Chiral Hypervalent Organoiodine-Catalyzed Enantioselective Oxidative Spirolactonization of Naphthol Derivatives

Article abstract of DOI:10.1021/acs.joc.7b01941

Highly enantioselective oxidative dearomatization of 2-naphthol derivatives was achieved for the first time by using conformationally flexible organoiodine catalysts derived from 2-aminoalcohol as a chiral source. Moreover, with the use of these catalysts

Full text of DOI:10.1021/acs.joc.7b01941

Note
pubs.acs.org/joc
Chiral Hypervalent Organoiodine-Catalyzed Enantioselective
Oxidative Spirolactonization of Naphthol Derivatives
Muhammet Uyanik, Takeshi Yasui, and Kazuaki Ishihara*
Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603, Japan
S
* Supporting Information
ABSTRACT: Highly enantioselective oxidative dearomatization of 2-naphthol derivatives was achieved for the first time by
using conformationally flexible organoiodine catalysts derived from 2-aminoalcohol as a chiral source. Moreover, with the use of
these catalysts, excellent enantioselectivities were also achieved for 1-naphthol derivatives, which had previously been obtained
with only lower enantioselectivities. Furthermore, the product obtained from the present reaction could be transformed to a
highly functionalized spirolactone in high yield and with excellent stereoselectivity.
Scheme 1. Conformationally Flexible Chiral
Organoiodine(III) Catalysts
he enantioselective oxidative dearomatization of arenols
and their analogues is a useful method for the synthesis of
T
several important medicinally and biologically active com-
pounds.1 On the other hand, the development of asymmetric
redox catalysis based on hypervalent iodine chemistry is
currently one of the most progressive research areas in
asymmetric organocatalysis.2,3 Kita and colleagues succeeded
in the first enantioselective oxidative dearomatization of 1-
naphthol derivatives with chiral a μ-oxo-bridged-hypervalent
iodine(III), which has a conformationally rigid 1,1-spiroinda-
none backbone.4 In contrast to Kita’s conformationally rigid
catalysts, we demonstrated the rational design of conforma-
tionally flexible hypervalent organoiodines(III) as chiral
catalysts based on secondary nonbonding interactions (i.e.,
intramolecular hydrogen-bonding interactions between the
acidic amido protons and the iodine(III) ligands) for the
same reaction (Scheme 1).5,6
In 2010, we designed C2-symmetric organoiodine 1 (1st-
generation precatalyst) derived from lactate as a chiral source
for the catalytic enantioselective oxidative spirolactonization of
1-naphthol derivatives 3 to the corresponding spirolactones 4
(Scheme 2, eq 1).5a,b However, 1 was found to be insufficient
for the oxidation of phenols 5, which were less reactive than 1-
naphthols, with respect to not only reactivity but also
enantioselectivity.6a To overcome these limitations, we
designed new chiral organoiodines 2 derived from 2-amino-
alcohol instead of lactate as a chiral source (Scheme 1), and the
desired cyclohexadienone spirolactones 6 could be obtained
with excellent enantioselectivities (up to 99% ee, Scheme 2, eq
2).6a Moreover, we succeeded in rationally controlling the
desired associated pathway1h,7 using alcohol additives such as
methanol or ethanol (for electron-rich phenols) and 1,1,1,3,3,3-
hexafluoroisopropanol (HFIP) (for electron-deficient phe-
nols).6 X-ray diffraction and NOE (Nuclear Overhauser
Effect)−NMR analyses of in situ-generated organoiodines(III)
showed that a suitable chiral environment around the
Special Issue: Hypervalent Iodine Reagents
Received: August 1, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.7b01941
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Scheme 2. Enantioselective Oxidative Dearomatization of
Arenols
Table 1. Enantioselective Oxidative Dearomatization of 2-
Naphthol 7a
a
precat
(mol %)
additive
(equiv)
T (°C), t
(h)
8a, yield
(%)
8a, ee
b
entry
(%)
1
2
3
4
5
6
7
8
9
1 (10)
2a (10)
2b (10)
2b (10)
2b (5)
2b (10)
2b (5)
2a (5)
−
−
−
−
−
0, 30
36
84
71
72
63
72
87
89
50
36
77
86
89
89
76
95
94
79
0, 4
0, 6
−20, 18
−20, 24
−20, 24
−20, 15
−20, 15
−20, 15
c
EtOH (6)
d
HFIP (50)
HFIP (50)
HFIP (50)
d
d
1 (10)
a
Reactions were performed using purified m-CPBA (>99% purity).
Determined by HPLC analysis. 8a was obtained in 20% yield with
b
c
73% ee in the presence of 2a as a precatalyst and MeOH (25 equiv)6a
as an additive under identical conditions. Dichloromethane was used
d
as a solvent instead of DCE.
reactivity and enantioselectivity for the oxidation of 2-
naphthols, and 8a was obtained in 87% yield with 95% ee
after a shorter reaction time (entry 7).12 Interestingly, the use
of precatalyst 2a gave the same high reactivity and
enantioselectivity (89% yield, 94% ee) in the presence of
HFIP (entry 8). The beneficial effect of HFIP for the present
oxidation was also confirmed with the use of lactate-based
precatalyst 1 (entry 9 versus entry 1). Although the additional
effects of alcohols are not yet clear, the beneficial effect of HFIP
for the oxidation of 2-naphthols, which are less reactive than 1-
naphthols, is similar to our previous results regarding the
oxidation of phenols, where HFIP was used for the oxidation of
less-reactive phenols.6a
To explore the generality and substrate scope of the present
oxidative spirolactonization, several 2-naphthol derivatives 7
were examined as substrates in the presence of 5 mol % of 2a as
a precatalyst and HFIP as an additive under optimized
conditions in dichloromethane (Table 2).11 The corresponding
spirolactones 8b−i were obtained in moderate to high yields
and with high enantioselectivities (87−95% ee). As an
exception, the use of 2b instead of 2a as a precatalyst for the
oxidation of 7e gave slightly higher enantioselectivity (entry 4).
The oxidation of alkoxy group-substituted 7f and 7h gave
relatively lower chemical yields as well as enantioselectivities,
due to formation of several unidentified side-products (entries
5 and 7). Importantly, enantiomerically almost pure (99% ee)
8b was obtained after a single recrystallization (entry 1). The
absolute configurations of 8 were determined to be (S) on the
basis of the X-ray diffraction analysis of 8b.11,14
iodine(III) center was constructed via intramolecular hydrogen-
bonding interactions (Scheme 1).6a
Further studies revealed that our first-generation precatalyst
1 was less effective for the oxidation of not only phenols 5 but
also 2-naphthol derivatives 7, which were both less reactive
than 3 (Scheme 2, eq 3). On the other hand, arylative8 or
oxidative9 methods for the enantioselective dearomatization of
2-naphthol derivatives have recently been reported with the use
of transition metal or organocatalysts. Here, we report the first
transition metal-free enantioselective oxidative dearomatization
of 2-naphthols.10 We achieved a highly enantioselective
oxidative dearomatization of 2-naphthol derivatives 7 by using
our second-generation precatalysts 2 in the presence of HFIP as
an additive (Scheme 2, eq 4). Moreover, we also achieved
excellent enantioselectivities (up to 98% ee) for the oxidative
dearomatization of 1-naphthol derivatives 3 by using 2 in the
presence of ethanol as an additive (Scheme 2, eq 4).
Initially, iodoarenes 2 were examined as precatalysts for the
enantioselective oxidative cyclization of 2-naphthol derivative
7a in the presence of m-CPBA as an oxidant in 1,2-
dichloroethane (DCE) (Table 1).11 As in our previous studies
on the oxidation of phenols,6a bis(mesityl carboxamide) 2a was
superior to first-generation precatalyst 1 with respect to both
reactivity and enantioselectivity (entry 2 versus entry 1). The
oxidation of 7a in the presence of 10 mol % of 2a gave 8a in 84
yield with 77% ee (entry 2). Furthermore, bis(9-anthracenyl
carboxamide) 2b, a new precatalyst, was superior to 2a (entry
3), and the enantioselectivity was increased to 89% ee at −20
°C (entry 4). Notably, the catalyst loading of 2b could be
reduced to 5 mol % without affecting the enantioselectivity,
although the chemical yield was slightly decreased (entry 5).
Next, additional effects of alcohols6a on the reactivity and
enantioselectivity were examined for the present oxidation. The
enantioselectivity of 9a significantly decreased in the presence
of ethanol or methanol as an additive (entry 6). On the other
hand, in sharp contrast to the results with 1-naphthols,5a,11 the
additional use of HFIP in dichloromethane improved both the
Next, the enantioselective oxidative spirolactonization of 1-
naphthol derivatives 3 was examined using 5 mol % of 2a as a
precatalyst in DCE (Table 3).11 In contrast to the results with
2-naphthols (Table 1), the use of ethanol as an additive for the
oxidation of 1-naphthols 3 provided higher enantioselectivity.13
As a result, the oxidative dearomatization of known 1-naphthol
derivatives 3b−g5 and a new substrate 3h gave the
corresponding spirolactones (S)-4b−h in high yields and with
high to excellent enantioselectivities (91−98%). Notably, these
B
DOI: 10.1021/acs.joc.7b01941
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The Journal of Organic Chemistry
Note
recrystallization. The relative stereochemistry of 9 was
determined by X-ray diffraction analysis.11,14
Table 2. Enantioselective Oxidative Dearomatization of 2-
Naphthols 7
a
In summary, we achieved an enantioselective oxidative
dearomatization of 2-naphthol derivatives for the first time by
using our conformationally flexible organoiodine catalysts.
Moreover, excellent enantioselectivities were achieved for 1-
naphthol derivatives, which had previously been obtained with
lower enantioselectivities. Interestingly, the use of HFIP and
methanol as additives6 was crucial to induce high enantiose-
lectivity for 2-naphthol and 1-napthols, respectively. Further-
more, a highly functionalized spirolactone can be synthesized
from the oxidation of 2-naphthol derivative in high yield and
with excellent stereoselectivity.
b
entry
R
7
8, yield (%)
8, ee (%)
c
1
2
3
3-Br
6-Br
8-F
7b
7c
7d
7e
7f
85
95
92
83
51
85
57
99
89 (99)
95
95
95
89
91
87
95
d
4
4-Me
5
6
7
8
7-OMe
7-OMOM
7-OBn
6-CN
EXPERIMENTAL SECTION
7g
7h
7i
■
General Information. Infrared (IR) spectra were recorded on a
JASCO FT/IR 460 plus spectrometer. 1H NMR spectra were
measured on a JEOL ECS-400 (400 MHz) spectrometer at ambient
temperature. Data were recorded as follows: chemical shift in ppm
from internal tetramethylsilane on the δ scale, multiplicity (s = singlet;
d = doublet; t = triplet; q = quartet; m = multiplet, brs = broad
singlet), coupling constant (Hz), integration, and assignment. 13C
NMR spectra were measured on a JEOL ECS-400 (100 MHz)
spectrometers. Chemical shifts were recorded in ppm from the solvent
resonance employed as the internal standard (deuterochloroform at
77.00 ppm). 19F NMR spectra were measured on a JEOL ECS-400
(376 MHz) spectrometer. For thin-layer chromatography (TLC)
analysis throughout this work, Merck precoated TLC plates (silica gel
60 GF254 0.25 mm) were used. Visualization was accomplished by UV
light (254 nm), cerium ammonium molybdate and phosphomolybdic
acid. The products were purified by column chromatography on silica
gel (E. Merck Art. 9385, Kanto Chemical Co., Inc. 37560 or Fuji
Silysia Chemical, Cromatorex NH-DM1020). High-resolution mass
spectral analyses (HRMS) were performed at Chemical Instrument
Center, Nagoya University (JEOL JMS-700). The mass analyzer type
used for HRMS measurements is magnetic sector. High-performance
liquid chromatography (HPLC) analysis was conducted using
Shimadzu LC-10 AD coupled diode array-detector SPD-MA-10A-VP
and chiral column of Daicel CHIRALCEL OD-H (4.6 mm × 25 cm),
OD-3 (4.6 mm × 25 cm), IA-3 (4.6 mm × 25 cm), IC-3 (4.6 mm × 25
cm), AS-3 (4.6 mm × 25 cm).
a
b
d
Reactions were performed using purified m-CPBA (>99% purity).
Determined by HPLC analysis. After a single recrystallization.
Precatalyst 2b was used instead of 2a. 8e was obtained in 65% yield
c
with 89% ee using 2a under identical conditions.
Table 3. Enantioselective Oxidative Dearomatization of 1-
a
Naphthols 3
b
entry
1
R
3
time (h) 4, yield (%) 4, ee (%)
H
3a
2b
3c
3d
3e
3f
36
23
24
43
23
60
23
36
86
93
99
90
99
74
73
56
98
98
95
96
96
97
97
91
c
2
4-Cl
4-Br
4-Ph
3
4
5
6
d
4-CO(p-BrC6H4)
3-CH2OBn
6-OMe
c
7
3g
3h
8
5-NHTs
a
Reactions were performed using purified m-CPBA (>99% purity).
In experiments that required dry solvents, toluene, tetrahydrofuran
(THF), dichloromethane and dichloroethane, were purchased from
Wako Pure Chemical Industries Ltd. or Kanto Chemical Co., Inc. as
the “anhydrous” and stored over 4 Å molecular sieves. Chloroform was
purchased from Nacalai Tesque, Inc. (Lot No.; V2H8527, Code;
08402−55). Other solvents were purchased from Aldrich, Wako or
Kanto and used without further purification. Precatalyst 15 and 2a,6a
substrates 3a−g5 and products 4a−g5 are known compounds.
Precatalyst 1 can be purchased from Wako Pure Chemical Industries,
Ltd. or Tokyo Chemical Industry Co., Ltd. Other simple chemicals
were analytical-grade and obtained commercially and used without
further purification.
Commercially available m-CPBA (Aldrich, ca. 77% purity) was
purified by standard methods16 to give pure m-CPBA (≥99% purity).
Although the commercial m-CPBA could be also used, purified m-
CPBA gave more reproducible results. Phosphate buffer (pH 7.8 at
23.7 °C) was prepared from NaH2PO4·2H2O (2.40 g) and Na2HPO4
(23.4 g) in distilled H2O (900 mL), and used for purification of m-
CPBA.
b
c
d
Determined by HPLC analysis. 2a (10 mol %). At 0 °C.
spirolactones 4b−g were obtained in lower chemical yield (40−
94% yield) with lower enantioselectivities (83−92% ee) with
the use of our first-generation precatalyst 1.5
With a versatile and enantioselective synthesis of spirolac-
tones in hand, we sought to demonstrate the further synthetic
utility of these compounds (Scheme 3). The stereoselective
reduction of 8a under Luche conditions15 gave a single
diastereomer of allylic alcohol in 96% yield, which was
diastereoselectively transformed to bromohydrin (+)-9 in
94% yield (≥95:5 dr) using NBS. Fortunately, enantiomerically
pure (+)-9 (>99% ee) was obtained after a single
Scheme 3. Transformation of 8a to 9
N,N′-(2S,2′S)-2,2′-(2-Iodo-1,3-phenylene)bis(oxy)bis(propane-
2,1-diyl)dianthracene-9-carboxamide (2b). This compound was
prepared as 2a from (2S,2′S)-2,2′-(2-iodo-1,3-phenylene)bis(oxy)-
dipropan-1-amine6a with 9-anthracenecarbonyl chloride in 73% yield
(0.544 g, 0.730 mmol).6a Pale yellow solid; TLC, Rf = 0.50 (hexane−
1
EtOAc = 1:1); IR (KBr) 3395, 3300−3200, 1649 cm−1; H NMR
(CDCl3, 400 MHz) δ 1.48 (d, J = 6.0 Hz, 6H), 3.65−3.72 (m, 2H),
4.19 (ddd, J = 3.2, 6.8, 13.6 Hz, 2H), 4.84−4.88 (m, 2H), 6.61−6.66
C
DOI: 10.1021/acs.joc.7b01941
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The Journal of Organic Chemistry
Note
(m, 4H), 7.32 (t, J = 8.4 Hz, 1H), 7.10−8.20 (m, 16H), 8.44 (s, 2H);
13C{1H} NMR (CDCl3, 100 MHz) δ 17.7, 45.0, 75.0, 82.4, 107.2,
124.9, 125.3, 126.5, 127.9, 128.3, 128.4, 130.0, 130.9, 131.4, 157.7,
169.7; HRMS (FAB) m/z calcd for [C42H35IN2O4 + H]+ 759.1714,
(d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 9.87 (brs, 1H), 12.12
(brs, 1H); 13C{1H} NMR (DMSO-d6, 100 MHz) δ 22.4 (d, JC−F = 11
Hz), 34.8, 111.6 (d, JC−F = 24 Hz), 116.1 (d, JC−F = 5 Hz), 119.0,
122.2 (d, JC−F = 9 Hz), 123.1 (d, JC−F = 11 Hz), 125.0 (d, JC−F = 3
Hz), 127.8, 130.8 (d, JC−F = 5 Hz), 153.6, 158.1 (d, JC−F = 248 Hz),
174.3; 19F NMR (CDCl3, 376 MHz) δ − 117.8; HRMS (FAB) m/z
calcd for [C13H11FO3 + H]+ 235.0770, found 235.0775.
found 759.1720; [α]25.8 = +140.9 (c 1.0, CHCl3).
D
3-(1-Hydroxy-5-(4-methylphenylsulfonamido)naphthalen-2-yl)-
propanoic acid (3h). This compound was prepared as 3a−g from N-
(5-hydroxynaphthalen-1-yl)-4-methylbenzenesulfonamide17 in 55%
yield for 3 steps (1.06 g, 2.75 mmol).5a,b Brown solid; TLC, Rf =
0.37 (hexane−EtOAc−CHCl3 = 1:2:1 with a few drops of AcOH); IR
(KBr) 3433, 3244, 1697 cm−1; 1H NMR (DMSO-d6, 400 MHz) δ 2.31
(s, 3H), 2.54 (t, J = 7.8 Hz, 2H), 2.96 (t, J = 7.8 Hz, 2H), 7.08 (d, J =
8.2 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 7.28−7.32 (m, 3H), 7.54 (d, J =
8.7 Hz, 1H), 7.59 (d, J = 8.2 Hz, 2H), 8.05 (d, J = 8.2 Hz, 1H), 9.19
(brs, 1H), 10.06 (s, 1H), 12.19 (brs, 1H); 13C{1H} NMR (DMSO-d6,
100 MHz) δ 21.0, 25.3, 34.2, 114.7, 120.6, 122.0, 122.1, 124.2, 126.4,
126.8, 128.5, 129.4, 129.6, 132.4, 137.5, 143.0, 149.5, 174.3; HRMS
(FAB) m/z calcd for [C20H19NO5S + H]+ 386.1062, found 386.1053.
Representative Experimental Procedures for the Prepara-
tion of 7a−f (7a as an Example).18 To a stirred solution of 2-
naphthol (1.44 g, 10.0 mmol) and amberlyst (1.00 g) in toluene (30.0
mL) was added acrylic acid (1.36 mL, 20.0 mmol) and the resulting
mixture was refluxed overnight. The resulting suspension was filtered
through Celite and the solvents were removed in vacuo. The residue
was purified by flash column chromatography on silica gel (eluent:
hexane−EtOAc = 20:1) to give 1,2-dihydro-3H-benzo[f ]chromen-3-
one (1.78 g, 9.00 mmol, 90% yield). To a solution of this lactone (1.78
g, 9.00 mmol) in THF (40.0 mL) was added 1 M LiOH (30.0 mL),
and the resulting mixture was stirred for 6 h at 25 °C. The resulting
mixture was poured into 1 M HCl (100 mL), and aqueous layer was
separated and extracted with EtOAc (twice). The combined organic
layers were washed with brine and dried over anhydrous Na2SO4, and
solvents were removed in vacuo. The residue was purified by flash
column chromatography on silica gel (eluent: hexane−EtOAc = 4:1 to
1:1) to give 3a (1.95 g, 9.00 mmol) quantitatively.
3-(2-Hydroxy-4-methylnaphthalen-1-yl)propanoic Acid (7e). This
compound was prepared as 7a from 4-methyl-2-naphthol20 in 66%
yield for 2 steps (0.760 g, 3.30 mmol). White solid; TLC, Rf = 0.44
(hexane−EtOAc−CHCl3 = 1:2:1 with a few drops of AcOH); IR
1
(KBr) 3500−3300, 1690 cm−1; H NMR (DMSO-d6, 400 MHz) δ
2.39 (t, J = 8.2 Hz, 2H), 2.55 (s, 3H), 3.17 (t, J = 8.2 Hz, 2H), 7.02 (s,
1H), 7.31 (t, J = 7.8 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.87−7.90 (m,
2H), 9.47 (brs, 1H), 12.10 (brs, 1H); 13C{1H} NMR (DMSO-d6, 100
MHz) δ 19.1, 20.2, 34.0, 115.9, 118.9, 122.2, 122.7, 124.7, 126.1,
127.4, 133.1, 133.5, 151.7, 174.3; HRMS (FAB) m/z calcd for
[C14H14O3 + H]+ 231.1021, found 231.1021.
3-(2-Hydroxy-7-methoxynaphthalen-1-yl)propanoic Acid (7f).
This compound was prepared as 7a from 7-methoxy-2-naphthol in
84% yield for 2 steps (1.03 g, 4.20 mmol). White solid; TLC, Rf = 0.48
(hexane−EtOAc−CHCl3 = 1:2:1 with a few drops of AcOH); IR
1
(KBr) 3500−3200, 1692 cm−1; H NMR (DMSO-d6, 400 MHz) δ
2.45 (t, J = 7.6 Hz, 2H), 3.18 (t, J = 7.6 Hz, 2H), 3.87 (s, 3H), 6.92
(dd, J = 2.8, 8.8 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 2.8 Hz,
1H), 7.54 (d, J = 8.8 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 9.60 (brs, 1H),
12.17 (brs, 1H); 13C{1H} NMR (DMSO-d6, 100 MHz) δ 20.5, 33.6,
55.0, 101.5, 114.4, 115.4, 117.2, 123.5, 127.3, 130.1, 134.2, 153.0,
157.8, 174.6; HRMS (FAB) m/z calcd for [C14H14O4 + H]+ 247.0970,
found 247.0979.
3-(2-Hydroxy-7-(methoxymethoxy)naphthalen-1-yl)propanoic
Acid (7g). To a stirred solution of 9-hydroxy-1,2-dihydro-3H-
benzo[f ]chromen-3-one18 (0.670 g, 3.12 mmol) and (i-Pr)2NEt
(1.10 mL, 6.24 mmol) in CH2Cl2 (30.0 mL) was added
methoxymethyl chloride (0.280 mL, 3.74 mmol) at 0 °C. After
stirring overnight at 25 °C, the resulting mixture was poured into H2O
(10.0 mL). The aqueous layer was separated and extracted with
CHCl3. The combined organic layers were washed with brine and
dried over anhydrous MgSO4, and solvents were removed in vacuo.
The residue was purified by flash column chromatography on silica gel
(eluent: hexane−EtOAc = 10:1 to 4:1) to give methoxymethyl ether
(0.770 g, 2.96 mmol, 95% yield) as a yellow solid. To a solution of this
methoxymethyl ether (0.770 g, 2.96 mmol) in THF (10.0 mL) and
MeOH (10.0 mL) was added 2 M NaOH (10.0 mL), and the resulting
mixture was stirred overnight at 25 °C. The resulting mixture was
poured into 1 M HCl (30.0 mL), and the aqueous layer was separated
and extracted with EtOAc (twice). The combined organic layers were
washed with brine and dried over anhydrous MgSO4, and solvents
were removed in vacuo. The residue was purified by flash column
chromatography on silica gel (eluent: hexane−EtOAc = 4:1 to 1:2) to
give 7g (0.540 g, 1.95 mmol) in 66% yield. Pale yellow solid; TLC, Rf
= 0.41 (hexane−EtOAc−CHCl3 = 1:2:1 with a few drops of AcOH);
3-(2-Hydroxynaphthalen-1-yl)propanoic Acid (7a).10b,18 White
solid; TLC, Rf = 0.52 (hexane−EtOAc−CHCl3 = 1:2:1 with a few
1
drops of AcOH); H NMR (CDCl3, 400 MHz) δ 2.95 (t, J = 6.4 Hz,
2H), 3.33 (t, J = 6.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 8.4
Hz, 1H), 7.50 (t, J = 8.4 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.78 (d, J =
8.4 Hz, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 19.4, 33.5, 117.9,
119.4, 122.0, 123.2, 126.7, 128.7, 128.9, 129.5, 132.7, 151.6, 180.4.
3-(3-Bromo-2-hydroxynaphthalen-1-yl)propanoic Acid (7b). This
compound was prepared as 7a from 3-bromo-2-naphthol in 78% yield
for 2 steps (1.15 g, 3.90 mmol). White solid; TLC, Rf = 0.44 (hexane−
EtOAc−CHCl3 = 1:2:1 with a few drops of AcOH); IR (KBr) 3600−
1
3300, 1696 cm−1; H NMR (DMSO-d6, 400 MHz) δ 2.49 (t, J = 8.0
Hz, 2H), 3.30 (t, J = 8.0 Hz, 2H), 7.36 (t, J = 7.2 Hz, 1H), 7.51 (t, J =
7.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 8.11 (s,
1H), 9.38 (brs, 1H), 12.31 (brs, 1H); 13C{1H} NMR (DMSO-d6, 100
MHz) δ 21.3, 33.8, 114.4, 122.1, 122.8, 123.9, 126.9, 127.7, 129.4,
130.2, 131.8, 148.3, 174.4; HRMS (FAB) m/z calcd for [C13H11BrO3
+ H]+ 294.9970, found 294.9967.
1
IR (KBr) 3500−3000, 1682 cm−1; H NMR (CDCl3, 400 MHz) δ
3-(6-Bromo-2-hydroxynaphthalen-1-yl)propanoic Acid (7c). This
compound was prepared as 7a from 6-bromo-2-naphthol in 21% yield
for 2 steps (0.310 g, 1.05 mmol). White solid; TLC, Rf = 0.44
(hexane−EtOAc−CHCl3 = 1:2:1 with a few drops of AcOH); IR
2.95 (t, J = 6.4 Hz, 2H), 3.27 (t, J = 6.4 Hz, 2H), 3.54 (s, 3H), 5.31 (s,
2H), 7.04 (d, J = 8.7 Hz, 1H), 7.11 (dd, J = 2.4, 8.7 Hz, 1H), 7.31 (d, J
= 2.4 Hz, 1H), 7.52 (brs, 1H), 7.60 (d, J = 8.7 Hz, 1H), 7.71 (d, J = 8.7
Hz, 1H), 9.10 (brs, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 19.5,
33.2, 56.1, 94.5, 105.7, 115.3, 117.2, 117.5, 125.4, 128.4, 130.4, 134.0,
152.3, 155.8, 180.2; HRMS (FAB) m/z calcd for [C15H16O5 + H]+
277.1076, found 277.1080.
3-(7-(Benzyloxy)-2-hydroxynaphthalen-1-yl)propanoic Acid (7h).
To a stirred solution of 9-hydroxy-1,2-dihydro-3H-benzo[f ]chromen-
3-one18 (1.50 g, 7.00 mmol), K2CO3 (1.45 g, 10.5 mmol) and
tetrabutylammonium iodide (0.260 g, 0.700 mmol) in acetone (70.0
mL) was added benzyl bromide (1.00 mL, 8.40 mmol) at 25 °C, and
the resulting mixture was refluxed for 4 h. The solvents were removed
in vacuo. To the residue was added H2O (40.0 mL), and the aqueous
layer was separated and extracted with EtOAc. The combined organic
layers were washed with brine and dried over anhydrous MgSO4, and
solvents were removed in vacuo. The residue was purified by flash
1
(KBr) 3500−3200, 1703 cm−1; H NMR (DMSO-d6, 400 MHz) δ
2.40 (t, J = 8.0 Hz, 2H), 3.18 (t, J = 8.0 Hz, 2H), 7.20 (d, J = 9.2 Hz,
1H), 7.52 (d, J = 9.2 Hz, 1H), 7.64 (d, J = 9.2 Hz, 1H), 7.84 (d, J = 9.2
Hz, 1H), 8.03 (s, 1H), 9.85 (brs, 1H), 12.19 (brs, 1H); 13C{1H} NMR
(DMSO-d6, 100 MHz) δ 20.3, 33.7, 115.2, 118.4, 119.2, 124.9, 126.9,
129.0, 129.5, 130.1, 131.5, 152.9, 174.2; HRMS (FAB) m/z calcd for
[C13H11BrO3 + H]+ 294.9970, found 294.9966.
3-(8-Fluoro-2-hydroxynaphthalen-1-yl)propanoic Acid (7d). This
compound was prepared as 7a from 8-fluoro-2-naphthol19 in 69% yield
for 2 steps (0.808 g, 3.45 mmol). White solid; TLC, Rf = 0.48
(hexane−EtOAc−CHCl3 = 1:2:1 with a few drops of AcOH); IR
1
(KBr) 3500−3200, 1685 cm−1; H NMR (DMSO-d6, 400 MHz) δ
2.43 (t, J = 8.2 Hz, 2H), 3.28−3.32 (m, 2H), 7.17−7.24 (m, 3H), 7.60
D
DOI: 10.1021/acs.joc.7b01941
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
column chromatography on silica gel (eluent: hexane−EtOAc = 10:1
to 5:1) to give benzyl ether (2.13 g, 7.00 mmol, > 99% yield). To a
solution of this benzyl ether (2.13 g, 7.00 mmol) in THF (30.0 mL)
and MeOH (30.0 mL) was added 2 M NaOH (30.0 mL) and the
resulting mixture was stirred overnight at 25 °C. The resulting mixture
was poured into 1 M HCl (100 mL), and the aqueous layer was
separated and extracted with EtOAc (twice). The combined organic
layers were washed with brine and dried over anhydrous MgSO4, and
solvents were removed in vacuo. The residue was purified by flash
column chromatography on silica gel (eluent: hexane−EtOAc = 4:1 to
1:2) to give 8h (1.69 g, 5.25 mmol) in 75% yield. Pale yellow solid;
TLC, Rf = 0.48 (hexane−EtOAc−CHCl3 = 1:2:1 with a few drops of
AcOH); IR (KBr) 3400−3000, 1685 cm−1; 1H NMR (DMSO-d6, 400
MHz) δ 2.36 (t, J = 7.8 Hz, 2H), 3.17 (t, J = 7.8 Hz, 2H), 5.24 (s, 2H),
6.98−7.00 (m, 2H), 7.28 (d, J = 2.3 Hz, 1H), 7.33 (t, J = 7.3 Hz, 1H),
7.40 (t, J = 7.3 Hz, 2H), 7.51−7.55 (m, 3H), 7.68 (d, J = 9.2 Hz, 1H),
9.58 (brs, 1H), 12.17 (brs, 1H); 13C{1H} NMR (DMSO-d6, 100
MHz) δ 20.4, 33.5, 69.2, 103.0, 114.7, 115.5, 117.1, 123.6, 127.2,
127.9, 128.5, 130.0, 134.1, 137.2, 152.9, 156.7, 174.4; HRMS (FAB)
m/z calcd for [C20H18O4 + H]+ 323.1283, found 323.1286.
3-(6-Cyano-2-hydroxynaphthalen-1-yl)propanoic Acid (7i). This
compound was prepared as 3a−g from 6-cyano-2-naphthol in 73%
yield for 3 steps (0.881 g, 3.65 mmol).5a,b White solid; TLC, Rf = 0.29
(Hexane−EtOAc−AcOH = 10:10:1); IR (KBr) 3350−3150, 1633
cm−1; 1H NMR (DMSO-d6, 400 MHz) δ 2.42 (t, J = 7.8 Hz, 2H), 3.18
(t, J = 7.8 Hz, 2H), 7.31 (d, J = 8.7 Hz, 1H), 7.69 (dd, J = 1.4, 8.7 Hz,
1H), 7.82 (d, J = 8.7 Hz, 1H), 8.04 (d, J = 8.7 Hz, 1H), 8.41 (d, J = 1.4
Hz, 1H), 10.33 (brs, 1H), 12.19 (brs, 1H); 13C{1H} NMR (DMSO-d6,
100 MHz) δ 20.2, 33.6, 104.3, 118.7, 119.6, 119.7, 124.0, 126.6, 127.0,
128.7, 134.6, 134.8, 155.5, 174.1; HRMS (FAB) m/z calcd for
[C14H11NO3 + H]+ 242.0812, found 242.0806.
(CDCl3, 100 MHz) δ 26.5, 31.2, 84.2, 122.5, 127.0, 128.0, 128.8,
130.1, 133.4, 135.1, 135.9, 175.7, 194.7; HPLC (OD-H column),
Hexane−EtOH = 10:1 as eluent, 1.0 mL/min, tR = 24.7 min, tS = 28.4
min.
(S)-4′-Phenyl-1′H,3H-spiro[furan-2,2′-naphthalene]-1′,5(4H)-
dione (4d).5 90% yield (0.0261 g, 0.0899 mmol), 96% ee. Colorless
1
crystal; H NMR (CDCl3, 400 MHz) δ 2.27 (ddd, J = 9.6, 11.0, 13.3
Hz, 1H), 2.54 (ddd, J = 2.3, 9.6, 13.3 Hz, 1H), 2.63 (ddd, J = 2.3, 9.6,
17.6 Hz, 1H), 2.93 (ddd, J = 9.6, 11.0, 17.6 Hz, 1H), 6.12 (s, 1H), 7.15
(d, J = 7.3 Hz, 1H), 7.34−7.50 (m, 6H), 7.56 (dt, J = 1.4, 7.3 Hz, 1H),
8.10 (dd, J = 1.4, 7.3 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ
26.7, 31.5, 83.7, 127.4, 127.6, 128.2, 128.4, 128.6, 128.7, 128.9, 130.6,
135.3, 137.4, 137.6, 139.8, 176.3, 196.4; HPLC (OD-H column),
Hexane−EtOH = 10:1 as eluent, 1.0 mL/min, tS = 21.7 min, tR = 27.1
min.
(S)-4′-(4-Bromobenzoyl)-1′H,3H-spiro[furan-2,2′-naphthalene]-
1′,5(4H)-dione (4e).5 99% yield (0.0393 g, 0.0989 mmol), 96% ee.
1
White solid; H NMR (CDCl3, 400 MHz) δ 2.27 (ddd, J = 9.6, 11.0,
13.3 Hz, 1H), 2.52 (ddd, J = 1.8, 9.6, 13.3 Hz, 1H), 2.63 (ddd, J = 1.8,
9.6, 17.6 Hz, 1H), 2.92 (ddd, J = 9.6, 11.0, 17.6 Hz, 1H), 6.38 (s, 1H),
7.37 (d, J = 7.8 Hz, 1H), 7.50 (dt, J = 0.9, 7.8 Hz, 1H), 7.60−7.66 (m,
3H), 7.83 (d, J = 8.7 Hz, 1H), 8.12 (dd, J = 1.4, 7.8 Hz, 1H); 13C{1H}
NMR (CDCl3, 100 MHz) δ 26.2, 31.2, 82.5, 126.8, 127.3, 128.6, 129.8,
129.9, 131.4, 132.3, 133.7, 134.2, 134.7, 135.8, 137.2, 175.7, 193.5,
195.0; HPLC (IA-3 column), Hexane−EtOH = 4:1 as eluent, 1.0 mL/
min, tR = 30.9 min, tS = 33.0 min.
(S)-3′-(Benzyloxymethyl)-1′H,3H-spiro[furan-2,2′-naphthalene]-
1′,5(4H)-dione (4f).5a,b 74% yield (0.0247 g, 0.0739 mmol), 97% ee.
1
Colorless amorphous; H NMR (CDCl3, 400 MHz) δ 2.30−2.37 (m,
1H), 2.43−2.55 (m, 2H), 2.69−2.79 (m, 1H), 4.25 (d, J = 12.8 Hz,
1H), 4.36 (d, J = 12.8 Hz, 1H), 4.60 (s, 2H), 6.70 (s, 1H), 7.25 (d, J =
7.8 Hz, 1H) 7.30−7.40 (m, 6H), 7.62 (t, J = 7.8 Hz, 1H), 7.98 (d, J =
7.8 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 26.1, 30.4, 68.9,
73.3, 85.8, 124.6, 126.7, 127.7, 127.8(2C), 128.0, 128.5, 128.6 135.6,
136.8, 137.5, 140.0, 176.6, 196.9; HPLC (OD-H column), Hexane−i-
PrOH = 85:15 as eluent, 1.0 mL/min, tS = 20.8 min, tR = 38.3 min.
(S)-6′-Methoxy-1′H,3H-spiro[furan-2,2′-naphthalene]-1′,5(4H)-
dione (4g).5a,b 73% yield (0.0178 g, 0.0729 mmol), 97% ee. White
solid; 1H NMR (CDCl3, 400 MHz) δ 2.17 (ddd, J = 9.6, 11.0, 13.3 Hz,
1H), 2.40 (ddd, J = 2.2, 9.6, 13.3 Hz, 1H), 2.61 (ddd, J = 2.2, 9.6, 17.6
Hz, 1H), 2.95 (ddd, J = 9.6, 11.0, 17.6 Hz, 1H), 3.94 (s, 3H), 6.21 (d, J
= 9.6 Hz, 1H), 6.60 (d, J = 9.6 Hz, 1H), 6.72 (d, J = 2.8 Hz, 1H), 6.91
(dd, J = 2.8, 8.7 Hz, 1H), 8.01 (d, J = 8.7 Hz, 1H); 13C{1H} NMR
(CDCl3, 100 MHz) δ 26.8, 31.6, 55.7, 82.8, 112.9, 114.2, 120.6, 127.9,
130.5, 133.3, 139.1, 165.6, 176.3, 194.8; HPLC (AD-H column),
Hexane−i-PrOH = 85:15 as eluent, 1.0 mL/min, tS = 30.7 min, tR =
35.6 min.
Representative Procedure for the Enantioselective Syn-
thesis of 4 (4a as an Example). A solution of 3a (0.0216 g, 0.100
mmol), 2a (3.20 mg, 0.005 mmol, 5 mol %), purified m-CPBA (>99%
purity; 0.0207 g, 0.120 mmol, 1.2 equiv) and EtOH (0.0350 mL, 0.600
mmol, 6 equiv) in DCE (5.00 mL) was stirred at −20 °C. After 36 h,
the resulting mixture was poured into aqueous Na2S2O3 (5 mL) and
aqueous NaHCO3. The aqueous layer was separated and extracted
with CHCl3 (2 times). The combined organic layers were dried over
anhydrous MgSO4 and solvents were removed in vacuo. The residue
was purified by flash column chromatography on silica gel (eluent:
hexane−EtOAc = 10:1 to 4:1) to give 4a5 (0.0184 g, 0.0860 mmol) in
86% yield. Enantiomeric excess of 4a was determined to be 98% ee by
HPLC analysis.
(S)-1′H,3H-Spiro[furan-2,2′-naphthalene]-1′,5(4H)-dione (4a).5a,b
1
White solid; H NMR (CDCl3, 400 MHz) δ 2.18 (ddd, J = 9.6, 11.0,
13.5 Hz, 1H), 2.49 (ddd, J = 1.8, 9.6, 13.5 Hz, 1H), 2.60 (ddd, J = 1.8,
9.6, 17.6 Hz, 1H), 2.92 (ddd, J = 9.6, 11.0, 17.6 Hz, 1H), 6.21 (d, J =
10.4 Hz, 1H), 6.66 (d, J = 10.4 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.41
(t, J = 8.0 Hz, 1H), 7.62 (t, J = 8.0 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H);
13C{1H} NMR (CDCl3, 100 MHz) δ 26.5, 31.2, 83.4, 127.3, 127.8,
127.9, 127.9, 129.0, 132.3, 135.7, 136.8, 176.5, 196.5; HPLC (OD-H
column), Hexane−EtOH = 10:1 as eluent, 1.0 mL/min, tR = 23.4 min,
tS = 27.6 min.
(S)-4′-Chlorospiro[tetrahydrofuran-2,2′-(1′H-naphthaline)]-1′,5-
dione (4b).5 93% yield (0.0231 g, 0.0929 mmol), 98% ee. White solid;
1H NMR (CDCl3, 400 MHz) δ 2.23 (ddd, J = 9.6, 11.0, 13.4 Hz, 1H),
2.45 (ddd, J = 2.3, 9.6, 13.4 Hz, 1H), 2.62 (ddd, J = 2.3, 9.6, 17.9 Hz,
1H), 2.91 (ddd, J = 9.6, 11.0, 17.9 Hz, 1H), 6.40 (s, 1H), 7.52 (dt, J =
1.8, 7.4 Hz, 1H), 7.70−7.79 (m, 2H), 8.06 (d, J = 7.4 Hz, 1H);
13C{1H} NMR (CDCl3, 100 MHz) δ 26.5, 31.5, 83.4, 126.1, 127.3,
(S)-N-(1′,5-Dioxo-4,5-dihydro-1′H,3H-spiro[furan-2,2′-naphtha-
len]-5′-yl)-4-methylbenzenesulfonamide (4h). 56% yield (0.0215 g,
0.0561 mmol), 91% ee. Yellow solid; TLC, Rf1= 0.57 (hexane−EtOAc
= 1:2); IR (KBr) 3254, 1786, 1693 cm−1; H NMR (CDCl3, 400
MHz) δ 2.08−2.17 (m, 1H), 2.32−2.38 (m, 1H), 2.42 (s, 3H), 2.58
(ddd, J = 1.8, 9.6. 17.8 Hz, 1H), 2.80−2.90 (m, 1H), 6.12 (d, J = 10.6
Hz, 1H), 6.74 (d, J = 10.6 Hz, 1H), 6.76 (s, 1H), 7.25−7.36 (m, 4H),
7.55 (d, J = 8.3 Hz, 2H), 7.90 (d, J = 6.9 Hz, 1H); 13C{1H} NMR
(CDCl3, 100 MHz) δ 21.6, 26.4, 31.2, 82.9, 122.1, 127.0, 127.3, 128.3,
129.2, 129.9, 132.3, 132.8, 133.3, 134.5, 135.6, 144.5, 176.3, 196.0;
HPLC (IA-3 column), Hexane−EtOH = 2:1 as eluent, 0.7 mL/min, tR
= 47.0 min, tS = 75.1 min; HRMS (FAB) m/z calcd for [C20H17NO5S
+ H]+ 384.0906, found 384.0902; [α]27.9D = −48.5 (c 0.80, CHCl3) for
91% ee.
128.1, 129.1, 130.1, 131.8, 134.5, 135.8, 175.7, 194.7; HPLC (OD-H
column), Hexane−EtOH = 10:1 as eluent, 1.0 mL/min, tR = 23.4 min,
tS = 25.7 min.
(S)-4′-Bromospiro[tetrahydrofuran-2,2′-(1′H-naphthaline)]-1′,5-
dione (4c).5 99% yield (0.0290 g, 0.0989 mmol), 95% ee. White solid;
1H NMR (CDCl3, 400 MHz) δ 2.24 (ddd, J = 9.6, 11.0, 13.5 Hz, 1H),
2.46 (ddd, J = 2.3, 9.6, 13.5 Hz, 1H), 2.62 (ddd, J = 2.3, 9.6, 17.9 Hz,
1H), 2.90 (ddd, J = 9.6, 11.0, 17.9 Hz, 1H), 6.67 (s, 1H), 7.49−7.53
(m, 1H), 7.73−7.78 (m, 2H), 8.05 (d, J = 7.2 Hz, 1H); 13C{1H} NMR
Representative Procedure for the Enantioselective Syn-
thesis of 8 (8a as an Example). A solution of 7a (0.0216 g, 0.100
mmol), 2a (3.20 mg, 0.005 mmol, 5 mol %), purified m-CPBA (>99%
purity; 0.0207 g, 0.120 mmol, 1.2 equiv) and HFIP (0.526 mL, 5.000
mmol, 5 equiv) in dichloromethane (5.00 mL) was stirred at −20 °C.
After 15 h, the resulting mixture was poured into aqueous Na2S2O3 (5
mL) and aqueous NaHCO3. The aqueous layer was separated and
extracted with CHCl3 (2 times). The combined organic layers were
dried over anhydrous MgSO4 and solvents were removed in vacuo.
E
DOI: 10.1021/acs.joc.7b01941
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
The residue was purified by flash column chromatography on silica gel
(eluent: hexane−EtOAc = 10:1 to 4:1) to give 8a (0.0191 g, 0.0891
mmol) in 89% yield. Enantiomeric excess of 8a was determined to be
94% ee by HPLC analysis.
26.5, 36.1, 55.7, 86.0, 111.5, 114.4, 119.7, 122.1, 131.5, 143.0, 146.0,
162.1, 176.5, 197.5; HRMS (FAB) m/z calcd for [C14H12O4 + H]+
245.0814, found 245.0808; HPLC (OD-H column), Hexane−EtOH =
10:1 as eluent, 1.0 mL/min, tS = 32.5 min, tR = 41.0 min; [α]25.3
−327.6 (c 1.2, CHCl3) for 89% ee.
=
D
(S)-2′H,3H-Spiro[furan-2,1′-naphthalene]-2′,5(4H)-dione (8a).10
White solid; TLC, Rf = 0.70 (hexane−EtOAc = 1:2); 1H NMR
(CDCl3, 400 MHz) δ 2.11−2.20 (m, 1H), 2.62−2.70 (m, 2H), 2.81−
2.91 (m, 1H), 6.18 (d, J = 9.6 Hz, 1H), 7.36 (dd, J = 1.6, 7.6 Hz, 1H),
7.41 (dt, J = 1.6, 7.6 Hz, 1H), 7.46−7.50 (m, 2H), 7.56 (d, J = 7.6 Hz,
1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 26.5, 35.7, 85.8, 122.4,
125.6, 129.0, 129.1, 129.7, 131.0, 140.4, 146.0, 176.4, 197.5; HPLC
(OD-H column), Hexane−EtOH = 10:1 as eluent, 1.0 mL/min, tS =
26.2 min, tR = 40.2 min; [α]23.0D = −340.0 (c 1.4, CHCl3) for 95% ee.
(S)-3′-Bromo-2′H,3H-spiro[furan-2,1′-naphthalene]-2′,5(4H)-
dione (8b).10a 85% yield (0.0249 g, 0.0849 mmol), 89% ee. Optically
pure (S)-8b (99% ee) was obtained after a single recrystallization from
hexane/ethanol at 0 °C. Colorless crystal; Mp: 117−119 °C; TLC, Rf
= 0.57 (hexane−EtOAc = 1:2); 1H NMR (CDCl3, 400 MHz) δ 2.15−
2.23 (m, 1H), 2.64−2.72 (m, 2H), 2.82−2.92 (m, 1H), 7.33 (d, J = 7.2
Hz, 1H), 7.42 (dt, J = 1.6, 7.2 Hz, 1H), 7.51 (dt, J = 1.6, 7.2 Hz, 1H),
7.55 (dd, J = 1.6, 7.2 Hz, 1H), 7.92 (s, 1H); 13C{1H} NMR (CDCl3,
100 MHz) δ 26.4, 36.1, 86.4, 118.2, 126.0, 128.8, 129.4, 129.6, 131.4,
139.9, 147.3, 175.9, 191.2; HPLC (OD-H column), Hexane−EtOH =
(S)-7′-(Methoxymethoxy)-2′H,3H-spiro[furan-2,1′-naphthalene]-
2′,5(4H)-dione (8g). 85% yield (0.0233 g, 0.0849 mmol), 91% ee.
Yellow solid; TLC, Rf = 0.50 (hexane−EtOAc = 1:2); IR (KBr) 1786,
1675 cm−1; 1H NMR (CDCl3, 400 MHz) δ 2.05−2.19 (m, 1H), 2.61−
2.69 (m, 2H), 2.79−2.89 (m, 1H), 3.48 (s, 3H), 5.19 (d, J = 6.9 Hz,
1H), 5.25 (d, J = 6.9 Hz, 1H), 6.06 (d, J = 9.6 Hz, 1H), 7.04 (dd, J =
2.8, 8.7 Hz, 1H), 7.20 (d, J = 2.8 Hz, 1H), 7.26 (d, J = 8.7 Hz, 1H),
7.43 (d, J = 9.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 26.5,
36.0, 56.3, 85.8, 94.1, 114.0, 116.0, 120.2, 123.1, 131.4, 142.8, 145.8,
159.6, 176.4, 197.4; HRMS (FAB) m/z calcd for [C15H14O5 + H]+
275.0919, found 275.0921; HPLC (IA-3 column), Hexane−EtOH =
4:1 as eluent, 1.0 mL/min, tS = 33.1 min, tR = 45.1 min; [α]27.9
−239.8 (c 1.7, CHCl3) for 91% ee.
=
D
(S)-7′-(Benzyloxy)-2′H,3H-spiro[furan-2,1′-naphthalene]-
2′,5(4H)-dione (8h). 57% yield (0.0183 g, 0.0571 mmol), 87% ee.
Yellow solid; TLC, Rf = 0.63 (hexane−EtOAc = 1:2); IR (KBr) 1786,
1673 cm−1; 1H NMR (CDCl3, 400 MHz) δ 2.06−2.15 (m, 1H), 2.58−
2.68 (m, 2H), 2.78−2.88 (m, 1H), 5.12 (s, 2H), 6.04 (d, J = 10.1 Hz,
1H), 6.95 (dd, J = 2.3, 8.2 Hz, 1H), 7.17 (d, J = 2.3 Hz, 1H), 7.27 (d, J
= 8.2 Hz, 1H), 7.32−7.44 (m, 6H); 13C{1H} NMR (CDCl3, 100
MHz) δ 26.5, 36.1, 70.4, 85.9, 112.6, 115.1, 119.9, 122.4, 127.5, 128.3,
128.7, 131.5, 135.9, 143.0, 145.9, 161.2, 176.4, 197.4; HRMS (FAB)
m/z calcd for [C20H16O4 + H]+ 321.1127, found 321.1124; HPLC
(OD-H column), Hexane−EtOH = 4:1 as eluent, 1.0 mL/min, tS =
16.3 min, tR = 20.0 min; [α]25.2D = −197.7 (c 1.8, CHCl3) for 87% ee.
(S)-2′,5-Dioxo-4,5-dihydro-2′H,3H-spiro[furan-2,1′-naphtha-
lene]-6′-carbonitrile (8i). 99% yield (0.0237 g, 0.0991 mmol), 95% ee.
White solid; TLC, Rf = 0.30 (Hexane−EtOAc = 1:1); IR (CHCl3)
2237, 1800, 1693 cm−1; 1H NMR (CDCl3, 400 MHz) δ 2.04−2.20 (m,
1H), 2.65−2.73 (m, 2H), 2.78−2.89 (m, 1H), 6.32 (d, J = 9.6 Hz,
1H), 7.49 (d, J = 9.6 Hz, 1H), 7.68 (s, 1H), 7.71 (d, J = 8.2 Hz, 1H),
7.77 (d, J = 8.2 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 26.2,
35.5, 85.2, 113.5, 117.4, 124.5, 126.6, 130.3, 132.6, 134.0, 143.4, 145.0,
175.5, 195.8; HRMS (FAB) m/z calcd for [C14H9NO3 + H]+
240.0655, found 240.0657; HPLC (OD-H column), Hexane−EtOH
10:1 as eluent, 1.0 mL/min, tS = 29.5 min, tR = 42.2 min; [α]22.9
−197.8 (c 1.0, CHCl3) for 99% ee.
=
D
(S)-6′-Bromo-2′H,3H-spiro[furan-2,1′-naphthalene]-2′,5(4H)-
dione (8c). 95% yield (0.0279 g, 0.0952 mmol), 95% ee. White solid;
TLC, Rf = 0.57 (hexane−EtOAc = 1:2); IR (KBr) 1788, 1683 cm−1;
1H NMR (CDCl3, 400 MHz) δ 2.08−2.17 (m, 1H), 2.62−2.69 (m,
2H), 2.79−2.89 (m, 1H), 6.22 (d, J = 9.6 Hz, 1H), 7.41 (d, J = 9.6 Hz,
1H), 7.44 (d, J = 8.4 Hz, 1H), 7.51 (d, J = 1.8 Hz, 1H), 7.60 (dd, J =
1.8, 8.4 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 26.4, 35.6,
85.4, 123.1, 123.8, 127.4, 130.9, 132.3, 133.7, 139.2, 144.4, 176.0,
196.7; HRMS (FAB) m/z calcd for [C13H9BrO3 + H]+ 292.9813,
found 292.9814; HPLC (OD-H column), Hexane−EtOH = 10:1 as
eluent, 1.0 mL/min, tS = 29.6 min, tR = 36.7 min; [α]23.9D = −142.8 (c
1.4, CHCl3) for 95% ee.
(S)-8′-Fluoro-2′H,3H-spiro[furan-2,1′-naphthalene]-2′,5(4H)-
dione (8d). 92% yield (0.0213 g, 0.0918 mmol), 95% ee. White solid;
TLC, Rf = 0.57 (hexane−EtOAc = 1:2); IR (KBr) 1787, 1674 cm−1;
1H NMR (CDCl3, 400 MHz) δ 2.41−2.56 (m, 2H), 2.78 (ddd, J = 3.2,
= 2:1 as eluent, 0.8 mL/min, tS = 19.5 min, tR = 25.6 min; [α]22.3
−157.8 (c 2.1, CHCl3) for 95% ee.
=
D
10.1, 17.4 Hz, 1H), 2.99 (dt, J = 10.6, 17.4 Hz, 1H), 6.23 (d, J = 10.1
Hz, 1H), 7.16−7.21 (m, 2H), 7.41−7.46 (m, 1H), 7.48 (dd, J = 1.8,
10.1 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 27.1, 32.6, 81.0,
(1′S,2′R,3′S,4′R)-3′-Bromo-2′,4′-dihydroxy-3′,4′-dihydro-2′H,3H-
spiro[furan-2,1′-naphthalen]-5(4H)-one ((+)-9). To a solution of
(S)-8a (0.214 g, 1.00 mmol, 89% ee) and CeCl3·7H2O (0.373 g, 1.00
mmol) in MeOH (25.0 mL) and THF (25.0 mL) was added NaBH4
(0.0380 g, 1.00 mmol) at −78 °C. After stirring for 15 min at same
temperature, the reaction mixture was diluted with EtOAc and washed
with 1 M HCl and brine. The combined organic layers were dried over
anhydrous MgSO4 and the solvents were removed in vacuo. The
residue was purified by flash column chromatography on silica gel
(eluent: hexane−EtOAc = 10:1 to 4:1) to give (1′S,2′S)-2′-hydroxy-
2′H,3H-spiro[furan-2,1′-naphthalen]-5(4H)-one (0.205 g, 0.950
mmol, 95% yield) as a white solid. TLC, Rf = 0.72 (hexane−EtOAc
118.8 (d, JC−F = 22 Hz), 123.8, 125.8 (d, JC−F = 3 Hz), 126.2 (d, JC−F
=
10 Hz), 131.3, 131.4, 145.5 (d, JC−F = 4 Hz), 161.5, (d, JC−F = 251
Hz), 176.4, 196.3; 19F NMR (CDCl3, 376 MHz) δ − 111.5; HRMS
(FAB) m/z calcd for [C13H9FO3 + H]+ 233.0614, found 233.0620;
HPLC (IA-3 column), Hexane−EtOH = 4:1 as eluent, 1.0 mL/min, tR
= 19.9 min, tS = 22.5 min; [α]23.1 = −145.3 (c 1.8, CHCl3) for 95%
D
ee.
(S)-4′-Methyl-2′H,3H-spiro[furan-2,1′-naphthalene]-2′,5(4H)-
dione (8e). 83% yield (0.0190 g, 0.0832 mmol), 95% ee. White solid;
TLC, Rf = 0.57 (hexane−EtOAc = 1:2); IR (KBr) 1786, 1673 cm−1;
1H NMR (CDCl3, 400 MHz) δ 2.10−2.19 (m, 1H), 2.40 (s, 3H),
1
= 1:2); IR (KBr) 3600−3250, 1772 cm−1; H NMR (CDCl3, 400
2.56−2.68 (m, 2H), 2.81−2.91 (m, 1H), 6.11 (s, 1H), 7.43 (dt, J = 1.4,
7.3 Hz, 1H), 7.49 (dt, J = 1.4, 7.3 Hz, 1H), 7.56−7.58 (m, 2H);
13C{1H} NMR (CDCl3, 100 MHz) δ 20.5, 26.8, 36.1, 85.7, 122.0,
125.6, 126.0, 128.9, 130.4, 130.8, 140.3, 154.0, 176.5, 196.7; HRMS
(FAB) m/z calcd for [C14H12O3 + H]+ 229.0865, found 229.0871;
HPLC (IA-3 column), Hexane−EtOH = 4:1 as eluent, 1.0 mL/min, tR
MHz) δ 1.87 (ddd, J = 6.4, 10.5, 13.1 Hz, 1H), 2.50−2.65 (m, 2H),
2.70−2.78 (m, 1H), 3.09 (ddd, J = 7.3, 10.5, 13.1 Hz, 1H), 5.04−5.06
(m, 1H), 5.90 (dd, J = 1.8, 9.6 Hz, 1H), 6.41 (dd, J = 2.8, 9.6 Hz, 1H),
7.09−7.12 (m, 1H), 7.23−7.34 (m, 3H); 13C{1H} NMR (CDCl3, 100
MHz) δ 27.0, 29.0, 73.1, 91.2, 122.8, 126.8, 127.6, 128.3, 128.5, 130.7,
131.7, 137.8, 178.4; HRMS (FAB) m/z calcd for [C13H12O3 + H]+
217.0865, found 217.0868; [α]24.3 = −22.9 (c 0.7, CHCl3) for 89%
= 17.4 min, tS = 18.8 min; [α]28.7 = −333.3 (c 1.6, CHCl3) for 95%
D
D
ee.
ee.
To a solution of this allylic alcohol (0.0360 g, 0.170 mmol) in THF
(1.70 mL) and H2O (1.70 mL) was added NBS (recrystallized, 0.0590
g, 0.340 mmol) at 0 °C. After stirring for 6 h at 0 °C, the resulting
mixture was poured into aqueous Na2S2O3 (5 mL) and the aqueous
layer was separated and extracted with EtOAc (twice). The combined
organic layers were dried over anhydrous MgSO4 and solvents were
removed in vacuo. The residue was purified by flash column
(S)-7′-Methoxy-2′H,3H-spiro[furan-2,1′-naphthalene]-2′,5(4H)-
dione (8f). 51% yield (0.0125 g, 0.0512 mmol), 89% ee. White solid;
TLC, Rf = 0.60 (hexane−EtOAc = 1:2); IR (KBr) 1786, 1682 cm−1;
1H NMR (CDCl3, 400 MHz) δ 2.09−2.18 (m, 1H), 2.61−2.70 (m,
2H), 2.79−2.89 (m, 1H), 3.87 (s, 3H), 6.04 (d, J = 9.6 Hz, 1H), 6.88
(dd, J = 1.8, 8.7 Hz, 1H), 7.08 (d, J = 1.8 Hz, 1H), 7.28 (d, J = 8.7 Hz,
1H), 7.43 (d, J = 9.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ
F
DOI: 10.1021/acs.joc.7b01941
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The Journal of Organic Chemistry
Note
chromatography on silica gel (eluent: hexane−EtOAc = 10:1 to 3:2) to
give 9 (0.0500 g, 0.160 mmol, 94% yield) as a white solid.
Enantiomeric excess of 9 was determined to be 89% ee by HPLC
analysis. Optically pure (+)-9 (>99% ee) was obtained after a single
recrystallization from hexane/ethanol at 0 °C. Colorless crystal; Mp:
165−167 °C; TLC, Rf = 0.57 (hexane−EtOAc = 1:2); IR (KBr)
2015, 47, 587−603. (g) Basdevant, B.; Guilbault, A.-A.; Beaulieu, S.;
Lauriers, A. J.-D.; Legault, C. Y. Pure Appl. Chem. 2017, 89, 781−789.
(3) For recent examples of enantioselective oxidations using chiral
hypervalent iodine catalysts, see: (a) Altermann, S. M.; Richardson, R.
D.; Page, T. K.; Schmidt, R. K.; Holland, E.; Mohammed, U.; Paradine,
S. M.; French, A. N.; Richter, C.; Bahar, A. M.; Witulski, B.; Wirth, T.
Eur. J. Org. Chem. 2008, 2008, 5315. (b) Quideau, S.; Lyvinec, G.;
Marguerit, M.; Bathany, K.; Ozanne-Beaudenon, A.; Buffeteau, T.;
Cavagnat, D.; Chenede, A. Angew. Chem., Int. Ed. 2009, 48, 4605−
4609. (c) Shimogaki, M.; Fujita, M.; Sugimura, T. Eur. J. Org. Chem.
2013, 2013, 7128−7138. (d) Basdevant, B.; Legault, C. L. Org. Lett.
2015, 17, 4918−4921. (e) Murray, S. J.; Ibrahim, H. Chem. Commun.
2015, 51, 2376−2379. (f) Zhang, D.-Y.; Xu, L.; Wu, H.; Gong, L.-Z.
1
3600−3250, 1739 cm−1; H NMR (CD3CN, 400 MHz) δ 2.51−2.58
(m, 1H), 2.72−2.90 (m, 3H), 4.01 (d, J = 7.3 Hz, 1H), 4.20 (d, J = 5.5
Hz, 1H), 4.37 (dd, J = 2.3, 5.5 Hz, 1H), 4.52 (dd, J = 2.3, 7.3 Hz, 1H),
4.95 (t, J = 7.3 Hz, 1H), 7.38−7.56 (m, 4H); 13C{1H} NMR (CD3CN,
100 MHz) δ 29.9, 31.0, 58.7, 72.0, 74.6, 87.6, 128.2, 129.2, 129.7,
130.2, 136.2, 138.6, 177.0; HRMS (FAB) m/z calcd for [C13H13BrO4
+ H]+ 313.0075, found 313.0070; HPLC (IA-3 column), Hexane−
EtOH = 1:1 as eluent, 0.7 mL/min, t1 = 9.2 min, t2 = 11.7 min; [α]26.2
D
Chem. - Eur. J. 2015, 21, 10314−10317. (g) Haubenreisser, S.; Woste,
̈
= 134.3 (c 1.3, CH3CN) for >99% ee.
T. H.; Martínez, C.; Ishihara, K.; Muniz, K. Angew. Chem., Int. Ed.
̃
́
2016, 55, 413−417. (h) Monar, I. G.; Gilmour, R. J. Am. Chem. Soc.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.7b01941.
2016, 138, 5004−5007. (i) Banik, S. M.; Medley, J. W.; Jacobsen, E. N.
Science 2016, 353, 51−54. (j) Gelis, C.; Dumoulin, A.; Bekkaye, M.;
■
S
Neuville, L.; Masson, G. Org. Lett. 2017, 19, 278−281. (k) Muniz, K.;
̃
Barreiro, L.; Romero, R. M.; Martínez, C. J. Am. Chem. Soc. 2017, 139,
4354−4357. (l) Jain, N.; Xu, S.; Ciufolini, M. A. Chem. - Eur. J. 2017,
23, 4542−4546.
Additional experiments, HPLC analysis of products 4, 8
and 9, spectral data for new compounds, and crystal data
and structure refinement for 8b and 9 (PDF)
Crystal data for 8b (CIF)
(4) (a) Dohi, T.; Maruyama, A.; Takenaga, N.; Senami, K.;
Minamitsuji, Y.; Fujioka, H.; Caemmerer, S. B.; Kita, Y. Angew.
Chem., Int. Ed. 2008, 47, 3787−3790. (b) Dohi, T.; Takenaga, N.;
Nakae, T.; Toyoda, Y.; Yamasaki, M.; Shiro, M.; Fujioka, H.;
Maruyama, A.; Kita, Y. J. Am. Chem. Soc. 2013, 135, 4558−4566.
(5) (a) Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem., Int. Ed.
2010, 49, 2175−2177. (b) Uyanik, M.; Yasui, T.; Ishihara, K.
Tetrahedron 2010, 66, 5841−5851. We also achieved the
enantioselective oxidative dearomatization of 1-naphthols using chiral
quaternary ammonium hypoiodite catalysis: Uyanik, M.; Sasakura, N.;
Kaneko, E.; Ohori, K.; Ishihara, K. Chem. Lett. 2015, 44, 179−181.
(6) (a) Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem., Int. Ed.
2013, 52, 9215−9218. (b) Uyanik, M.; Sasakura, N.; Mizuno, M.;
Ishihara, K. ACS Catal. 2017, 7, 872−876.
Crystal data for 9 (CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: ishihara@cc.nagoya-u.ac.jp.
■
ORCID
Muhammet Uyanik: 0000-0002-9751-1952
Kazuaki Ishihara: 0000-0003-4191-3845
Notes
(7) (a) Kurti, L.; Herczegh, P.; Visy, J.; Simonyi, M.; Antus, S.; Pelter,
̈
The authors declare no competing financial interest.
A. J. Chem. Soc., Perkin Trans. 1 1999, 379−380. (b) Pelter, A.; Ward,
R. S. Tetrahedron 2001, 57, 273−282.
ACKNOWLEDGMENTS
(8) (a) Xu, R.-Q.; Yang, P.; Tu, H.-F.; Wang, S.-G.; You, S.-L. Angew.
Chem., Int. Ed. 2016, 55, 15137−15141. (b) Xu, R.-Q.; Yang, P.; You,
S.-L. Chem. Commun. 2017, 53, 7553−7556. (c) Li, X.-Q.; Yang, H.;
Wang, J.-J.; Gou, B.-B.; Chen, J.; Zhou, L. Chem. - Eur. J. 2017, 23,
5381−5385.
■
Financial support for this project was partially provided by JSPS
KAKENHI (Grant Numbers 15H05755, 15H05484, 24245020,
and JP15H05810 in Precisely Designed Catalysts with
Customized Scaffolding), the Program for Leading Graduate
Schools: IGER Program in Green Natural Sciences (MEXT),
and a JSPS Research Fellowship for Young Scientists (T.Y.).
We thank Mr. Hiroki Okamoto for his assistance during the
initial screening of catalysts.
(9) (a) Rudolph, A.; Bos, P. H.; Meetsma, A.; Minnard, A. J.; Feringa,
B. L. Angew. Chem., Int. Ed. 2011, 50, 5834−5838. (b) Oguma, T.;
Katsuki, T. J. Am. Chem. Soc. 2012, 134, 20017. (c) Kim, C.; Oguma,
T.; Fujimoto, C.; Uchida, T.; Katsuki, T. Chem. Lett. 2016, 45, 1262−
1264.
(10) Nonenantioselective oxidative dearomatizative spirolactoniza-
tion of 2-naphthol derivatives has been reported: (a) Takenaga, N.;
Uchiyama, T.; Kato, D.; Fujioka, H.; Dohi, T.; Kita, Y. Heterocycles
2011, 82, 1327−1336. (b) Uyanik, M.; Nishioka, K.; Ishihara, K.
Heterocycles 2017, 95, 1132−1147.
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The Journal of Organic Chemistry
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DOI: 10.1021/acs.joc.7b01941
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