rate: 1.0 mL/min, 35 ꢀC, tR 10.0 min [minor-
24
isomer] and 16.6 min [major-isomer], detection at 254 nm); [
a
]
J¼0.8, 8.4 Hz,1H); 13C NMR (CDCl3):
d 30.9, 34.6, 42.0, 52.8, 52.9, 53.4,
108.9, 116.8, 120.7, 122.1, 123.0, 123.7, 124.8, 126.7, 133.0, 133.5, 141.5,
D
þ13.0 (c 0.87, CHCl3, 65% ee).
149.8, 171.4, 172.4; ESI-LRMS m/z 363 (MþNaþ); ESI-HRMS Calcd for
4. 3. 3. Dimethyl 6-hydroxy-5, 7-dimethyl-4-vinyl-3, 4-
dihydronaphthalene-2,2(1H)-dicarboxylate (2b). Colorless oil; IR
C
20H20NaO5 (MþNaþ): 363.1208. Found: 363.1189.
(ATR)
n
3502, 2953, 1727, 1636, 1481, 1435, 1249, 1208, 1078, 1053,
4 . 3 . 8 . ( E ) - D i m e t h yl 6 - hy d ro x y - 4 - ( p ro p - 1 - e nyl ) - 3 , 4 -
dihydronaphthalene-2,2(1H)-dicarboxylate (2g). Colorless solid;
921 cmꢁ1
;
1H NMR (CDCl3):
d
2.06 (s, 3H), 2.20 (s, 3H), 2.33 (ddd,
J¼1.6, 4.4, 14.0 Hz, 1H), 2.54 (ddd, J¼1.6, 7.2, 14.0 Hz, 1H), 2.98 (d,
J¼16.0 Hz, 1H), 3.31 (d, J¼16.0 Hz, 1H), 3.65 (s, 3H), 3.66 (s, 3H), 3.77
(ddd, J¼4.4, 6.4, 7.2 Hz, 1H), 4.65 (s, 1H), 4.68 (ddd, J¼1.6, 1.6,
17.6 Hz, 1H), 4.98 (ddd, J¼1.6, 1.6, 10.4 Hz, 1H), 5.73 (ddd, J¼6.4, 10.4,
mp 88e92 ꢀC; IR (ATR)
n
3461, 2954, 1733, 1611, 1500, 1448, 1273,
1227, 1068, 968, 815 cmꢁ1 1H NMR (CDCl3):
;
d
1.72 (dd, J¼1.6,
6.0 Hz, 3H), 1.95 (dd, J¼11.2, 13.6 Hz, 1H), 2.53 (ddd, J¼2.0, 6.0,
13.6 Hz, 1H), 3.07 (d, J¼16.0 Hz, 1H), 3.32 (dd, J¼2.0, 16.0 Hz, 1H),
3.37 (ddd, J¼6.0, 8.8, 11.2 Hz, 1H), 3.68 (s, 3H), 3.74 (s, 3H), 5.21 (s,
1H), 5.31e5.37 (m, 1H), 5.60 (dq, J¼15.2, 6.0 Hz, 1H), 6.59 (dd, J¼2.8,
8.4 Hz, 1H), 6.63 (d, J¼2.8 Hz, 1H), 6.95 (d, J¼8.4 Hz, 1H); 13C NMR
17.6 Hz, 1H), 6.79 (s, 1H); 13C NMR (CDCl3):
d 11.9, 15.8, 34.8, 34.8,
38.5, 52.3, 52.6, 52.6, 114.9, 121.6, 121.9, 125.5, 128.4, 132.7, 140.6,
150.8, 171.9, 172.0; ESI-LRMS m/z 341 (MþNaþ); ESI-HRMS Calcd for
C
18H22NaO5 (MþNaþ): 341.1365. Found: 341.1323.
(CDCl3): d 17.8, 34.3, 35.4, 40.2, 52.7, 52.8, 53.7, 113.8, 114.8, 125.1,
127.4, 129.8, 133.7, 138.5, 154.0, 171.5, 172.3; ESI-LRMS m/z 327
(MþNaþ); ESI-HRMS Calcd for C17H20NaO5 (MþNaþ): 327.1208.
Found: 327.1169.
4.3.4. Dimethyl 6-hydroxy-5,7-dimethoxy-4-vinyl-3,4-
dihydronaphthalene-2,2(1H)-dicarboxylate (2c). White solid; mp
94e96 ꢀC; IR (ATR)
n
3460, 2952, 2843, 1730, 1615, 1498, 1448, 1433,
1294, 1245, 1198, 1124, 1095, 1072, 1002, 915, 882, 827 cmꢁ1 1H
NMR (CDCl3):
;
4.3.9. (E)-Dimethyl
2,2(1H)-dicarboxylate (2h). White solid; mp 130e132 ꢀC; IR (ATR)
3444, 3024, 2953, 1720, 1610, 1498, 1446, 1268, 1225, 1073, 967,
817, 738, 694 cmꢁ1 1H NMR (CDCl3):
6-hydroxy-4-styryl-3,4-dihydronaphthalene-
d
2.23 (dd, J¼6.4, 14.0 Hz, 1H), 2.51 (ddd, J¼1.6, 7.2,
14.0 Hz, 1H), 3.05 (d, J¼15.6 Hz, 1H), 3.27 (d, J¼15.6 Hz, 1H), 3.66 (s,
3H), 3.68 (s, 3H), 3.79 (s, 3H), 3.83e3.86 (m, 1H), 3.86 (s, 3H), 4.83
(ddd, J¼1.6, 1.6, 17.2 Hz, 1H), 4.99 (ddd, J¼1.6, 1.6, 10.4 Hz, 1H), 5.41
(s, 1H), 5.82 (ddd, J¼6.8, 10.4, 17.2 Hz, 1H), 6.44 (s, 1H); 13C NMR
n
;
d
2.06 (dd, J¼11.2, 13.6 Hz,
1H), 2.63 (ddd, J¼2.0, 6.0, 13.6 Hz, 1H), 3.13 (d, J¼16.4 Hz, 1H),
3.36 (dd, J¼2.0, 16.4 Hz, 1H), 3.62 (ddd, J¼6.0, 8.8, 11.2 Hz, 1H),
3.68 (s, 3H), 3.72 (s, 3H), 4.96 (s, 1H), 6.11 (dd, J¼8.8, 15.6 Hz, 1H),
6.51 (d, J¼15.6 Hz, 1H), 6.63e6.65 (m, 2H), 7.01 (d, J¼8.4 Hz, 1H),
7.23 (t, J¼7.2 Hz, 1H), 7.31 (dd, J¼7.2, 7.2 Hz, 2H), 7.37 (d, J¼7.2 Hz,
(CDCl3):
d 34.5, 34.8, 35.9, 52.4, 52.6, 53.0, 56.0, 60.2, 106.2, 113.7,
122.3, 124.9, 137.0, 141.7, 145.2,146.4, 171.6, 171.9; ESI-LRMS m/z 373
(MþNaþ); ESI-HRMS Calcd for C18H22NaO7 (MþNaþ): 373.1263.
Found: 373.1229.
2H); 13C NMR (CDCl3):
d 34.2, 35.1, 40.6, 52.8, 52.9, 53.6, 114.1,
115.0, 125.2, 126.2 (2C), 127.4, 128.6 (2C), 130.1, 131.9, 132.4,
137.0, 137.7, 154.1, 171.3, 172.1; ESI-LRMS m/z 389 (MþNaþ);
ESI-HRMS Calcd for C22H22NaO5 (MþNaþ): 389.1365. Found:
389.1327.
4 . 3 . 5 . D i m e t h y l 6 - h y d r o x y - 8 - m e t h y l - 4 - v i n y l - 3 , 4 -
dihydronaphthalene-2,2(1H)-dicarboxylate (2d). Colorless solid;
mp 126e129 ꢀC; IR (ATR)
n
3460, 2953, 2925, 2854,1721,1612,1596,
1435, 1243,1197, 1147, 1084, 1034, 996, 920, 858, 687 cmꢁ1; 1H NMR
(CDCl3):
d
2.00 (dd, J¼11.2, 13.6 Hz, 1H), 2.21 (s, 3H), 2.53 (ddd,
4 . 3 .10 . D i m e t h y l 6 - h y d r o x y - 4 - ( 1 - p h e n y l v i n y l ) - 3 , 4 -
dihydronaphthalene-2,2(1H)-dicarboxylate (2i). Colorless oil; IR
J¼2.0, 5.6, 13.6 Hz, 1H), 2.84 (d, J¼16.4 Hz, 1H), 3.30 (d, J¼16.4 Hz,
1H), 3.38 (ddd, J¼5.6, 8.8, 11.2 Hz, 1H), 3.70 (s, 3H), 3.76 (s, 3H), 5.11
(s, 1H), 5.14 (d, J¼9.6 Hz, 1H), 5.15 (d, J¼17.2 Hz, 1H), 5.70 (ddd,
(ATR)
n
3446, 3024, 2953, 1720, 1610, 1499, 1435, 1266, 1224, 1078,
1056, 1030, 907, 820, 780, 735, 702 cmꢁ1
;
1H NMR (CDCl3):
d
2.06
J¼8.8, 9.6, 17.2 Hz, 1H), 6.50 (s, 2H); 13C NMR (CDCl3):
d
19.8, 31.5,
(dd, J¼10.8, 13.6 Hz, 1H), 2.62 (ddd, J¼2.0, 6.4, 13.6 Hz, 1H), 3.15 (d,
J¼16.0 Hz,1H), 3.33 (dd, J¼2.0,16.0 Hz,1H), 3.66 (s, 3H), 3.69 (s, 3H),
4.11 (dd, J¼6.4, 10.8 Hz, 1H), 4.89 (s, 1H), 5.09 (s, 1H), 5.45 (s, 1H),
6.65 (dd, J¼2.4, 8.4 Hz, 1H), 6.74 (d, J¼2.4 Hz, 1H), 7.01 (d, J¼8.4 Hz,
34.5, 41.6, 52.8, 52.8, 53.5, 112.5, 115.6, 116.5, 123.8, 137.5, 137.8,
141.1, 153.5, 171.6, 172.4; ESI-LRMS m/z 327 (MþNaþ); ESI-HRMS
Calcd for C17H20NaO5 (MþNaþ): 327.1208. Found: 327.1168.
1H), 7.22e7.27 (m, 5H); 13C NMR (CDCl3):
d 34.4, 34.6, 43.4, 52.7,
4 . 3 . 6 . D i m e t h y l 6 - h y d r o x y - 8 - m e t h o x y - 4 - v i n y l - 3 , 4 -
52.8, 54.0, 114.1, 114.9, 116.5, 125.8, 126.8 (2C), 127.5, 128.3 (2C),
130.1, 138.2, 140.6, 151.2, 154.2, 171.3, 172.0; ESI-LRMS m/z 389
(MþNaþ); ESI-HRMS Calcd for C22H22NaO5 (MþNaþ): 389.1365.
Found: 389.1345.
dihydronaphthalene-2,2(1H)-dicarboxylate (2e). White solid; mp
114e118 ꢀC; IR (ATR)
n
3450, 2954, 1732, 1605, 1435, 1248, 1195,
1148, 1109, 1055, 977, 923, 843 cmꢁ1 1H NMR (CDCl3):
;
d
1.98 (dd,
J¼11.2, 13.2 Hz, 1H), 2.51 (ddd, J¼2.0, 6.0, 13.2 Hz, 1H), 2.76 (dd,
J¼1.2, 16.8 Hz,1H), 3.35 (ddd, J¼6.0, 8.8,11.2 Hz,1H), 3.46 (dd, J¼2.0,
16.8 Hz, 1H), 3.70 (s, 3H), 3.75 (s, 3H), 3.77 (s, 3H), 5.14 (d, J¼9.6 Hz,
1H), 5.15 (s, 1H), 5.15 (d, J¼18.0 Hz, 1H), 5.68 (ddd, J¼8.8, 9.6,
18.0 Hz, 1H), 6.23 (d, J¼1.6 Hz, 1H), 6.24 (d, J¼1.6 Hz, 1H); 13C NMR
4.3.11. Di-tert-butyl
2,2(1H)-dicarboxylate (2j). White solid; mp 152e154 ꢀC; IR (ATR)
3448, 2977, 2932, 1712, 1611, 1500, 1455, 1393, 1368, 1278, 1234,
1150, 1053, 915, 846 cmꢁ1 1H NMR (CDCl3):
1.37 (s, 9H), 1.46 (s,
6-hydroxy-4-vinyl-3,4-dihydronaphthalene-
n
;
d
(CDCl3):
d
28.4, 34.5, 41.3, 52.7, 52.8, 52.9, 55.4, 96.9, 106.4, 114.3,
9H), 1.88 (dd, J¼11.6, 13.6 Hz, 1H), 2.45 (ddd, J¼2.0, 6.4, 13.6 Hz, 1H),
2.94 (d, J¼16.0 Hz, 1H), 3.23 (dd, J¼2.0, 16.0 Hz, 1H), 3.42 (ddd,
J¼6.4, 8.8, 11.6 Hz, 1H), 4.97 (s, 1H), 5.15 (dd, J¼2.0, 10.0 Hz, 1H), 5.17
(dd, J¼2.0, 16.8 Hz, 1H), 5.74 (ddd, J¼8.8, 10.0, 16.8 Hz, 1H), 6.60 (dd,
116.5, 138.0, 141.0, 154.5, 158.1, 171.6, 172.5; ESI-LRMS m/z 343
(MþNaþ); ESI-HRMS Calcd for C17H20NaO6 (MþNaþ): 343.1158.
Found: 343.1128.
J¼2.4, 8.0 Hz, 1H), 6.62 (d, J¼2.4 Hz, 1H), 6.97 (d, J¼8.0 Hz, 1H); 13
C
4.3.7. Dimethyl 9-hydroxy-1-vinyl-1,2-dihydrophenanthrene-3,3(4H)-
NMR (CDCl3): d 27.7 (3C), 27.8 (3C), 34.4, 35.0, 41.8, 54.8, 81.2, 81.6,
dicarboxylate (2f). White solid; IR (ATR)
n
3446, 2953, 2924, 2853,
113.8, 114.6, 116.3, 125.9, 129.8, 138.0, 141.3, 153.9, 170.1, 171.1;

M. Yoshida et al. / Tetrahedron 69 (2013) 9609e9615
9615
ESI-LRMS m/z 397 (MþNaþ); ESI-HRMS Calcd for C22H30NaO5
(MþNaþ): 397.1991. Found: 397.1986.
2. For representative reviews on transition metal-catalyzed cross-coupling re-
actions, see: (a) Suzuki, A. Angew. Chem., Int. Ed. 2011, 50, 6722e6737; (b)
Negishi, E. Angew. Chem., Int. Ed. 2011, 50, 6738e6764; (c) Johansson Seechurn,
C. C. C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem., Int. Ed. 2012, 51,
5062e5085.
4.4. Spirocyclizationedienoneephenol rearrangement
cascade
3. For reviews on h
6-arene metal complex-mediated reactions, see: (a) Semmel-
hack, M. F. In Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, F. G.
A., Wilkinson, G., Eds.; Pergamon: Oxford, UK, 1995; pp 979e1015; (b) Sem-
melhack, M. F.; Chlenov, A. In Transition Metal Arene
p-Complexes in Organic
4.4.1. Experimental procedure for the one-pot sequential multi-
catalytic process. Compound 3b (31.5 mg, 0.080 mmol), Pd(dba)2
(2.3 mg, 4.0 mmol), and PPh3 (2.5 mg, 9.6 mmol) were dissolved in
€
Synthesis and Catalysis; Kundig, E. P., Ed.; Springer: Berlin, Germany, 2004;
ꢀ
pp 21e69; (c) Rosillo, M.; Domínguez, G.; Perez-Castells, J. Chem. Soc. Rev. 2007,
36, 1589e1604.
CH3CN (0.40 mL), and the resulting mixture was stirred at room
temperature. After 9 h, Sc(OTf)3 (7.9 mg, 0.016 mmol) was added,
and the reaction was stirred for another 30 min. The reaction was
quenched with satd aq NH4Cl, and the mixture was extracted with
AcOEt. The organic layer was washed with brine, dried over Na2SO4,
and then concentrated in vacuo. The obtained residue was purified
by flash column chromatography (SiO2, hexane/Et2O¼2/1) to give
2b (24.1 mg, 93% yield) as colorless oil.
4. For representative reviews on transition-metal-catalyzed CꢁH bond function-
alization, see: (a) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed.
2009, 48, 9792e9826; (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110,
1147e1169; (c) Satoh, T.; Miura, M. Chem.dEur. J. 2010, 16, 11212e11222; (d)
Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem., Int. Ed.
2012, 51, 10236e10254 and references cited therein.
5. For a review on recent developments in the FriedeleCrafts alkylation, see: (a)
Rueping, M.; Nachtsheim, B. J. Beilstein J. Org. Chem. 2010, 6 No. 6.
6. For examples of meta-selective functionalization of electron-rich arenes, see:
(a) Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593e1597; (b) Kawakami, Y.;
Kabe, Y. Chem. Lett. 2010, 39, 1082e1083; (c) Duong, H. A.; Gilligan, R. E.; Cooke,
M. L.; Phipps, R. J.; Gaunt, M. J. Angew. Chem., Int. Ed. 2011, 50, 9429e9432; (d)
Cornella, J.; Righi, M.; Larrosa, I. Angew. Chem., Int. Ed. 2011, 50, 463e466; (e)
Leow, D.; Li, G.; Mei, T.-S.; Yu, J.-Q. Nature 2012, 486, 518e522; (f) Robbins, D.
W.; Hartwig, J. F. Angew. Chem., Int. Ed. 2013, 52, 933e937.
4.4.2. Typical experimental procedure for the sequential reaction
with a single-catalyst. Compound 4h (30.7 mg, 0.080 mmol), and
Ph3CClO4 (1.4 mg, 4.0 mmol) were dissolved in CH3NO2 (0.40 mL),
and the resulting mixture was stirred at room temperature. After
3 h, the reaction was quenched with water, and the mixture was
extracted with AcOEt. The organic layer was washed with brine,
dried over Na2SO4, and then concentrated in vacuo. The obtained
residue was purified by flash column chromatography (SiO2, hex-
ane/AcOEt¼3/1) to give 2h (24.8 mg, 85% yield) as colorless oil.
7. (a) Nemoto, T.; Ishige, Y.; Yoshida, M.; Kohno, Y.; Kanematsu, M.; Hamada, Y.
Org. Lett. 2010, 12, 5020e5023; (b) Yoshida, M.; Nemoto, T.; Zhao, Z.; Ishige, Y.;
Hamada, Y. Tetrahedron: Asymmetry 2012, 23, 859e866; (c) Nemoto, T.; Zhao, Z.;
Yokosaka, T.; Suzuki, Y.; Wu, R.; Hamada, Y. Angew. Chem., Int. Ed. 2013, 52,
2217e2220; (d) Nemoto, T.; Nozaki, T.; Yoshida, M.; Hamada, Y. Adv. Synth.
Catal., 2013, 355, 2693e2700.
8. For a review on dienone-ephenol rearrangement, see: (a) Miller, B. Acc. Chem.
Res. 1975, 8, 245e256 For recent examples of dienoneephenol rearrangement
of spirocyclohexadienones or spiro-type intermediates, see: (b) Moisan, L.;
Wagner, M.; Comesse, S.; Doris, E. Tetrahedron Lett. 2006, 47, 9093e9094; (c)
4.4.3. Dimethyl
malonate (4a). Colorless oil; IR (ATR)
1614, 1516, 1438, 1201, 1174, 1110, 1049, 975, 841 cmꢁ1
(CDCl3):
2.55 (d, J¼7.2 Hz, 2H), 3.16 (s, 2H), 3.71 (s, 3H), 3.72 (s,
2-(4-hydroxybenzyl)-2-(4-hydroxybut-2-en-1-yl)
3443, 3024, 2952, 1720,
1H NMR
€
Hata, K.; Hamamoto, H.; Shiozaki, Y.; Cammerer, S. B.; Kita, Y. Tetrahedron 2007,
63, 4052e4060; (d) Sauer, A. M.; Crowe, W. E.; Henderson, G.; Laine, R. A.
Tetrahedron Lett. 2007, 48, 6590e6593.
n
;
9. (a) Ishikawa, H.; Suzuki, T.; Hayashi, Y. Angew. Chem., Int. Ed. 2009, 48,
1304e1307; (b) Ishikawa, H.; Honma, M.; Hayashi, Y. Angew. Chem., Int. Ed. 2011,
50, 2824e2827; (c) Hayashi, Y.; Umemiya, S. Angew. Chem., Int. Ed. 2013, 52,
3450e3452; (d) For a review, see: Vaxelaire, C.; Winter, P.; Christmann, M.
Angew. Chem., Int. Ed. 2011, 50, 3605e3607.
10. For representative examples of Sc catalysis in aqueous media, see: (a) Ishikawa,
S.; Hamada, T.; Manabe, K.; Kobayashi, S. J. Am. Chem. Soc. 2004, 126,
12236e12237; (b) Kokubo, M.; Ogawa, C.; Kobayashi, S. Angew. Chem., Int. Ed.
2008, 47, 6909e6911; (c) Ueno, M.; Kitanosono, T.; Sakai, M.; Kobayashi, S. Org.
Biomol. Chem. 2011, 9, 3619e3621; (d) Kitanosono, T.; Sakai, M.; Ueno, M.;
Kobayashi, S. Org. Biomol. Chem. 2012, 10, 7134e7147.
d
3H), 4.12 (d, J¼5.6 Hz, 2H), 5.63 (dt, J¼15.6, 7.2 Hz, 1H), 5.75 (dt,
J¼15.6, 5.6 Hz, 1H), 6.71 (d, J¼8.0 Hz, 2H), 6.93 (d, J¼8.0 Hz, 2H); 13
C
NMR (CDCl3):
d 34.9, 37.4, 52.4 (2C), 59.3, 63.3, 115.3 (2C), 126.2,
127.4, 131.0 (2C), 133.8, 154.9, 171.4 (2C); ESI-LRMS m/z 331
(MþNaþ); ESI-HRMS Calcd for C16H20NaO6 (MþNaþ): 331.1158.
Found: 331.1140.
11. When Sc(OTf)3 was used as a Lewis acid catalyst, decarboxylative removal of
one of the tert-butyl esters occurred, resulting in low isolated yield. Product 2j
was obtained in 76% yield using AuCl3 as a Lewis acid catalyst.
12. Optically active 1a (66% ee) was prepared from the corresponding linear
starting material using 3 mol % of Pd(dba)2 and 3.6 mol % of (R,R)-ANDEN-
phenyl-Trost ligand in CH3CN at room temperature (24 h, 58% yield).
13. Compound 1a can be synthesized in high yield with excellent enantiomeric
excess (97% ee) using the chiral Ir catalyst system developed by You, et al. See:
Wu, Q.-F.; Liu, W.-B.; Zhuo, C.-X.; Rong, Z.-Q.; Ye, K.-Y.; You, S.-L. Angew. Chem.,
Int. Ed. 2011, 50, 4455e4458.
14. Our preceding paper relating to the one-pot sequential multi-catalytic process,
see: Nemoto, T.; Fukuda, T.; Hamada, Y. Tetrahedron Lett. 2006, 47, 4365e4368.
15. You and his co-workers recently reported the synthesis of fused indole de-
rivatives through a reaction sequence: dearomatization of indoles using an Ir-
catalyzed asymmetric allylic alkylation and stereospecific migration. See: (a)
Wu, Q.-F.; Zheng, C.; You, S.-L. Angew. Chem., Int. Ed. 2012, 51, 1680e1683; (b)
Zheng, C.; Wu, Q.-F.; You, S.-L. J. Org. Chem. 2013, 78, 4357e4365; (c) Zhuo, C.-X.;
Wu, Q.-F.; Zhao, Q.; Xu, Q.-L.; You, S.-L. J. Am. Chem. Soc. 2013, 135, 8169e8172.
16. For examples of the FriedeleCrafts-type cyclization of phenol derivatives via
a catalytic activation of allylic alcohols, see: (a) Namba, K.; Yamamoto, H.; Sa-
saki, I.; Mori, K.; Imagawa, H.; Nishizawa, M. Org. Lett. 2008, 10, 1767e1770; (b)
Zheng, H.; Ghanbari, S.; Nakamura, S.; Hall, D. G. Angew. Chem., Int. Ed. 2012, 51,
6187e6190; (c) Schaforth, M. A.; Sarlah, D.; Krautwald, S.; Carreira, E. M. J. Am.
Chem. Soc. 2012, 134, 20276e20278; (d) Yokosaka, T.; Nemoto, T.; Hamada, Y.
Tetrahedron Lett. 2013, 54, 1562e1565.
4.4.4. (E)-Dimethyl 2-(4-hydroxy-4-phenylbut-2-en-1-yl)-2-(4-hy-
droxybenzyl)malonate (4h). White solid; mp 101e103 ꢀC; IR (ATR)
n
3443, 3033, 2952, 1719, 1614, 1515, 1437, 1200, 1173, 1109, 1047, 971,
840, 735, 700 cmꢁ1; 1H NMR (CDCl3):
d
2.36 (s, 1H), 2.52e2.54 (m,
2H), 3.15 (s, 2H), 3.62 (s, 3H), 3.63 (s, 3H), 5.17 (s, 1H), 5.72e5.75 (m,
3H), 6.65 (d, J¼8.0 Hz, 2H), 6.87 (d, J¼8.0 Hz, 2H), 7.24e7.35 (m,
5H); 13C NMR (CDCl3):
d 34.9, 37.6, 52.4 (2C), 59.3, 74.8, 115.2 (2C),
125.3, 126.1 (2C), 127.3, 127.7, 128.5 (2C), 131.0 (2C), 137.1, 142.6,
154.9, 171.3, 171.4; ESI-LRMS m/z 407 (MþNaþ); ESI-HRMS Calcd for
C
22H24NaO6 (MþNaþ): 407.1471. Found: 407.1484.
Acknowledgements
This work was supported by a Grant-in Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science, and
Technology, Japan, the Research Foundation for Pharmaceutical
Sciences, and Chiba university.
Supplementary data
17. For examples of the same g-lactonization using Au catalyst, see: (a) Wang, Y.-
H.; Zhu, L.-L.; Zhang, Y.-X.; Chen, Z. Chem. Commun. 2010, 577e579; (b)
Chiarucci, M.; Locritani, M.; Cera, G.; Bandini, M. Beilstein J. Org. Chem. 2011, 7,
1198e1204.
Supplementary data (1H and 13C NMR charts of the reported
compounds) can be found. Supplementary data related to this ar-
ticle can be found at http://dx.doi.org/10.1016/j.tet.2013.09.042.
18. Compound 1a was smoothly transformed into 2a in 86% yield by treating with
Ph3CClO4 in CH3NO2. This result reasonably supports our mechanistic hy-
pothesis shown in Scheme 4. On the other hand, spirocyclic intermediates 1a
and 1h could not be detected in these examinations (monitored by TLC). This
would be due to rapid consumption of the spirocyclic intermediates under the
cascade reaction conditions.
References and notes
1. For a review, see: Snieckus, V. Chem. Rev. 1990, 90, 879e933.