Palladium-catalyzed intramolecular ipso-friedel-crafts allylic alkylation of phenols via arylative activation of allenes

Article abstract of DOI:10.1002/adsc.201300326

A novel and efficient synthetic method for functionalized spiro[4.5]cyclohexadienones was developed based on the palladium-catalyzed sequential process: Heck insertion to an allene-intramolecular ipso-Friedel-Crafts allylic alkylation cascade. Using 5 mol% of palladium catalyst, a wide variety of spirocycles was obtained in good to excellent yields. The developed cascade process was also applicable to the synthesis of tetrahydronaphthalene derivatives. Copyright

Full text of DOI:10.1002/adsc.201300326

UPDATES
DOI: 10.1002/adsc.201300326
Palladium-Catalyzed Intramolecular ipso-Friedel–Crafts Allylic
Alkylation of Phenols via Arylative Activation of Allenes
Tetsuhiro Nemoto,a Tomoyuki Nozaki,a Mariko Yoshida,a
and Yasumasa Hamadaa,*
a
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan
Fax : (+81)-43-226-2920; e-mail: hamada@p.chiba-u.ac.jp
Received: April 18, 2013; Revised: June 17, 2013; Published online: September 5, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300326.
Abstract: A novel and efficient synthetic method
for functionalized spiroACTHNURGTNE[UNG 4.5]cyclohexadienones was
developed based on the palladium-catalyzed se-
quential process: Heck insertion to an allene–intra-
molecular ipso-Friedel–Crafts allylic alkylation cas-
cade. Using 5 mol% of palladium catalyst, a wide
variety of spirocycles was obtained in good to excel-
lent yields. The developed cascade process was also
applicable to the synthesis of tetrahydronaphtha-
lene derivatives.
Scheme 1. Pd-catalyzed intramolecular ipso-Friedel–Crafts
allylic alkylation of phenols.
ety of spiroACTHNUGRTNEUNG[4.5]cyclohexadienones using this catalytic
reaction system. We developed a reaction system to
overcome this drawback. Herein we report a novel
Keywords: allylic substitution; cascade reactions;
palladium; spiro compounds; synthetic methods
synthetic
method
for
functionalized
spiro-
AHCTUNGTREG[NNUN 4.5]cyclohexadienones through a Pd-catalyzed se-
quential process: Heck insertion to an allene–intra-
molecular ipso-Friedel–Crafts allylic alkylation cas-
cade.
The efficient construction of spirocyclic frameworks is
Aryl halides generally react with an allenyl sub-
an important topic in synthetic organic chemistry due strate in the presence of a Pd(0) catalyst to give a 2-
to their broad distribution in biologically active natu- aryl p-allylpalladium(II) species through a Heck inser-
ral products and pharmaceuticals. Among the various tion process.[6] We envisioned that if this type of Heck
spirocycles, spirocyclohexadienones are one of the insertion and an intramolecular ipso-Friedel–Crafts
most important classes of compounds in organic syn- allylic alkylation of phenols proceeded sequentially in
thesis.[1] Functionalization of the cyclohexadienone the presence of
a Pd catalyst, various spiro-
unit provides an efficient and rapid access to multicy-
ACHTUNGTREN[NUGN 4.5]cyclohexadienones with a 1-arylvinyl substituent
clic molecular frameworks,[2] indicating its potential on the vicinal carbon to the spirocenter could be syn-
utility in complex molecule syntheses. Extensive thesized from a single allenyl substrate (Scheme 2).[7]
effort has therefore focused on the development of an
efficient method for synthesizing this structural conditions using allenyl substrate 1 and iodobenzene
motif.[3]
as substrates (Table 1). We first examined the reaction
As part of our ongoing studies aimed at developing using 5 mol% of Pd(dba)2, 12 mol% of PPh3, and
Based on this hypothesis, we optimized the reaction
AHCTUNGTRENNUNG
novel synthetic methods based on intramolecular 4 equiv. of K2CO3 at 708C in several solvent systems.
ipso-Friedel–Crafts-type reactions,[4] we recently re- The desired product 2a was obtained in 53% yield
ported a Pd-catalyzed intramolecular ipso-Friedel– when DMF was used as the solvent. Some by-prod-
1
Crafts allylic alkylation of phenols that provides ucts were detected in a H NMR analysis of the crude
spiroACHTUNGTRENNUNG[4.5]cyclohexadienones in excellent yield with sample and cyclic dimer 2a’, formed by an intermolec-
high diastereoselectivity under simple reaction condi- ular allylic etherification, was isolated as the major
tions (Scheme 1).[4a,5] Substrate preparation for this Pd byproduct (8% yield: 16% of 1 was incorporated)
catalysis, however, requires a long multi-step process, (entry 4). The concentration of the reaction dramati-
making it difficult to divergently produce a wide vari- cally affected the yield of 2a. When the reaction was
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Tetsuhiro Nemoto et al.
UPDATES
Table 1. Optimization of the reaction conditions using 1 and iodobenzene.
Entry
Solvent (conc.)
Temp. [8C]
Time [h]
Isolated yield [%]
1
2
3
4
5
6
7
8
9
THF (0.1 M)
toluene (0.1 M)
(CH2Cl)2 (0.1 M)
DMF (0.1 M)
DMF (0.05 M)
DMF (0.02 M)
DMF (0.01 M)
DMF (0.01 M)
DMF (0.01 M)
reflux
70
70
70
70
70
70
50
90
8
8
8
8
8
8
8
8
3
no reaction
no reaction
no reaction
2a (53), 2a’ (8)
2a (69), 2a’ (7)
2a (78), 2a’ (4)
2a (90), 2a’ (3)
no reaction
2a (94), 2a’ (2)
Table 2. Substrate scope: aryl iodides.
Scheme 2. Plan
for
the
synthesis
of
spiro-
ACHTUNGTRENNUNG
performed at 0.01M in DMF solution, 2a was ob-
tained in 90% yield, accompanied by the formation of
small amount of 2a’ (3% yield: 6% of 1 was incorpo-
rated) (entry 7). Furthermore, the reactivity increased
at a higher temperature and the desired spirocyclic
adduct was obtained in 94% yield (entry 9).
Having established the optimized conditions yield and 60% yield, respectively. Moreover, the reac-
(Table 1, entry 9), we next investigated the substrate tion using 2-iodonaphthalene proceeded smoothly
scope of the developed spirocyclization process. We under the same reaction conditions to give the spiro-
first examined reactions using substrate 1 and various cyclic adduct 2h in 83% yield. The generality of the
aryl iodides in the presence of 5 mol% of the catalyst allenyl substrates was investigated using iodobenzene
(Table 2). In addition to simple iodobenzene, para- as their partner (Table 3). ortho-Disubstituted phenol
substituted aryl iodides with an electron-withdrawing derivatives 3 and 5 reacted with iodobenzene under
group as well as an electron-donating group were ap- the optimized conditions and the corresponding prod-
plicable to this reaction, affording the spirocyclic ad- ucts 4 and 6 were obtained in excellent yields. When
ducts 2b–2e in a synthetically useful yield (70–87%). meta-substituted phenol derivative 7 was utilized as
Both meta- and ortho-substituted aryl iodide deriva- a substrate, a spirocyclic adduct with contiguous
tives were also suitable substrates for this process, af- chiral centers, 8, was produced in 90% yield with
fording the corresponding products 2f and 2g in 87% good diastereoselectivity (dr=6.5:1). The relative
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Palladium-Catalyzed Intramolecular ipso-Friedel–Crafts Allylic Alkylation of Phenols
Table 3. Substrate scope: allenyl compounds.[a]
Scheme 3. Synthesis of tetrahydronaphthalene derivatives.
in 86% yield [Scheme 3(b)]. Luche reduction of 8, fol-
lowed by treatment of the obtained alcohol inter-
mediate with TsOH in CH3CN, afforded the corre-
sponding bicyclic adduct 16 in 71% yield over two
steps [Scheme 3(c)]. The structures of 15 and 16 are
complementary to that of 14, demonstrating the syn-
thetic utility of the developed process.
In conclusion, we have developed a novel method
for synthesizing spiroACTHNUTRGNEU[GN 4.5]cyclohexadienone deriva-
tives using a Pd-catalyzed sequential process: Heck
insertion to an allene–intramolecular ipso-Friedel–
Crafts allylic alkylation cascade. Structurally diverse
[a]
Reaction
conditions:
Pd
(dba)2
(5 mol%),
PPh3
(12 mol%), iodobenzene (1.5 equiv.), K2CO3 (4 equiv.),
DMF (0.01M), 908C.
strereochemistry of the major isomer was determined spiroACHTUNTRGNEUNG[4.5]cyclohexadienones were obtained in good to
by NOE experiments. Although the diastereoselectiv- excellent yields under simple reaction conditions. Tet-
ity decreased, naphthol derivative 9 was also an appli- rahydronaphthalene derivatives were also accessible
cable substrate and the corresponding naphthoqui- based on the developed process.
none derivative 10 was obtained in 85% yield (dr=
1.2:1). In addition, when N-Ts-tethered allenyl sub-
strate 11 was used as a substrate, spirocyclic adduct Experimental Section
12 was obtained in 70% yield.[8]
Furthermore, the present cascade process was ap- General
plicable to the synthesis of tetrahydronaphthalene de-
rivatives (Scheme 3). When meta-substituted phenol
IR spectra were recorded on a JASCO FT/IR 230 Fourier
transform infrared spectrophotometer, equipped with ATR
derivative 13 was treated under the same reaction
conditions, Heck insertion to the allene, followed by
an intramolecular Friedel–Crafts allylic alkylation of
phenols,[9] proceeded sequentially to afford the prod-
uct with a tetrahydronaphthalene skeleton 14 in 97%
yield [Scheme 3(a)]. On the other hand, spirocyclic
adduct 8 could be converted into tetrahydronaphtha-
lene derivatives via acid-promoted skeletal rearrange-
ments. Dienone-phenol rearrangement of spirocyclo-
hexadienones is a useful method for synthesizing
functionalized phenol derivatives. Treatment of 8 with
0.5 equiv. of para-toluenesulfonic acid (TsOH) in
(Smiths Detection, DuraSample IR II). NMR spectra were
recorded on a JEOL ecs 400 spectrometer, operating at
400 MHz for 1H NMR, and 100 MHz for 13C NMR. ESI-
TOF mass spectra were measured on JEOL AccuTOF LC-
plus JMS-T100 LP. Reactions were carried out in dry solvent
under an argon atmosphere. Other reagents were purified
by the usual methods.
Synthesis of Allenyl Substrates
Malonate-tethered allenyl substrates 1, 3, 5, 7, 9, and 13
were prepared from dimethyl 2-(buta-2,3-dien-1-yl)malon-
AHCTUNGTRENNUNG
ate[10] and benzyl bromide derivatives according to the gen-
CH3CN provided the rearranged phenol derivative 15 eral procedure. N-Ts-tethered allenyl substrate 11 was pre-
Adv. Synth. Catal. 2013, 355, 2693 – 2700
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Tetsuhiro Nemoto et al.
UPDATES
pared from N-(buta-2,3-dien-1-yl)-4-methylbenzenesulfon-
2H), 3.27 (s, 2H), 3.70 (s, 6H), 4.67–4.70 (m, 2H), 5.05 (tt,
J=6.8, 7.6 Hz, 1H), 5.32 (s, 1H), 6.53 (dd, J=2.4, 8.4 Hz,
1H), 6.61 (d, J=2.4 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H);
13C NMR (CDCl3): d=19.9, 32.1, 33.8, 52.4 (2C), 59.2, 74.9,
84.7, 112.7, 117.2, 126.1, 131.3, 138.7, 154.3, 171.6 (2C),
209.9; HR-MS [(+)-ESI-TOF]: m/z=327.1200, calcd. for
ACHTUNGTRENNUNG
amide[11] and p-tert-butyldimethylsilyloxybenzyl bromide ac-
cording to the general procedure.
General Procedure
+
C17H20NaO5 (M+Na+): 327.1203.
To
yl)malon
a
stirred solution of dimethyl 2-(buta-2,3-dien-1-
ate (386.8 mg, 2.10 mmol) in THF (4 mL) at 08C
Dimethyl 2-(buta-2,3-dien-1-yl)-2-((4-hydroxynaphthalen-
1-yl)methyl)malonate (9): Pale brown solid; mp 112–1138C;
IR (ATR): n=3369, 2952, 1711, 1585, 1434, 1374, 1290,
ACHTUNGTRENNUNG
was added NaH (60% oil. 128.0 mg, 3.20 mmol), and the re-
sulting mixture was kept stirring for 30 min. p-tert-Butyldi-
methylsilyloxybenzyl bromide (747.5 mg, 2.50 mmol in 3 mL
of THF) was added to the reaction, and the reaction was
stirred for 1 h at room temperature. The reaction was
quenched with water, and the aqueous layer was extracted
with AcOEt. The combined organic layers were washed
with brine, dried over Na2SO4, and then evaporated under
vacuum. The obtained residue was purified by flash column
chromatography (SiO2, hexane/AcOEt=50/1 to 30/1) to
give the corresponding product; yield: 558.7 mg (66%).
To a stirred solution of the obtained product (558.7 mg,
1.38 mmol) and AcOH (0.16 mL, 2.80 mmol) in THF (7 mL)
at 08C was added TBAF (1M solution in THF, 2.8 mL,
2.80 mmol), and the resulting mixture was stirred for 1 h.
The reaction was quenched with saturated aqueous NH4Cl,
and the aqueous layer was extracted with AcOEt. The com-
bined organic layers were washed with brine, dried over
Na2SO4, and then evaporated under vacuum. The obtained
residue was purified by flash column chromatography (SiO2,
hexane/AcOEt=10/1 to 4/1) to give dimethyl 2-(buta-2,3-
dien-1-yl)-2-(4-hydroxybenzyl)malonate 1 as a colorless oil;
yield: 315.5 mg (79%). IR (ATR): n=3440, 1722, 1517,
1
1202, 1057, 835, 762, 736 cmÀ1; H NMR (CDCl3): d=2.63
(dt, J=7.2, 2.8 Hz, 2H), 3.59 (s, 6H), 3.72 (s, 2H), 4.71–4.74
(m, 2H), 5.09 (tt, J=6.8, 7.2 Hz, 1H), 5.91 (br-s, 1H), 6.62
(d, J=7.2 Hz, 1H), 7.16 (d, J=7.6 Hz, 1H), 7.42–7.49 (m,
2H), 7.98 (d, J=8.4 Hz, 1H), 8.19 (dd, J=1.2, 8.4 Hz, 1H);
13C NMR (CDCl3): d=32.1, 33.2, 52.4 (2C), 59.2, 75.0, 84.7,
107.9, 122.4, 123.6, 124.1, 124.6, 124.7, 126.2, 128.3, 133.7,
151.0, 171.6 (2C), 210.1; HR-MS [(+)-ESI-TOF]: m/z=
+
341.1372, calcd. for C18H22NaO5 (M+Na+): 341.1359.
N-(Buta-2,3-dien-1-yl)-N-(3-hydroxy-2-methylbenzyl)-4-
methylbenzenesulfonamide (11): White solid; mp 77–788C;
IR (ATR): n=3435, 1515, 1330, 1152, 1091, 815, 758,
1
659 cmÀ1; H NMR (CDCl3): d=2.44 (s, 3H), 3.76 (dt, J=
7.2, 2.4 Hz, 2H), 4.30 (s, 2H), 4.62 (dt, J=6.4, 2.4 Hz, 2H),
4.74 (tt, J=6.4, 7.2 Hz, 1H), 5.74 (s, 1H), 6.78 (d, J=8.0 Hz,
2H), 7.14 (d, J=8.4 Hz, 2H), 7.31 (d, J=8.0 Hz, 2H), 7.73
(d, J=8.4 Hz, 2H); 13C NMR (CDCl3): d=21.5, 45.2, 49.5,
76.1, 85.0, 115.4 (2C), 127.2 (2C), 127.6, 129.7 (2C), 130.1
(2C), 137.5, 143.4, 155.4, 209.5; HR-MS [(+)-ESI-TOF]:
m/z=352.0979, calcd. for C18H20NNaO3S+ (M+Na+):
352.0978.
Dimethyl
2-(buta-2,3-dien-1-yl)-2-(3-hydroxy-2-methyl-
1
1440, 1202, 847 cmÀ1; H NMR (CDCl3): d=2.53 (dt, J=7.6,
benzyl)malonate (13): Pale yellow solid; mp 80–828C; IR
(ATR): n=3445, 2952, 1718, 1586, 1435, 1200, 1072, 847,
2.4 Hz, 2H), 3.20 (s, 2H), 3.72 (s, 6H), 4.73 (dt, J=6.8,
2.4 Hz, 2H), 5.01 (tt, J=6.8, 7.6 Hz, 1H), 5.42 (s, 1H), 6.68–
6.71 (m, 2H), 6.93–6.96 (m, 2H); 13C NMR (CDCl3): d=
31.1, 37.1, 52.4 (2C), 59.2, 75.0, 84.4, 115.2 (2C), 127.5, 131.1
(2C), 154.8, 171.3 (2C), 210.1; HR-MS [(+)-ESI-TOF]:
1
779, 724 cmÀ1; H NMR (CDCl3): d=2.17 (s, 3H), 2.57 (dt,
J=7.6, 2.8 Hz, 2H), 3.37 (s, 2H), 3.70 (s, 6H), 4.68–4.71 (m,
2H), 4.70 (s, 1H), 5.06 (tt, J=6.8, 7.6 Hz, 1H), 6.65 (d, J=
8.4 Hz, 1H), 6.70 (d, J=7.6 Hz, 1H), 6.97 (dd, J=7.6,
8.4 Hz, 1H); 13C NMR (CDCl3): d=11.9, 31.9, 34.6, 52.4
(2C), 59.1, 74.9, 84.8, 113.5, 122.8, 123.8, 125.9, 135.8, 154.1,
171.4 (2C), 209.9; HR-MS [(+)-ESI-TOF]: m/z=313.1020,
+
m/z=313.1024, calcd. for C16H18NaO5 (M+Na+): 313.1046.
Dimethyl
2-(buta-2,3-dien-1-yl)-2-(4-hydroxy-3,5-dime-
thylbenzyl)malonate (3): White solid; mp 99–1018C; IR
(ATR): n=3522, 2951, 1728, 1490, 1435, 1201, 1153, 1075,
+
calcd. for C16H18NaO5 (M+Na+): 313.1046.
1
848 cmÀ1; H NMR (CDCl3): d=2.18 (s, 6H), 2.52 (dt, J=
8.0, 2.4 Hz, 2H), 3.14 (s, 2H), 3.72 (s, 6H), 4.55 (s, 1H), 4.73
(dt, J=6.8, 2.4 Hz, 2H), 5.01 (tt, J=6.8, 8.0 Hz, 1H), 6.69 (s,
2H); 13C NMR (CDCl3): d=15.9 (2C), 31.1, 37.1, 52.3 (2C),
59.2, 74.8, 84.6, 122.7 (2C), 127.1, 130.1 (2C), 151.2, 171.2
(2C), 210.2; HR-MS [(+)-ESI-TOF]: m/z=341.1372, calcd.
Pd-Catalyzed Cascade Cyclization
Spirocyclic adducts 2a–h, 4, 6, 8, 10, and 12, and tetrahydro-
naphthol derivative 14 were prepared according to the gen-
eral procedure.
+
for C18H22NaO5 (M+Na+): 341.1359.
Dimethyl
2-(buta-2,3-dien-1-yl)-2-(4-hydroxy-3,5-dime-
General Procedure
thoxybenzyl)malonate (5): White solid; mp 79–818C; IR
(ATR): n=3447, 2952, 1730, 1519, 1458, 1202, 1109, 1074,
A solution of 1 (52.2 mg, 0.18 mmol), PdACTHNURTGNENG(U dba)2 (5.2 mg,
844, 733 cmÀ1
;
1H NMR (CDCl3): d=2.58 (dt, J=8.0,
0.009 mmol), PPh3 (5.8 mg, 0.022 mmol), K2CO3 (99.5 mg,
0.72 mmol), and iodobenzene (30 mL, 0.27 mmol) in DMF
(18 mL) was heated at 908C for 3 h. The reaction mixture
was cooled down to room temperature and the solvent was
evaporated under reduced pressure. After dilution of the
residue with Et2O, the resulting solution was washed with
water and brine, dried over Na2SO4, and then concentrated
under vacuum. The crude residue was purified by flash
column chromatography (SiO2, hexane/AcOEt=3/1) to give
2.4 Hz, 2H), 3.20 (s, 2H), 3.73 (s, 3H), 3.84 (s, 3H), 4.76 (dt,
J=6.4, 2.4 Hz, 2H), 4.99 (tt, J=6.4, 8.0 Hz, 1H), 5.48 (s,
1H), 6.35 (s, 2H); 13C NMR (CDCl3): d=31.0, 37.8, 52.3
(2C), 56.1 (2C), 59.1, 74.9, 84.6, 106.6 (2C), 126.5, 133.6,
146.7 (2C), 170.9 (2C), 210.2; HR-MS [(+)-ESI-TOF]:
m/z=373.1243, calcd. for C18H22NaO7 (M+Na+): 373.1258.
+
Dimethyl
benzyl)malonate (7): White solid; mp 75–778C; IR (ATR):
n=3444, 2952, 1720, 1506, 1436, 1203, 1113, 1071, 850 cmÀ1
1H NMR (CDCl3): d=2.22 (s, 3H), 2.59 (dt, J=7.6, 2.4 Hz,
2-(buta-2,3-dien-1-yl)-2-(4-hydroxy-2-methyl-
;
dimethyl 8-oxo-4-(1-phenylvinyl)spiro
dicarboxylate 2a as colorless oil; yield: 58.4 mg (94%). IR
ACHTUNGTNER[NUNG 4.5]deca-6,9-diene-2,2-
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Palladium-Catalyzed Intramolecular ipso-Friedel–Crafts Allylic Alkylation of Phenols
(ATR): n=1729, 1662, 1252, 1200, 856, 733, 701 cmÀ1
;
10.4 Hz, 1H), 6.44 (dd, J=2.8, 10.4 Hz, 1H), 6.82 (dd, J=
2.8, 10.4 Hz, 1H), 6.96–6.99 (m, 2H), 7.19–7.21 (m, 2H);
13C NMR (CDCl3): d=31.3 (3C), 34.4, 37.6, 44.2, 50.6, 53.1,
53.2, 53.3, 57.5, 113.4, 124.9 (2C), 126.7 (2C), 127.5, 128.5,
138.8, 146.4, 149.3, 151.0, 153.3, 172.0, 172.5, 185.6; HR-MS
1H NMR (CDCl3): d=2.35 (d, J=14.8 Hz, 1H), 2.70 (d, J=
14.8 Hz, 1H), 2.76 (dd, J=6.4, 14.0 Hz, 1H), 2.90 (dd, J=
13.2, 14.0 Hz, 1H), 3.47 (dd, J=6.0, 13.2 Hz, 1H), 3.79 (s,
3H), 3.83 (s, 3H), 5.10 (s, 1H), 5.11 (s, 1H), 5.59 (dd, J=
2.0, 10.0 Hz, 1H), 6.14 (dd, J=2.0, 10.0 Hz, 1H), 6.44 (dd,
J=3.2, 10.0 Hz, 1H), 6.83 (dd, J=3.2, 10.0 Hz, 1H), 7.02–
7.05 (m, 2H), 7.17–7.20 (m, 3H); 13C NMR (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; HR-MS [(+)-ESI-TOF]: m/z=389.1385,
+
[(+)-ESI-TOF]: m/z=445.1984, calcd. for C26H30NaO5
(M+Na+): 445.1985.
Dimethyl
[4.5]deca-6,9-diene-2,2-dicarboxylate (2e): Pale yellow oil;
IR (ATR): n=1731, 1664, 1257, 1199, 1176, 1155, 860 cmÀ1
8-oxo-4-{1-[4-(tosyloxy)phenyl]vinyl}spiro-
AHCTUNGTRENNUNG
;
1H NMR (CDCl3): d=2.35 (d, J=14.8 Hz, 1H), 2.47 (s,
3H), 2.70 (d, J=14.8 Hz, 1H), 2.73 (dd, J=6.4, 13.6 Hz,
1H), 2.87 (dd, J=13.2, 13.6 Hz, 1H), 3.41 (dd, J=6.4,
13.2 Hz, 1H), 3.79 (s, 3H), 3.83 (s, 3H), 5.08 (s, 1H), 5.11 (s,
1H), 5.60 (dd, J=2.0, 10.0 Hz, 1H), 6.11 (dd, J=2.0,
10.0 Hz, 1H), 6.43 (dd, J=2.8, 10.0 Hz, 1H), 6.79 (dd, J=
2.8, 10.0 Hz, 1H), 6.80 (d, J=8.4 Hz, 1H), 6.97 (d, J=
8.4 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.70 (d, J=8.0 Hz,
1H); 13C NMR (CDCl3): d=21.7, 37.4, 44.2, 50.4, 52.7, 53.3,
53.4, 57.4, 114.8, 122.1 (2C), 128.0, 128.0 (2C), 128.5, 128.5
(2C), 129.9 (2C), 132.2, 140.7, 145.3, 145.4, 149.1, 149.2,
153.2, 171.9, 172.4, 185.2; HR-MS [(+)-ESI-TOF]: m/z=
559.1427, calcd. for C29H28NaO8S+ (M+Na+): 559.1397.
+
calcd. for C22H22NaO5 (M+Na+): 389.1359.
Cyclic dimer (2a’): Pale yellow oil; IR (ATR): n=1730,
1
1510, 1205, 1175, 1016, 737, 699 cmÀ1; H NMR (CDCl3): d=
2.74 (d, J=7.6 Hz, 4H), 3.30 (s, 4H), 3.81 (s, 12H), 4.51 (s,
4H), 5.74 (t, J=7.6 Hz, 2H), 6.65 (d, J=8.8 Hz, 4H), 6.95
(d, J=8.8 Hz, 4H), 7.27–7.36 (m, 6H), 7.42–7.45 (m, 4H);
13C NMR (CDCl3): d=30.7 (2C), 37.6 (2C), 52.8 (4C), 58.3
(2C), 65.3 (2C), 115.0 (4C), 126.4 (4C), 126.8 (2C), 127.4
(2C), 127.8 (2C), 128.3 (4C), 130.5 (4C), 138.5 (2C), 140.4
(2C), 157.9 (2C), 171.4 (4C); HR-MS [(+)-ESI-TOF]:
+
m/z=755.2821, calcd. for C44H44NaO10
(M+Na+):
755.2827.
Dimethyl
spiro[4.5]deca-6,9-diene-2,2-dicarboxylate (2b): Pale yellow
oil; IR (ATR): n=1722, 1712, 1662, 1252, 1174, 1101, 856,
715 cmÀ1 1H NMR (CDCl3): d=1.39 (t, J=7.2 Hz, 3H),
4-{1-[4-(ethoxycarbonyl)phenyl]vinyl}-8-oxo-
Dimethyl
spiro[4.5]deca-6,9-diene-2,2-dicarboxylate (2f): Pale yellow
oil; IR (ATR): n=1720, 1716, 1663, 1247, 857, 733 cmÀ1
4-{1-[3-(ethoxycarbonyl)phenyl]vinyl}-8-oxo-
G
ACHTUNGTRENNUNG
;
;
1H NMR (CDCl3): d=1.40 (t, J=7.2 Hz, 3H), 2.35 (d, J=
15.2 Hz, 1H), 2.73 (d, J=15.2 Hz, 1H), 2.78 (dd, J=6.0,
13.6 Hz, 1H), 2.91 (dd, J=13.2, 13.6 Hz, 1H), 3.50 (dd, J=
6.0, 13.2 Hz, 1H), 3.80 (s, 3H), 3.85 (s, 3H), 4.33–4.42 (m,
2H), 5.16 (s, 1H), 5.18 (d, J=1.2 Hz, 1H), 5.60 (dd, J=2.0,
10.0 Hz, 1H), 6.15 (dd, J=2.0, 10.0 Hz, 1H), 6.46 (dd, J=
3.2, 10.4 Hz, 1H), 6.85 (dd, J=3.2, 10.4 Hz, 1H), 7.19–7.26
(m, 2H), 7.76–7.77 (m, 1H), 7.87–7.90 (m, 1H); 13C NMR
(CDCl3): d=14.3, 37.4, 44.2, 50.5, 52.6, 53.3, 53.4, 57.5, 61.1,
115.0, 127.7, 127.8, 128.3, 128.6, 128.8, 130.1, 131.6, 141.9,
145.7, 149.3, 153.2, 166.3, 171.9, 172.3, 185.4; HR-MS
2.37 (d, J=14.4 Hz, 1H), 2.71 (d, J=14.4 Hz, 1H), 2.76 (dd,
J=6.4, 14.0 Hz, 1H), 2.90 (dd, J=13.2, 14.0 Hz, 1H), 3.49
(dd, J=6.4, 13.2 Hz, 1H), 3.80 (s, 3H), 3.84 (s, 3H), 4.35 (q,
J=7.2 Hz, 2H), 5.18 (s, 2H), 5.63 (dd, J=2.0, 10.0 Hz, 1H),
6.16 (dd, J=2.0, 10.0 Hz, 1H), 6.45 (dd, J=2.8, 10.4 Hz,
1H), 6.84 (dd, J=2.8, 10.4 Hz, 1H), 7.13 (dd, J=1.6, 6.4 Hz,
2H), 7.88 (dd, J=1.6, 6.4 Hz, 2H); 13C NMR (CDCl3): d=
14.3, 37.5, 44.2, 50.6, 52.6, 53.3, 53.4, 57.4, 61.0, 115.5, 126.8
(2C), 128.3, 128.6, 129.4 (2C), 129.7, 145.7, 146.3, 149.2,
153.1, 166.2, 171.9, 172.4, 185.4; HR-MS [(+)-ESI-TOF]:
+
+
m/z=461.1595, calcd. for C25H26NaO7 (M+Na+): 461.1571.
[(+)-ESI-TOF]: m/z=439.1780, calcd. for C25H27O7 (M+
Dimethyl
spiro[4.5]deca-6,9-diene-2,2-dicarboxylate (2c): Pale yellow
oil; IR (ATR): n=1731, 1663, 1323, 1254, 1162, 1110, 1064,
849 cmÀ1 1H NMR (CDCl3): d=2.39 (d, J=14.4 Hz, 1H),
8-oxo-4-{1-[4-(trifluoromethyl)phenyl]vinyl}-
H+): 439.1751.
G
Dimethyl 4-[1-(2-fluorophenyl)vinyl]-8-oxospiroACTHNGUETRNNU[G 4.5]deca-
6,9-diene-2,2-dicarboxylate (2g): Pale yellow oil; IR (ATR):
1
;
n=1730, 1663, 1257, 1202, 858, 764 cmÀ1; H NMR (CDCl3):
2.71 (d, J=14.4 Hz, 1H), 2.77 (dd, J=6.4, 14.0 Hz, 1H),
2.90 (dd, J=13.2, 14.0 Hz, 1H), 3.47 (dd, J=6.0, 13.2 Hz,
1H), 3.80 (s, 3H), 3.84 (s, 3H), 5.18 (s, 1H), 5.20 (d, J=
1.2 Hz, 1H), 5.65 (dd, J=2.0, 10.0 Hz, 1H), 6.17 (dd, J=1.6,
10.4 Hz, 1H), 6.44 (dd, J=3.2, 10.0 Hz, 1H), 6.84 (dd, J=
3.2, 10.4 Hz, 1H), 7.16–7.18 (m, 2H), 7.46–7.48 (m, 2H);
13C NMR (CDCl3): d=37.5, 44.2, 50.6, 52.7, 53.3, 53.4, 57.4,
115.9, 123.9 (q, J=270.8 Hz), 125.0 (q, J=3.9 Hz) (2C),
125.3, 127.2 (2C), 128.3, 128.7, 129.8 (q, J=32.5 Hz), 145.3,
145.4, 149.1, 153.0, 171.8, 172.4, 185.3; HR-MS [(+)-ESI-
d=2.30 (d, J=14.8 Hz, 1H), 2.74 (d, J=14.8 Hz, 1H), 2.79
(dd, J=6.4, 13.6 Hz, 1H), 2.91 (dd, J=13.2, 13.6 Hz, 1H),
3.56 (dd, J=6.4, 13.2 Hz, 1H), 3.79 (s, 3H), 3.83 (s, 3H),
5.13 (s, 1H), 5.26 (d, J=1.2 Hz, 1H), 5.65 (dd, J=2.0,
10.0 Hz, 1H), 6.16 (dd, J=2.0, 10.0 Hz, 1H), 6.53 (dd, J=
2.8, 10.0 Hz, 1H), 6.83–6.95 (m, 4H), 7.16–7.22 (m, 1H);
13C NMR (CDCl3): d=37.1, 44.3, 50.6, 52.0 (d, J=3.8 Hz),
53.2 53.3, 57.4, 115.1 (d, J=21.9 Hz), 116.8, 124.0 (d, J=
2.8 Hz), 128.1, 128.7, 129.0 (d, J=14.3 Hz), 129.5 (d, J=
8.6 Hz), 130.5 (d, J=3.8 Hz), 142.4, 149.2, 153.0, 159.0 (d,
+
TOF]: m/z=435.1387, calcd. for C23H22F3O5 (M+H+):
J=245.0 Hz), 172.0, 172.3, 185.6; HR-MS [(+)-ESI-TOF]:
+
435.1414.
m/z=407.1240, calcd. for C22H21FNaO5
(M+Na+):
Dimethyl
4-{1-[4-(tert-butyl)phenyl]vinyl}-8-oxospiro-
407.1265.
A
Dimethyl
4-[1-(naphthalen-2-yl)vinyl]-8-oxospiro-
IR (ATR): n=2954, 1731, 1663, 1252, 1200, 1095, 857 cmÀ1
;
ACHTUNGERTN[NUNG 4.5]deca-6,9-diene-2,2-dicarboxylate (2h): Pale yellow oil;
1H NMR (CDCl3): d=1.28 (s, 9H), 2.34 (d, J=14.8 Hz,
1H), 2.70 (d, J=14.8 Hz, 1H), 2.75 (dd, J=6.0, 14.0 Hz,
1H), 2.88 (dd, J=13.2 Hz, 14.0 Hz, 1H), 3.46 (dd, J=6.0,
13.2 Hz, 1H), 3.79 (s, 3H), 3.83 (s, 3H), 5.06 (s, 1H), 5.11 (s,
1H), 5.57 (dd, J=2.0, 10.4 Hz, 1H), 6.13 (dd, J=2.0,
IR (ATR): n=1729, 1662, 1253, 1200, 856, 734 cmÀ1
;
1H NMR (CDCl3): d=2.38 (d, J=14.8 Hz, 1H), 2.72 (d, J=
14.8 Hz, 1H), 2.82 (dd, J=6.0, 14.0 Hz, 1H), 2.95 (dd, J=
13.2, 14.0 Hz, 1H), 3.61 (dd, J=6.0, 13.2 Hz, 1H), 3.80 (s,
3H), 3.85 (s, 3H), 5.20 (s, 1H), 5.23 (s, 1H), 5.46 (dd, J=
Adv. Synth. Catal. 2013, 355, 2693 – 2700
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2697

Tetsuhiro Nemoto et al.
UPDATES
2.0, 10.0 Hz, 1H), 6.18 (dd, J=2.0, 10.4 Hz, 1H), 6.44 (dd,
J=3.2, 10.0 Hz, 1H), 6.89 (dd, J=3.2, 10.4 Hz, 1H), 7.18
(dd, J=1.6, 8.8 Hz, 1H), 7.43–7.51 (m, 3H), 7.73–7.78 (m,
3H); 13C NMR (CDCl3): d=37.6, 44.3, 50.8, 53.2, 53.3, 53.4,
57.5, 114.7, 125.4, 125.5, 126.0, 126.3, 127.6, 127.8, 127.9,
128.0, 128.6, 132.7, 132.8, 139.2, 146.4, 149.4, 153.2, 172.0,
172.5, 185.5; HR-MS [(+)-ESI-TOF]: m/z=439.1535, calcd.
4-(1-Phenylvinyl)-2-tosyl-2-azaspiroACTHNGUTERNN[UG 4.5]deca-6,9-dien-8-
one (12): Yellow oil; IR (ATR): n=1664, 1344, 1162, 1091,
1
858, 703, 662 cmÀ1; H NMR (CDCl3): d=2.49 (s, 3H), 3.40
(d, J=10.4 Hz, 1H), 3.44 (d, J=10.4 Hz, 1H), 3.50 (dd, J=
8.0, 10.0 Hz, 1H), 3.71 (dd, J=10.0, 10.4 Hz, 1H), 3.90 (dd,
J=8.0, 10.4 Hz, 1H), 4.99 (s, 1H), 5.18 (s, 1H), 5.72 (dd, J=
2.0, 10.0 Hz, 1H), 6.09 (dd, J=2.0, 10.4 Hz, 1H), 6.28 (dd,
J=3.2, 10.0 Hz, 1H), 6.41 (dd, J=3.2, 10.4 Hz, 1H), 6.97–
7.00 (m, 2H), 7.16–7.22 (m, 3H), 7.41 (d, J=8.0 Hz, 2H),
7.78 (d, J=8.0 Hz, 2H); 13C NMR (CDCl3): d=21.6, 49.8,
50.0, 51.7, 56.4, 115.1, 126.7 (2C), 127.5 (2C), 128.1, 129.6
(2C), 129.8, 130.0, 133.4 (2C), 141.1, 144.2, 144.3, 146.5,
148.8, 185.0; HR-MS [(+)-ESI-TOF]: m/z=406.1494, calcd.
for C24H24NO3S+ (M+H+): 406.1471.
+
for C26H24NaO5 (M+Na+): 439.1516.
Dimethyl
7,9-dimethyl-8-oxo-4-(1-phenylvinyl)spiro-
[4.5]deca-6,9-diene-2,2-dicarboxylate (4): Yellow oil; IR
(CDCl3): d=1.34 (s, 3H), 1.83 (s, 3H), 2.30 (d, J=14.4 Hz,
1H), 2.66 (d, J=14.4 Hz, 1H), 2.71 (dd, J=6.0, 14.0 Hz,
1H), 2.86 (dd, J=13.2, 14.0 Hz, 1H), 3.40 (dd, J=6.0,
13.2 Hz, 1H), 3.79 (s, 3H), 3.83 (s, 3H), 5.04 (s, 2H), 6.20
(d, J=1.2 Hz, 1H), 6.54 (d, J=1.2 Hz, 1H), 6.95–6.98 (m,
2H), 7.14–7.20 (m, 3H); 13C NMR (CDCl3): d=15.4, 16.2,
37.4, 43.9, 49.7, 52.3, 53.1, 53.2, 57.6, 113.6, 126.9 (2C),
127.5, 127.9 (2C), 134.1, 134.3, 141.8, 144.5, 147.3, 149.3,
172.2, 172.7, 186.6; HR-MS [(+)-ESI-TOF]: m/z=417.1673,
Dimethyl 7-hydroxy-8-methyl-4-(1-phenylvinyl)-3,4-dihy-
dronaphthalene-2,2(1H)-dicarboxylate (14): Yellow oil; IR
(ATR): n=3475, 1734, 1490, 1436, 1251, 1073, 703 cmÀ1
;
1H NMR (CDCl3): d=2.08 (dd, J=10.8, 13.2 Hz, 1H), 2.21
(s, 3H), 2.57 (dd, J=6.0, 13.2 Hz, 1H), 3.01 (d, J=16.8 Hz,
1H), 3.39 (d, J=16.8 Hz, 1H), 3.69 (s, 3H), 3.71 (s, 3H),
4.05 (dd, J=6.0, 10.8 Hz, 1H), 4.57 (s, 1H), 5.05 (s, 1H),
5.44 (s, 1H), 6.60 (d, J=8.4 Hz, 1H), 7.01 (d, J=8.4 Hz,
1H), 7.21–7.26 (m, 5H); 13C NMR (CDCl3): d=11.3, 32.5,
34.0, 42.9, 52.8, 52.8, 53.8, 113.5, 116.3, 121.4, 126.8 (2C),
127.0, 127.4, 128.2 (2C), 129.0, 133.8, 140.9, 151.7, 151.7,
171.5, 172.2; HR-MS [(+)-ESI-TOF]: m/z=381.1679, calcd.
+
calcd. for C24H26NaO5 (M+Na+): 417.1672.
Dimethyl
[4.5]deca-6,9-diene-2,2-dicarboxylate (6): Yellow oil; IR
(ATR): n=1728, 1667, 1618, 1250, 1199, 1108, 777, 731,
700 cmÀ1 1H NMR (CDCl3): d=2.33 (d, J=14.4 Hz, 1H),
7,9-dimethoxy-8-oxo-4-(1-phenylvinyl)spiro-
ACHTUNGTRENNUNG
;
2.74 (dd, J=6.4, 14.0 Hz, 1H), 2.80 (d, J=14.4 Hz, 1H),
2.99 (dd, J=13.2, 14.0 Hz, 1H), 3.18 (s, 3H), 3.48 (dd, J=
6.4, 13.2 Hz, 1H), 3.61 (s, 3H), 3.80 (s, 3H), 3.84 (s, 3H),
5.08 (s, 1H), 5.09 (s, 1H), 5.31 (d, J=2.4 Hz, 1H), 5.79 (d,
J=2.4 Hz, 1H), 6.99–7.02 (m, 2H), 7.16–7.28 (m, 3H);
13C NMR (CDCl3): d=37.2, 46.0, 49.2, 53.2, 53.3, 54.1, 54.6,
55.1, 57.1, 114.1, 116.2, 121.3, 126.8 (2C), 127.5, 128.1 (2C),
142.3, 146.9, 149.9, 150.4, 172.5, 172.7, 176.0; HR-MS
+
for C23H25O5 (M+H+): 381.1697.
Dimethyl 6-Hydroxy-8-methyl-4-(1-phenylvinyl)-3,4-
dihydronaphthalene-2,2(1H)-dicarboxylate (15)
To a solution of 8 (30.6 mg, 0.08 mmol) in CH3CN (4 mL) at
room temperature was added TsOH·H2O (7.6 mg,
0.04 mmol) and the mixture was stirred at 408C for 12 h.
The reaction was quenched with saturated aqueous
NaHCO3 and the aqueous layer was extracted with AcOEt.
The combined organic layers were washed with brine, dried
over Na2SO4, and then concentrated under vacuum. The ob-
tained residue was purified by flash column chromatography
(SiO2, hexane/acetone=3:1) to give 15 as a colorless oil;
yield: 26.3 mg (86%). IR (ATR): n=3445, 1732, 1435, 1238,
+
[(+)-ESI-TOF]: m/z=449.1588, calcd. for C24H26NaO7
(M+Na+): 449.1571.
Dimethyl 6-methyl-8-oxo-4-(1-phenylvinyl)spiro
6,9-diene-2,2-dicarboxylate (8): Pale yellow oil; IR (ATR):
n=1734, 1665, 1457, 1364, 1204 cmÀ1 1H NMR (major
ACHTUNGTRENUN[NG 4.5]deca-
;
isomer, CDCl3): d=1.79 (s, 3H), 2.35 (d, J=14.8 Hz, 1H),
2.74 (dd, J=6.4, 14.0 Hz, 1H), 2.80 (d, J=14.8 Hz, 1H),
2.85 (dd, J=13.2, 14.0 Hz, 1H), 3.63 (dd, J=6.4, 13.2 Hz,
1H), 3.80 (s, 3H), 3.84 (s, 3H), 5.08 (s, 2H), 5.64 (d, J=
2.0 Hz, 1H), 6.16 (dd, J=2.0, 10.4 Hz, 1H), 6.89 (d, J=
10.4 Hz, 1H), 7.00–7.06 (m, 2H), 7.13–7.24 (m, 3H);
13C NMR (major isomer, CDCl3): d=19.1, 37.7, 43.1, 50.4,
52.9, 53.3, 53.3, 57.5, 114.6, 126.8 (2C), 127.2, 127.7, 127.9
(2C), 129.6, 141.7, 146.5, 151.1, 159.2, 172.0, 172.6, 185.6;
HR-MS [(+)-ESI-TOF]: m/z=403.1538, calcd. for
1080, 1030, 735, 701 cmÀ1 1H NMR (CDCl3): d=2.09 (dd,
;
J=11.2, 13.6 Hz, 1H), 2.26 (s, 3H), 2.58 (dd, J=2.0, 6.0 Hz,
13.6 Hz, 1H), 2.92 (d, J=16.0 Hz, 1H), 3.31 (dd, J=2.0,
16.0 Hz, 1H), 3.67 (s, 3H), 3.69 (s, 3H), 4.05 (dd, J=6.0,
11.2 Hz, 1H), 4.84 (s, 1H), 5.06 (s, 1H), 5.45 (d, J=0.8 Hz,
1H), 6.55 (d, J=2.4 Hz, 1H), 6.61 (d, J=2.4 Hz, 1H), 7.20–
7.25 (m, 5H); 13C NMR (CDCl3): d=19.9, 31.4, 34.1, 43.5,
52.7, 52.8, 53.8, 112.6, 115.6, 116.6, 124.5, 126.7 (2C), 127.5,
128.3 (2C), 137.8, 138.1, 140.7, 151.3, 153.5, 171.5, 172.2;
HR-MS [(+)-ESI-TOF]: m/z=381.1673, calcd. for
+
C23H24NaO5 (M+Na+): 403.1516.
Dimethyl
tane-1,1’-naphthalene]-4,4-dicarboxylate (10): Yellow oil; IR
(ATR): n=1728, 1662, 1255, 1203, 767, 734, 699 cmÀ1
4’-oxo-2-(1-phenylvinyl)-4’H-spiro[cyclopen-
+
C23H25O5 (M+H+): 381.1697.
;
1H NMR (major isomer, CDCl3): d=2.80 (d, J=15.2 Hz,
1H), 2.84 (dd, J=6.0, 13.6 Hz, 1H), 3.07 (dd, J=1.2,
15.2 Hz, 1H), 3.08 (dd, J=13.2, 13.2 Hz, 1H), 3.70 (ddd, J=
1.2, 6.0, 15.2 Hz, 1H), 3.83 (s, 3H), 3.91 (s, 3H), 4.83 (s,
1H), 4.91 (s, 1H), 5.84 (d, J=10.0 Hz, 1H), 6.50–6.52 (m,
2H), 6.86–7.01 (m, 4H), 7.33–7.64 (m, 3H), 7.93 (dd, J=1.2,
8.0 Hz, 1H); 13C NMR (major isomer, CDCl3): d=39.6,
48.1, 50.1, 53.1, 53.2, 53.3, 59.1, 115.0, 126–146 (9C), 146.9,
155.4, 171.6, 172.6, 183.9; HR-MS [(+)-ESI-TOF]: m/z=
Dimethyl 8-Methyl-4-(1-phenylvinyl)-3,4-dihydro-
naphthalene-2,2(1H)-dicarboxylate (16)
To a stirred solution of 8 (32.4 mg, 0.085 mmol) in MeOH
(1.7 mL) at room temperature was added CeCl3·7H2O
(31.7 mg, 0.085 mmol), and the resulting suspension was
stirred for 10 min. NaBH4 (6.4 mg, 0.17 mmol) was added to
the mixture and the reaction was stirred for 1 h at 08C, and
then quenched with water. After a half of solvent had been
+
439.1675, calcd. for C26H25O5 (M+H+): 417.1697.
2698
asc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 2693 – 2700

Palladium-Catalyzed Intramolecular ipso-Friedel–Crafts Allylic Alkylation of Phenols
evaporated under vacuum, the mixture was diluted with
AcOEt, washed with brine, and then dried over Na2SO4.
After concentration under vacuum, the obtained residue
was directly utilized for the next reaction.
[3] Other representative examples of the synthesis of spi-
rocyclohexadienones, see: halocyclization; a) T. R.
Appel, N. A. M. Yehia, U. Baumeister, H. Hartung, R.
Kluge, D. Strçhl, E. Fanghꢄnel, Eur. J. Org. Chem.
2003, 47; b) X. Zhang, R. C. Larock, J. Am. Chem. Soc.
2005, 127, 12230; c) B.-X. Tang, D.-J. Tang, S. Tang, Q.-
F. Yu, Y.-H. Zhang, Y. Liang, P. Zhong, J.-H. Li, Org.
Lett. 2008, 10, 1063; d) B.-X. Tang, R.-Y. Tang, J.-H. Li,
J. Org. Chem. 2008, 73, 9008; e) Q. Yin, S.-L. You, Org.
Lett. 2012, 14, 3526; radical cyclization; f) F. Gonzꢅlez-
Lꢃpez de Turiso, D. P. Curran, Org. Lett. 2005, 7, 151;
g) T. Lanza, R. Leardini, M. Minozzi, D. Nanni, P.
Spagnolo, G. Zanardi, Angew. Chem. 2008, 120, 9581;
Angew. Chem. Int. Ed. 2008, 47, 9439; hypervalent
iodine reagents: h) T. Dohi, A. Maruyama, M. Yoshi-
mura, K. Morimoto, H. Tohma, Y. Kita, Angew. Chem.
2005, 117, 6349; Angew. Chem. Int. Ed. 2005, 44, 6193;
i) T. Dohi, A. Maruyama, Y. Minamitsuji, N. Takenaga,
Y. Kita, Chem. Commun. 2007, 1224; j) Y. Dohi, Y.
Minamitsuji, A. Maruyama, S. Hirose, Y. Kita, Org.
Lett. 2008, 10, 3559; arylative dearomatization; k) S.
Rousseaux, J. Garcꢂa-Fortanet, M. A. Del Aguila San-
chez, S. L. Buchwald, J. Am. Chem. Soc. 2011, 133,
9282. Other metal-mediated methods; l) F. C. Pigge,
J. J. Coniglio, N. P. Rath, Org. Lett. 2003, 5, 2011;
m) F. C. Pigge, J. J. Coniglio, R. Dalvi, J. Am. Chem.
Soc. 2006, 128, 3498; n) F. C. Pigge, R. Dhanya, E. R.
Hoefgen, Angew. Chem. 2007, 119, 2945; Angew.
Chem. Int. Ed. 2007, 46, 2887; o) S. Chiba, L. Zhang, J.-
Y. Lee, J. Am. Chem. Soc. 2010, 132, 7266.
To a stirred solution of the crude product in CH3CN
(1.7 mL) at room temperature was added TsOH·H2O
(16.2 mg, 0.085 mmol). After 30 min, the reaction mixture
was quenched with saturated aqueous NaHCO3. The aque-
ous layer was extracted with AcOEt, and the combined or-
ganic layers were washed with brine. After concentration
under vacuum, the obtained residue was purified by flash
column chromatography (SiO2, hexane/acetone=8:1) to
give 16 as a colorless oil; yield: 21.7 mg (71%). IR (ATR):
n=2952, 1733, 1434, 1243, 1197, 1175, 779, 703 cmÀ1
;
1H NMR (CDCl3): d=2.14 (dd, J=10.8, 13.6 Hz, 1H), 2.33
(s, 3H), 2.61 (ddd, J=1.6, 6.0, 13.6 Hz, 1H), 3.04 (d, J=
16.4 Hz, 1H), 3.36 (dd, J=1.6, 16.4 Hz, 1H), 3.68 (s, 3H),
3.71 (s, 3H), 4.13 (dd, J=6.0, 10.8 Hz, 1H), 5.04 (s, 1H),
5.46 (d, J=0.8 Hz, 1H), 7.03–7.16 (m, 3H); 13C NMR
(CDCl3): d=19.9, 32.0, 34.1, 43.2, 52.7, 52.7, 53.7, 116.4,
125.9, 126.6, 126.7 (2C), 127.5, 128.0, 128.3 (2C), 132.4,
136.1, 136.7, 140.9, 151.6, 171.4, 172.1; HR-MS [(+)-ESI-
+
TOF]: m/z=387.1575, calcd. for C23H24NaO4 (M+Na+):
387.1567.
Acknowledgements
This work was supported by a Grant-in Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Sci-
ence, and Technology, Japan, the Research Foundation for
Pharmaceutical Sciences, and the Uehara Memorial Founda-
tion.
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UPDATES
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