Nickel-catalyzed asymmetric ring opening of oxabenzonorbornadienes with arylboronic acids

Article abstract of DOI:10.1021/jo500821m

A new, versatile, and highly efficient nickel-catalyzed asymmetric ring-opening (ARO) reaction of oxabenzonorbornadienes with a wide variety of arylboronic acids has been developed, yielding cis-2-aryl-1,2-dihydronaphthalen- 1-ols in high yields (up to 99%) with good to excellent enantioselectivities (up to 99% ee) under very mild conditions. The effects of various nickel precursors, chiral bidentate ligands, catalyst loadings, bases, solvents, and temperatures on the yield and enantioselectivity of the reaction were also investigated. A plausible mechanism was proposed to account for the formation of the corresponding cis-ring-opened products based on the X-ray structure of product 4b.

Full text of DOI:10.1021/jo500821m

Article
pubs.acs.org/joc
Nickel-Catalyzed Asymmetric Ring Opening of
Oxabenzonorbornadienes with Arylboronic Acids
Zhongyi Zeng,† Dingqiao Yang,*,† Yuhua Long,*,† Xuejing Pan,† Guobao Huang,† Xiongjun Zuo,†
and Wen Zhou‡
†Guangzhou Key Laboratory of Materials for Energy Conversion and Storage; School of Chemistry and Environment, South China
Normal University, Guangzhou 510006, People’s Republic of China
‡Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, People’s Republic of China
S
* Supporting Information
ABSTRACT: A new, versatile, and highly efficient nickel-
catalyzed asymmetric ring-opening (ARO) reaction of
oxabenzonorbornadienes with a wide variety of arylboronic
acids has been developed, yielding cis-2-aryl-1,2-dihydronaph-
thalen-1-ols in high yields (up to 99%) with good to excellent
enantioselectivities (up to 99% ee) under very mild conditions.
The effects of various nickel precursors, chiral bidentate
ligands, catalyst loadings, bases, solvents, and temperatures on
the yield and enantioselectivity of the reaction were also
investigated. A plausible mechanism was proposed to account
for the formation of the corresponding cis-ring-opened products based on the X-ray structure of product 4b.
induction ability (up to 83% ee). Recently, our group
demonstrated a platinum-catalyzed ARO of oxabenzonorborna-
dienes with arylboronic acids, which generated cis-ring-opened
products in high yields (up to 97%) with good enantioselectiv-
ities (up to 89% ee).10 However, one common disadvantage for
these reported catalysts is that they are expensive, need a high
catalyst loading, and suffer poor compatibilities. Therefore,
development of a more versatile and efficient chiral catalyst for
this type of reaction is of great interest.
Nickel catalysts are particularly attractive by virtue of their
low price and high efficiency for the ARO of oxabicyclic alkenes
with DIBAL-H (diisobutyl aluminum hydride) and carboxylic
acids in excellent enantioselectivities of up to 99.5% ee.8 In
addition, Lautens et al. and Cheng et al. have reported nickel-
catalyzed ring-opening reactions of oxabicyclic alkenes using
organic halides, alkynes, Grignard reagents, and organo-
zirconium reagents, as important carbon nucleophiles.11
However, to the best of our knowledge, nickel-catalyzed
enantioselective ring opening of oxabicyclic alkenes by
arylboronic acids remains in demand. Herein, we report a
new, versatile, and highly efficient nickel-catalyzed ARO of
oxabenzonorbornadienes with arylboronic acids, which afford
cis-2-aryl-1,2-dihydronaphthalen-1-ols in high yields (up to
99%) with good to excellent enantioselectivities (up to 99%
ee). In particular, compared to the previous rhodium,
palladium, and platinum catalysts, this catalyst system features
a cheaper catalyst precursor, lower catalyst loading, and higher
INTRODUCTION
■
Transition-metal-catalyzed asymmetric ring-opening (ARO)
reactions of oxa- and azabicyclic alkenes have emerged as an
important method for the construction of carbon−carbon and
carbon−heteroatom bonds.1 These transformations are espe-
cially valuable because multiple stereocenters can be established
in a single step, and the resulting hydronaphthalene scaffolds
exist in a wide range of natural products and bioactive
molecules.2 Numerous metal catalysts, including rhodium,3
palladium,4 iridium,5 copper,6 zirconium,7 nickel,8 etc., have
been explored for the ARO of heterobicyclic alkenes with
hydride reagents as well as heteroatom and carbon
nucleophiles.
Among various carbon nucleophiles, arylboronic acids are
highly useful due to their commercial availability, structural
diversity, stability, and low toxicity. In 2002, Lautens and co-
workers reported the rhodium-catalyzed ARO addition of
arylboronic acids to [2.2.1]oxabicycle alkenes, in which high
yields and excellent enantioselectivities were obtained.3j
Meanwhile, Murakami et al. also described the rhodium-
catalyzed ring opening of oxabenzonorbornadienes with
arylboronic acids to obtain the corresponding racemic
products.9 In 2003, Lautens and co-workers successfully
extended the substrate scope of oxabenzonorbornadienes to
less-reactive aza-counterparts in the presence of a palladium
catalyst, affording cis-1-amino-2-aryldihydronaphthalenes in
excellent yields.4h In 2008, a chiral phosphine-containing
palladacycle catalyzed enantioselective arylative ring opening
of oxabenzonorbornadienes with arylboronic acids was
developed by Hou and co-workers.4i The reaction showed
high catalytic activity (up to 99% yield) and asymmetric
Received: April 12, 2014
Published: May 13, 2014
© 2014 American Chemical Society
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efficiency and enantioselectivity as well as better functional
group tolerance.
neutral and cationic Ni(II) salts were effective in catalyzing the
reaction (Table 1, entries 7−10). A slightly better result, a 95%
yield with 90% ee, was still achieved by Ni(cod)2. The catalyst
loading also had a significant effect on the yield of 2a. At 1 mol
% catalyst loading, 2a was formed cleanly (90% yield), whereas
neither an increase nor decrease in catalyst loading improved
the yield of the desired product (Table 1, entries 7, 11, and 12).
To further optimize reaction conditions, the impacts of
different parameters including solvents, bases, and temperatures
on the reactivity and enantioselectivity were subsequently
investigated (Table 2). An initial study of common solvents
RESULTS AND DISCUSSION
■
The substrates 1a−d were readily prepared by Diels−Alder
reactions of benzynes with furan according to literature
procedures.3c,12 To understand the nature of the catalytic
reaction and optimize the reaction conditions, we began our
investigation by treating oxabenzonorbornadiene 1a with
phenylboronic acid in CH2Cl2 at 25 °C in the presence of 1
mol % Ni(cod)2/DPPP as the catalyst, using KF as the
additive.10 The desired ring-opened product 2a was obtained in
25% yield after 7 h (Table 1, entry 1). Thereafter, a series of
a
Table 2. Optimization of Solvent, Base, and Temperature
Table 1. Effects of Nickel Precursor, Ligand, and Catalyst
a
Loading
b
entry
solvent
base
KF
temp (°C) time (h) yield (%) ee (%)
1
CH3CN
THF
25
25
25
25
25
25
25
25
25
25
25
25
25
0
24
24
22
3
n.r.
trace
20
−
−
2
KF
3
CH3OH
toluene
CH2Cl2
CHCl3
DCE
KF
85
88
90
89
89
88
84
89
−
4
KF
88
5
KF
3
92
6
KF
3
85
7
KF
1
95
8
DCE
Cs2CO3
K3PO4
KOH
Et3N
−
1
97
9
DCE
1
97
10
11
12
13
14
15
16
DCE
1
98
DCE
24
24
1
trace
trace
94
DCE
−
c
DCE
KOH
90
91
87
84
DCE
KOH
KOH
KOH
3
89
DCE
60
90
0.5
2
94
DCE
36
a
Ni precursor
(mol %)
time
(h)
yield
(%)
ee
Reaction conditions: Ni(cod)2 (1 mol %), (S,S)-Me-DuPhos (1 mol
%), 1a (0.3 mmol, 1 equiv), PhB(OH)2 (3 equiv), and base (5 M in
H2O, 0.5 equiv) reacted in the solvent of choice (2 mL) at the stated
b
entry
ligand
DPPP
(%)
1
2
3
4
Ni(cod)2 (1.0)
Ni(cod)2 (1.0)
Ni(cod)2 (1.0)
Ni(cod)2 (1.0)
7
25
60
49
n.r.
−
b
temperature. Determined by HPLC with a Chiralcel OD-H column.
(S)-DM-SegPhos
(S)-BINAP
7
70
79
−
c
Anhydrous KOH solid (0.5 equiv) was added.
7
(R)-(S)-PPF-
24
PtBu2
revealed a strong influence of the nature of solvent on
reactivity. The polar solvent CH3CN and ethereal solvent
tetrahydrofuran (THF) were totally ineffective (Table 2, entries
1−2). The protic solvent CH3OH afforded only a 20% yield
but satisfactory enantioselectivity (90% ee) (Table 2, entry 3).
Importantly, the reaction worked very well in the aromatic
solvent toluene and chlorinated solvents such as CHCl3,
CH2Cl2, and 1,2-dichloroethane (DCE) (Table 2, entries 4−7).
Among several solvents examined, DCE turn out to be the best,
providing product 2a in 95% yield with 89% ee. The impact of
bases was then surveyed to improve the efficiency of the
reaction as the base usually plays an important role in the
reaction involving arylboronic acids.13 KOH proved to be a
better base than KF, Cs2CO3, and K3PO4, providing the ring-
opening product in 95% yield and 89% ee after only 1 h (Table
2, entries 7−10). The reaction proceeded barely when the
organic weak base Et3N was used (Table 2, entry 11). As
expected, no reaction took place in the absence of any bases
(Table 2, entry 12). Interestingly, anhydrous KOH(s) caused no
deleterious effects, which suggested that the addition of water is
not essential in the present ARO reaction (Table 2, entry 13).
Temperature was also found to be crucial in this asymmetric
5
Ni(cod)2 (1.0)
Ni(cod)2 (1.0)
Ni(cod)2 (1.0)
(S)-PipPhos
24
24
3
n.r.
trace
95
−
−
6
(S,S)-Me-BPE
(S,S)-Me-DuPhos
7
90
84
88
87
89
89
8
Ni(dppe)Cl2 (1.0) (S,S)-Me-DuPhos
Ni(PPh3)2Cl2 (1.0) (S,S)-Me-DuPhos
Ni(PPh3)2Br2 (1.0) (S,S)-Me-DuPhos
7
90
9
3
89
10
11
12
3
90
Ni(cod)2 (0.5)
Ni(cod)2 (2.0)
(S,S)-Me-DuPhos
(S,S)-Me-DuPhos
5
80
4
79
a
Reaction conditions (unoptimized): 1a (0.3 mmol, 1 equiv),
PhB(OH)2 (3 equiv), and KF (5 M in H2O, 0.5 equiv) reacted in
CH2Cl2 (2 mL) at 25 °C, and the molar ratio of Ni precursor/ligand =
1:1. Determined by HPLC with a Chiralcel OD-H column.
b
chiral bidentate ligands were examined, among which (S,S)-Me-
DuPhos showed the best performance with regard to reactivity
and enantioselectivity (Table 1, entry 7). Other chiral bidentate
ligands including (S)-DM-SegPhos, (S)-BINAP, (S,S)-Me-BPE,
(R)-(S)-PPF-PtBu2, and (S)-PipPhos gave either inferior results
or no reaction (Table 1, entries 2−6). With (S,S)-Me-DuPhos
as the chiral ligand, the impact of several commercially available
nickel sources was also evaluated. It was observed that both
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transformation. The proper temperature was found to be 25 °C
(Table 2, entry 10). The reaction run at 0 °C gave a diminished
yield and slightly improved ee (Table 2, entry 14). Raising the
temperature to 60 °C somewhat decreased the yield and ee,
whereas a further increase to 90 °C resulted in only a 36%
conversion even after a prolonged reaction time (Table 2,
entries 15−16). Consequently, the optimum reaction con-
ditions were determined as follows: 1 mol % Ni(cod)2, 1 mol %
(S,S)-Me-DuPhos, 3 equiv of arylboronic acids, and 0.5 equiv of
KOH (5 M in H2O) in DCE at 25 °C.
Naphthylboronic acid proved to be a suitable nucleophile,
with moderate yield (56%) and good ee (89%) (Table 3, entry
11). Disubstituted arylboronic acids also showed remarkable
reactivity and good enantioselectivity (Table 3, entries 12, 13,
and 15−17). For instance, the reactions of 1a with 3,5-
dimethylphenyl and 3,4-(methylenedioxy)phenylboronic acids
gave products 2o and 2q in excellent yields (98% vs 99%) with
good ee (89% vs 92%), respectively (Table 3, entries 15 and
17). Unfortunately, owing to steric hindrance, 2,6-dimethyl-
phenylboronic acid failed to furnish the expected product 2n
(Table 3, entry 14).
Under the optimized reaction conditions, a series of mono-
and disubstituted arylboronic acids were examined to evaluate
their effect on the reactivity and enantioselectivity (Table 3). It
The substrate scope of oxabenzonorbornadiene derivatives
was further evaluated, and the results were compiled in Table 4.
Table 3. Nickel-Catalyzed ARO of Oxabenzonorbornadiene
1a with Various Arylboronic Acids
Table 4. Scope of Nickel-Catalyzed ARO of
a
Oxabenzonorbornadienes 1b−d with Various Arylboronic
a
Acids
b
entry
Ar
product time (h) yield (%) ee (%)
1
C6H5
2a
2b
2c
2d
2e
2f
1
98
90
56
99
40
80
91
63
44
84
56
97
98
n.r.
98
99
99
89
86
90
86
66
90
89
90
90
84
89
74
72
−
2
3-FC6H4
7
3
4-ClC6H4
5
4
3-ClC6H4
5
time
(h)
yield
(%)
ee
(%)
5
2-ClC6H4
24
20
5
b
entry substrate
Ar
product
6
4-F3CC6H4
1
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
C6H5
3a
3b
3c
3d
3e
3f
10
20
5
93
88
94
90
97
89
85
97
87
60
91
96
97
98
98
99
87
97
90
92
88
98
99
90
90
89
84
86
78
83
83
73
65
86
86
97
7
4-CH3C6H4
2g
2h
2i
2
3-FC6H4
8
3-CH3C6H4
5
3
3-ClC6H4
9
2-CH3C6H4
20
7
4
4-CH3C6H4
3-CH3C6H4
2,3-(CH3)2C6H3
3,5-(CH3)2C6H3
3-Cl-4-CH3C6H3
C6H5
20
5
10
11
12
13
14
15
16
17
4-CH3SC6H4
2-naphthyl
2j
5
2k
2l
6
6
20
20
20
7
2,3-(CH3)2C6H3
2,4-(CH3)2C6H3
2,6-(CH3)2C6H3
3,5-(CH3)2C6H3
3-Cl-4-CH3C6H3
3,4-OCH2OC6H3
5
7
3g
3h
4a
4b
4c
4d
4e
4f
2m
2n
2o
2p
2q
5
8
48
3
9
89
82
92
10
11
12
13
14
15
16
17
18
4-ClC6H4
20
6
5
3-ClC6H4
5
4-CH3C6H4
3-CH3C6H4
2,3-(CH3)2C6H3
2,4-(CH3)2C6H3
3,5-(CH3)2C6H3
3-Cl-4-CH3C6H3
5
a
Reaction conditions: Ni(cod)2 (1 mol %), (S,S)-Me-DuPhos (1 mol
%), 1a−d (0.3 mmol, 1 equiv), arylboronic acids (3 equiv), and KOH
(5 M in H2O, 0.5 equiv) reacted in DCE (2 mL) at 25 °C.
5
5
b
4g
4h
4i
5
Determined by HPLC with a Chiralcel OD-H column.
6
5
appeared that the electronic property of the substituents on the
phenyl ring in arylboronic acids had little effect on
enantioselectivities. Except for 2-chlorophenylboronic acid,
which gave product 2e in slightly lower enantioselectivity
(66% ee), other monosubstituted phenylboronic acids, with
electron-donating, electron-withdrawing, or neutral substitu-
ents, could react with oxabenzonorbornadiene 1a smoothly to
generate the corresponding ring-opening products in good
enantioselectivities (86−90% ee’s) (Table 3, entries 1−10).
However, the positional property of the substituents had a
significant impact on reactivity. In general, para- and meta-
substituted arylboronic acids gave better results than ortho-
substituent counterparts (Table 3, entries 3−5 and 7−9).
Moreover, it should be noteworthy that the treatment of 1a
with 2-methylboronic acid afforded product 2i in modest yield
(44%) but high enantioselectivity (90% ee), which dramatically
decreased to no more than 30% ee in analogous palladium- and
platinum-catalyzed reactions (Table 3, entry 9).4i,10 2-
3,4-
OCH2OC6H3
4j
5
19
1d
C6H5
5a
24
92
85
a
Reaction conditions: Ni(cod)2 (1 mol %), (S,S)-Me-DuPhos (1 mol
%), 1a−d (0.3 mmol, 1 equiv), arylboronic acids (3 equiv), and KOH
(5 M in H2O, 0.5 equiv) reacted in DCE (2 mL) at 25 °C.
Determined by HPLC with a Chiralcel OD-H or Chiralpak AD-H
column.
b
Besides 1a, the oxabenzonorbornadienes with different
substituents on the phenyl ring all reacted with various
arylboronic acids smoothly to generate the anticipated ring-
opening products in high yields (up to 99%) with good to
excellent enantioselectivities (up to 99%). Furthermore, the
nature of disubstituted groups in oxabenzonorbornadienes has
a substantial impact on the reactivity and enantioselectivity.
Electron-deficient substrate 1b displayed more reactive and
enantioselective than electron-rich substrate 1c (Table 4,
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entries 1−8 vs 9−18). For example, 6,7-dibromo-substituted 1b
reacted with phenylboronic acid to provide product 3a in 93%
yield with 90% ee, whereas 5,8-dimethoxy-substituted 1c with
phenylboronic acid afforded 4a in 87% yield with 84% ee
(Table 4, entries 1 and 9). The excellent performance of this
catalyst system is highlighted by the reaction of 1b with 3-
methylboronic acid, which furnished product 3e in excellent
yield (97%) with remarkable enantioselectivity (99% ee) (Table
4, entry 5). In addition, bulkier substrate 1d was also a viable
substrate for this reaction, providing the corresponding product
5a in 92% yield with 85% ee after 24 h (Table 4, entry 19).
The single crystal of ring-opened product 4b was obtained by
solvent evaporation from a mixture of petroleum ether, ethyl
acetate, and CH2Cl2. Its absolute configuration was assigned as
(1S,2R) and determined as a 1,2-cis-configuration by X-ray
crystallography, as shown in the Supporting Information.
Based on our observations and the known nickel chemistry,
the following key pathways in Scheme 1 were proposed to
enantioselectivities. Compared with the previous rhodium-,
palladium-, and platinum-catalyzed protocols, this nickel
catalyst system features a cheaper catalyst precursor, lower
catalyst loading, higher efficiency and enantioselectivity, and
better functional group tolerance. More detailed mechanistic
studies and the applications of this methodology in the
synthesis of bioactive molecules are currently underway in our
laboratory.
EXPERIMENTAL SECTION
■
General Procedure for Nickel-Catalyzed ARO Reactions of
Oxabenzonorbornadienes 1a−d with Arylboronic Acids. A 10.0
mL round-bottom flask was flame-dried under a stream of nitrogen
and cooled to room temperature. Ni(cod)2 (0.8 mg, 0.003 mmol, 1
mol %) and (S,S)-Me-DuPhos (0.9 mg, 0.003 mmol, 1 mol %) were
simultaneously added and followed by the addition of anhydrous DCE
(2 mL). After the mixture was stirred for about 30 min, to the system
were added substrates 1a−d (0.3 mmol), arylboronic acids (0.9
mmol), and KOH solution (5 M in H2O, 30 μL, 0.5 equiv)
sequentially. The reaction mixture was stirred at room temperature
until it was completed as judged by thin-layer chromatography. The
solvent was removed in vacuo, and the crude mixture was purified by
column chromatography on 200−300 mesh silica gels to afford target
products.
Scheme 1. Proposed Mechanism for Nickel(0)-Catalyzed
ARO of Oxabenzonorbornadiene 1a with Arylboronic Acids
(1S,2R)-2-Phenyl-1,2-dihydronaphthalen-1-ol (2a). Prepared ac-
cording to general procedure. Colorless oil (65.3 mg, 98% yield). Rf =
0.21 on silica gel (ethyl acetate/petroleum ether 1:10, v/v). The ee
was determined to be 89% using HPLC analysis on a chiralcel OD-H
column (hexane/2-propanol 90:10, 1.0 mL/min, λ = 254 nm).
25
Retention times were 7.4 (minor) and 11.3 min (major). [α]D
=
+160.4 (c 1.00, CHCl3). IR (neat film, cm−1): 3418(br), 3027(m),
1
2917(w), 1599(w), 1490(m), 1449(m), 1067(m), 765(s), 697(s). H
NMR (400 MHz, CDCl3): δ 7.35−7.23 (m, 8H), 7.17 (d, J = 7.2 Hz,
1H), 6.71 (dd, J = 9.6, 1.6 Hz, 1H), 6.13 (dd, J = 9.6, 3.9 Hz, 1H), 4.93
(t, J = 5.7 Hz, 1H), 3.88 (d, J = 5.6 Hz, 1H), 1.50 (d, J = 7.0 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 137.7, 135.9, 132.7, 129.7,
129.3, 128.7, 128.3, 128.2, 128.0, 127.4, 126.7, 126.4, 71.3, 47.3.
HRMS (APCI-ion trap) m/z: [M − 3H]− calcd for C16H11O,
219.0810; found 219.0809.
(1S,2R)-2-(3-Fluorophenyl)-1,2-dihydronaphthalen-1-ol (2b). Pre-
pared according to general procedure. Colorless oil (64.9 mg, 90%
yield). Rf = 0.22 on silica gel (ethyl acetate/petroleum ether 1:10, v/v).
The ee was determined to be 86% using HPLC analysis on a chiralcel
account for the formation of ring-opened products 2.8a,b,11a The
active chiral nickel(0) catalyst A was initially formed through
replacing one 1,5-cyclooctadiene (cod) ligand of the catalyst
precursor Ni(cod)2 by (S,S)-Me-DuPhos.14 Oxidative addition
of oxabenzonorbornadiene 1a with nickel(0) catalyst A occurs
to yield (π-allyl)nickel(II) complex B. Chelation of A with the
carbon−carbon double bond and oxygen atom of 1a may be
responsible for the high exo selectivity. This species then
undergoes transmetalation with ArB(OH)2 to form (alkenyl)-
(π-allyl)-nickel(II) intermediate C, which might require a base
to activate arylboronic acids and promote the catalytic cycle.9
Reductive elimination and further protonolysis with water or
arylboronic acids afford cis-ring-opened product 2 and
regenerate the nickel(0) species. It should be noted that, in
the present proposed mechanism, the oxidation state of nickel
changes from 0 to +2 and finally reduces back to 0.
OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ = 254 nm).
25
Retention times were 7.7 (minor) and 11.0 min (major). [α]D
=
+155.0 (c 1.00, CHCl3). IR (neat film, cm−1): 3424(br), 3048(w),
2924(s), 2866(w), 1663(w), 1595(s), 1489(s), 1450(s), 1238(m),
1
785(s), 708(w); H NMR (500 MHz, CDCl3): δ 7.33−7.23 (m, 4H),
7.17 (d, J = 7.3 Hz, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.98−6.93 (m, 2H),
6.70 (d, J = 9.6 Hz, 1H), 6.08 (dd, J = 9.6, 3.9 Hz, 1H), 4.90 (t, J = 5.3
Hz, 1H), 3.84 (s, 1H), 1.53 (d, J = 7.1 Hz, 1H). 13C{1H} NMR (125
1
3
MHz, CDCl3): δ 163.0 (d, JC−F = 243.8 Hz), 140.7 (d, JC−F = 7.5
Hz), 136.0, 132.4, 130.0 (d, 3JC−F = 7.5 Hz), 129.0, 128.6, 128.5, 128.2,
4
2
126.7, 126.6, 125.0 (d, JC−F = 2.5 Hz), 116.2 (d, JC−F = 21.3 Hz),
114.3 (d, 2JC−F = 21.3 Hz), 71.3, 47.1. 19F NMR (470 MHz, CDCl3): δ
−112.7 − −112.8 (m). HMRS (ESI-ion trap) m/z: [M + Na]+ calcd
for C16H13OFNa, 263.0848; found 263.0832.
(1S,2R)-2-(4-Chlorophenyl)-1,2-dihydronaphthalen-1-ol (2c). Pre-
pared according to general procedure. A white solid (43.1 mg, 56%
yield). Mp 59−60 °C. Rf = 0.22 on silica gel (ethyl acetate/petroleum
ether 1:10, v/v). The ee was determined to be 90% using HPLC
analysis on a chiralcel OD-H column (hexane/2-propanol 90:10, 1.0
mL/min, λ = 254 nm). Retention times were 6.8 (minor) and 10.2
CONCLUSIONS
■
25
min (major). [α]D = +127.1 (c 1.00, CHCl3). IR (neat film, cm−1):
In conclusion, we have developed a new, versatile, and highly
efficient nickel-catalyzed ARO reaction of oxabenzonorborna-
dienes with arylboronic acids under very mild conditions. It
provides a convenient and rapid entry to cis-2-aryl-1,2-
dihydronaphthalen-1-ols in high yields with good to excellent
3418(br), 3027(w), 2923(m), 2852(w), 1663(w), 1487(s), 1407(m),
1
1089(m), 840(m), 801(s), 765(m). H NMR (400 MHz, CDCl3): δ
7.32−7.16 (m, 8H), 6.70 (d, J = 9.6 Hz, 1H), 6.06 (dd, J = 9.5, 3.9 Hz,
1H), 4.89 (d, J = 5.1 Hz, 1H), 3.81 (s, 1H), 1.53 (s, 1H). 13C{1H}
NMR (100 MHz, CDCl3): δ 136.3, 135.9, 133.2, 132.4, 130.7, 129.2,
5252
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Article
128.7, 128.5, 128.4, 128.2, 126.6, 126.5, 71.2, 46.7. HRMS (ESI-ion
trap) m/z: [M + Cl]− calcd for C16H13OCl2, 291.0344; found
291.0345.
254 nm). Retention times were 5.8 (minor) and 7.6 min (major).
25
[α]D = +140.9 (c 1.00, CHCl3). IR (neat film, cm−1): 3434(br),
3027(m), 2918(m), 2854(w), 1665(w), 1604(m), 1480(m), 1451(m),
1070(m), 774(s), 708(m). 1H NMR (400 MHz, CDCl3): δ 7.35−7.16
(m, 5H), 7.10−7.05 (m, 3H), 6.70 (dd, J = 9.6, 2.0 Hz, 1H), 6.11 (dd,
J = 9.6, 3.9 Hz, 1H), 4.89 (t, J = 4.9 Hz, 1H), 3.85−3.82 (m, 1H), 2.33
(s, 3H), 1.53 (d, J = 6.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3):
δ 138.3, 137.8, 136.0, 132.6, 130.0, 129.7, 128.6, 128.4, 128.2, 128.1,
128.0, 126.9, 126.4, 126.1, 71.3, 47.3, 21.5. HRMS (ESI-ion trap) m/z:
[M + Na]+ calcd for C17H16ONa, 259.1099; found 259.1091.
(1S,2R)-2-(3-Chlorophenyl)-1,2-dihydronaphthalen-1-ol (2d).
Prepared according to general procedure. Pale yellow oil (76.2 mg,
99% yield). Rf = 0.26 on silica gel (ethyl acetate/petroleum ether 1:10,
v/v). The ee was determined to be 86% using HPLC analysis on a
chiralcel OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
254 nm). Retention times were 6.8 (minor) and 9.2 min (major).
25
[α]D = +108.7 (c 1.00, CHCl3). IR (neat film, cm−1): 3412(br),
3033(w), 2923(w), 2853(w), 1663(m), 1594(m), 1569(m), 1473(m),
1072(m), 782(s), 700(m). 1H NMR (400 MHz, CDCl3): δ 7.32−7.13
(m, 8H), 6.70 (d, J = 9.6 Hz, 1H), 6.05 (dd, J = 9.6, 3.6 Hz, 1H), 4.85
(d, J = 3.7 Hz, 1H), 3.80 (s, 1H), 1.59 (s, 1H). 13C{1H} NMR (100
MHz, CDCl3): δ 140.3, 135.8, 134.4, 132.3, 129.8, 129.5, 128.9, 128.6,
128.6, 128.2, 127.5, 127.4, 126.8, 126.6, 71.2, 47.1. HRMS (ESI-ion
trap) m/z: [M + Cl]− calcd for C16H13OCl2, 291.0344; found
291.0344.
(1S,2R)-2-(2-Methylphenyl)-1,2-dihydronaphthalen-1-ol (2i). Pre-
pared according to general procedure. Colorless oil (31.2 mg, 44%
yield). Rf = 0.29 on silica gel (ethyl acetate/petroleum ether 1:10, v/v).
The ee was determined to be 90% using HPLC analysis on a chiralcel
OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ = 254 nm).
Retention times were 5.9 (minor) and 8.9 min (major). [α]D25 = +65.2
(c 1.00, CHCl3). IR (neat film, cm−1): 3412(br), 3027(m), 2923(m),
2852(w), 1665(w), 1599(w), 1484(m), 1454(m), 1070(m), 763(s),
744(s). 1H NMR (400 MHz, CDCl3): δ 7.34−7.15 (m, 8H), 6.70 (dd,
J = 9.6, 2.4 Hz, 1H), 6.06 (dd, J = 9.6, 3.2 Hz, 1H), 4.80 (t, J = 5.8 Hz,
1H), 4.19−4.16 (m, 1H), 2.42 (s, 3H), 1.54 (d, J = 6.3 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 136.8, 136.6, 135.4, 132.5,
(1S,2R)-2-(2-Chlorophenyl)-1,2-dihydronaphthalen-1-ol (2e). Pre-
pared according to a general procedure. A white solid (30.8 mg, 40%
yield). Mp 130−131 °C. Rf = 0.23 on silica gel (ethyl acetate/
petroleum ether 1:10, v/v). The ee was determined to be 66% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
90:10, 1.0 mL/min, λ = 254 nm). Retention times were 7.2 (minor)
and 12.1 min (major). [α]D25 = +24.3 (c 1.00, CHCl3). IR (neat film,
cm−1): 3302(br), 3044(w), 2918(w), 2852(w), 1591(m), 1427(m),
130.7, 130.5, 129.3, 128.7, 128.0, 127.9, 127.7, 127.3, 126.6, 126.4,
69.6, 43.2, 19.9. HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for
C17H16ONa, 259.1099; found: 259.1090.
(1S,2R)-2-[4-(Methylthio)phenyl]-1,2-dihydronaphthalen-1-ol
(2j). Prepared according to general procedure. Colorless oil (67.6 mg,
84% yield). Rf = 0.18 on silica gel (ethyl acetate/petroleum ether 1:10,
v/v). The ee was determined to be 84% using HPLC analysis on a
chiralcel OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
254 nm). Retention times were 9.8 (minor) and 16.0 min (major).
1
1353(s), 1119(m), 1012(m), 818(m), 755(m). H NMR (400 MHz,
CDCl3): δ 7.44−7.19 (m, 8H), 6.74 (dd, J = 9.6 Hz, 2.4 Hz, 1H), 6.04
(dd, J = 9.6, 1.8 Hz, 1H), 4.89 (d, J = 3.7 Hz, 1H), 4.50−4.47 (m, 1H),
1.57 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 136.9, 135.1,
134.2, 132.1, 131.0, 129.6, 129.1, 128.8, 128.5, 128.3, 128.1, 128.0,
127.0, 126.7, 69.2, 44.0. HRMS (ESI-ion trap) m/z: [M + Cl]− calcd
for C16H13OCl2, 291.0344; found 291.0345.
25
[α]D = +328.5 (c 1.00, CHCl3). IR (neat film, cm−1): 3360(br),
3196(w), 2918(s), 2853(m), 1742(m), 1634(m), 1462(m), 1414(m),
1
1240(s), 1051(m), 883(w), 801(w). H NMR (500 MHz, CDCl3): δ
(1S,2R)-2-(4-Trifluoromethylphenyl)-1,2-dihydronaphthalen-1-ol
(2f). Prepared according to general procedure. A white solid (69.7 mg,
80% yield). Mp 72−73 °C. Rf = 0.26 on silica gel (ethyl acetate/
petroleum ether 1:10, v/v). The ee was determined to be 90% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
90:10, 1.0 mL/min, λ = 254 nm). Retention times were 6.5 (minor)
and 10.3 min (major). [α]D25 = +120.3 (c 1.00, CHCl3). IR (neat film,
cm−1): 3363(br), 3037(w), 2923 (w), 2852(w), 1619(w), 1416(w),
7.33 (d, J = 7.2 Hz, 1H), 7.30−7.23 (m, 2H), 7.20−7.15 (m, 5H), 6.69
(d, J = 9.6 Hz, 1H), 6.09 (dd, J = 9.5, 3.9 Hz, 1H), 4.92 (t, J = 6.4 Hz,
1H), 3.81 (s, 1H), 2.45 (s, 3H), 1.48 (d, J = 7.1 Hz, 1H). 13C{1H}
NMR (125 MHz, CDCl3): δ 137.5, 136.2, 134.4, 132.6, 129.8, 129.6,
128.3, 128.1, 126.9, 126.6, 126.4, 71.3, 46.8, 15.9. HRMS (ESI-ion
trap) m/z: [M + Na]+ calcd for C17H16OSNa, 291.0820; found
291.0802.
(1S,2R)-1,2-Dihydro-[2,2′-binaphthalen]-1-ol (2k). Prepared ac-
cording to general procedure. Colorless oil (43.6 mg, 56% yield). Rf =
0.27 on silica gel (ethyl acetate/petroleum ether 1:10, v/v). The ee
was determined to be 89% using HPLC analysis on a chiralcel OD-H
1
1325 (s), 1163(m), 1122(m), 1067(m), 807(m), 768(w). H NMR
(400 MHz, CDCl3): δ 7.55 (d, J = 7.7 Hz, 2H), 7.38−7.17 (m, 6H),
6.73 (d, J = 9.6 Hz, 1H), 6.08 (dd, J = 9.5, 4.0 Hz, 1H), 4.89 (s, 1H),
3.89 (s, 1H), 1.59 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): 142.5,
2
135.8, 132.4, 129.7, 129.5 (q, JC−F = 24.0 Hz), 128.8, 128.7, 128.6,
column (hexane/2-propanol 90:10, 1.0 mL/min, λ = 254 nm).
128.3, 126.7, 126.6, 124.2 (q, 1JC−F = 270.3 Hz), 125.4 (q, 3JC−F = 3.7
Hz), 71.3, 47.3. 19F NMR (376 MHz, CDCl3): δ − 62.5. HRMS (ESI-
ion trap) m/z: [M + Na]+ calcd for C17H13OF3Na, 313.0816; found
313.0807.
25
Retention times were 10.3 (minor) and 12.8 min (major). [α]D
=
+152.4 (c 1.00, CHCl3). IR (neat film, cm−1): 3407(br), 3049(m),
2918(m), 2852(w), 1660(m), 1597(m), 1506(w), 1377(w), 1077(m),
1
807(s), 746(s). H NMR (400 MHz, CDCl3): δ 7.80−7.34 (m, 4H),
(1S,2R)-2-(4-Methylphenyl)-1,2-dihydronaphthalen-1-ol (2g).
Prepared according to general procedure. Colorless oil (64.5 mg,
91% yield). Rf = 0.33 on silica gel (ethyl acetate/petroleum ether 1:10,
v/v). The ee was determined to be 89% using HPLC analysis on a
chiralcel OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
254 nm). Retention times were 5.8 (minor) and 8.1 min (major).
7.47−7.42 (m, 2H), 7.34−7.18 (m, 5H), 6.75 (dd, J = 9.6, 1.9 Hz,
1H), 6.20 (dd, J = 9.6, 4.0 Hz, 1H), 4.98 (s, 1H), 4.02−3.99 (m, 1H),
1.55 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 136.2, 135.4,
133.5, 132.8, 132.7, 129.6, 128.5, 128.4, 128.3, 128.1, 127.8, 127.6,
127.3, 126.8, 126.5, 126.2, 125.9, 71.3, 47.5. HRMS (ESI-ion trap) m/
z: [M + Na]+ calcd for C20H16ONa, 295.1099; found 295.1089.
(1S,2R)-2-(2,3-Dimethylphenyl)-1,2-dihydronaphthalen-1-ol (2l).
Prepared according to general procedure. Colorless oil (72.8 mg, 97%
yield). Rf = 0.22 on silica gel (ethyl acetate/petroleum ether 1:10, v/v).
The ee was determined to be 74% using HPLC analysis on a chiralcel
OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ = 254 nm).
Retention times were 6.7 (minor) and 9.3 min (major). [α]D25 = +67.2
(c 1.00, CHCl3). IR (neat film, cm−1): 3431(br), 3026(m), 2928(m),
2866(w), 1661(w), 1589(w), 1464(m), 1379(m), 1069(m), 827(m),
25
[α]D = +170.5 (c 1.00, CHCl3). IR (neat film, cm−1): 3429(br),
3027(m), 2918(m), 2858(w), 1663(w), 1512(m), 1451(m), 1070(m),
1
790(s). H NMR (400 MHz, CDCl3): δ 7.34−7.22 (m, 3H), 7.17−
7.10 (m, 5H), 6.68 (dd, J = 9.6, 1.8 Hz, 1H), 6.11 (dd, J = 9.6, 4.1 Hz,
1H), 4.91 (d, J = 5.2 Hz, 1H), 3.84−3.81 (m, 1H), 2.31 (s, 3H), 1.53
(s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 137.1, 136.2, 134.4,
132.7, 129.9, 129.4, 129.1, 128.2, 128.1, 128.0, 126.7, 126.3, 71.3, 46.9,
21.1. HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for C17H16ONa,
259.1099; found 259.1090.
1
775(s). H NMR (500 MHz, CDCl3): δ 7.35−7.23 (m, 3H), 7.19−
(1S,2R)-2-(3-Methylphenyl)-1,2-dihydronaphthalen-1-ol (2h).
Prepared according to general procedure. Colorless oil (44.7 mg,
63% yield). Rf = 0.34 on silica gel (ethyl acetate/petroleum ether 1:10,
v/v). The ee was determined to be 90% using HPLC analysis on a
chiralcel OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
7.16 (m, 2H), 7.11−7.06 (m, 2H), 6.71 (dd, J = 9.6, 2.5 Hz, 1H), 6.07
(dd, J = 9.6, 2.9 Hz, 1H), 4.78 (t, J = 5.0 Hz, 1H), 4.28 (dt, J = 5.4, 2.8
Hz, 1H), 2.33 (d, J = 4.8 Hz, 6H), 1.50 (d, J = 5.6 Hz, 1H). 13C{1H}
NMR (125 MHz, CDCl3): δ 137.3, 136.6, 135.4, 135.2, 132.5, 130.8,
129.1, 128.7, 127.9, 127.8, 127.7, 127.2, 126.6, 125.8, 69.8, 43.5, 21.1,
5253
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15.2. HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for C18H18ONa,
273.1255; found 273.1240.
The ee was determined to be 90% using HPLC analysis on a chiralcel
OD-H column (hexane/2-propanol 95:5, 1.0 mL/min, λ = 254 nm).
25
(1S,2R)-2-(2,4-Dimethylphenyl)-1,2-dihydronaphthalen-1-ol
(2m). Prepared according to general procedure. Colorless oil (73.6 mg,
98% yield). Rf = 0.24 on silica gel (ethyl acetate/petroleum ether 1:10,
v/v). The ee was determined to be 72% using HPLC analysis on a
chiralcel OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
254 nm). Retention times were 6.0 (minor) and 9.4 min (major).
Retention times were 12.3 (minor) and 16.4 min (major). [α]D
=
+142.7 (c 1.00, CHCl3). IR (neat film, cm−1): 3374(br), 3033(w),
2918(m), 2852(w), 1660(w), 1580(w), 1468(m), 1380(w), 1070(m),
1
1013(w), 886(m), 760(m), 700(s). H NMR (400 MHz, CDCl3): δ
7.57 (s, 1H), 7.40 (s, 1H), 7.29 (s, 3H), 7.17 (d, J = 5.5 Hz, 2H), 6.59
(d, J = 9.6 Hz, 1H), 6.20 (dd, J = 9.2, 4.4 Hz, 1H), 4.96 (d, J = 5.5 Hz,
1H), 3.82 (s, 1H), 1.57 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ
137.1, 135.6, 133.5, 131.8, 131.5, 130.8, 129.3, 128.9, 127.9, 126.4,
124.0, 123.6, 70.3, 46.7. HRMS (ESI-ion trap) m/z: [M − 3H]− calcd
for C16H9OBr2, 376.9000; found 376.9013.
25
[α]D = +108.2 (c 1.00, CHCl3). IR (neat film, cm−1): 3422(br),
3030(m), 2922(s), 2853(w), 1668(w), 1503(m), 1452(m), 1377(m),
1074(m), 800(s), 764(m). 1H NMR (500 MHz, CDCl3): δ 7.36−7.24
(m, 3H), 7.17 (dd, J = 14.1, 7.6 Hz, 2H), 7.06 (s, 1H), 6.98 (d, J = 7.8
Hz, 1H), 6.71 (d, J = 9.6 Hz, 1H), 6.07 (dd, J = 9.6, 2.9 Hz, 1H), 4.82
(t, J = 4.9 Hz, 1H), 4.17 (d, J = 2.4 Hz, 1H), 2.41 (s, 3H), 2.31 (s,
3H), 1.55 (d, J = 5.6 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ
136.9, 136.5, 135.6, 133.5, 132.6, 131.6, 130.7, 129.2, 128.6, 127.9,
127.8, 127.6, 127.1, 126.5, 69.8, 42.9, 21.0, 19.8. HRMS (ESI-ion trap)
m/z: [M + Na]+ calcd for C18H18ONa, 273.1255; found 273.1241.
(1S,2R)-2-(3,5-Dimethylphenyl)-1,2-dihydronaphthalen-1-ol (2o).
Prepared according to general procedure. Colorless oil (73.6 mg, 98%
yield). Rf = 0.37 on silica gel (ethyl acetate/petroleum ether 1:10, v/v).
The ee was determined to be 89% using HPLC analysis on a chiralcel
(1S,2R)-6,7-Dibromo-2-(3-fluorophenyl)-1,2-dihydronaphthalen-
1-ol (3b). Prepared according to general procedure. Colorless oil
(105.1 mg, 88% yield). Rf = 0.14 on silica gel (ethyl acetate/petroleum
ether 1:15, v/v). The ee was determined to be 92% using HPLC
analysis on a chiralcel OD-H column (hexane/2-propanol 95:5, 1.0
mL/min, λ = 254 nm). Retention times were 12.5 (minor) and 15.4
25
min (major). [α]D = +203.8 (c 1.00, CHCl3). IR (neat film, cm−1):
3412(br), 3046(w), 2928(s), 2847(w), 1665(w), 1584(m), 1483(s),
1
1449(m), 1242(m), 1080(s), 891(s), 783(s), 702(m). H NMR (500
MHz, CDCl3): δ 7.58 (s, 1H), 7.41 (s, 1H), 7.28−7.25 (m, 1H), 6.99−
6.95 (m, 2H), 6.90−6.87 (m, 1H), 6.61 (dd, J = 9.6, 1.6 Hz, 1H), 6.17
(dd, J = 9.7, 4.7 Hz, 1H), 4.94 (s, 1H), 3.81 (ddd, J = 6.4, 4.7, 1.6 Hz,
1H), 1.57 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ 163.0 (d,
OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ = 254 nm).
25
Retention times were 5.0 (minor) and 6.3 min (major). [α]D
=
+139.7 (c 1.00, CHCl3). IR (neat film, cm−1): 3434(br), 3022(m),
2918(s), 2857(w), 1663(w), 1602(s), 1482(m), 1454(m), 1377(m),
1075(m), 851(m), 806(s), 787(s), 760(m). 1H NMR (400 MHz,
CDCl3): δ 7.24−7.21 (m, 3H), 7.16 (d, J = 7.2 Hz, 1H), 6.90 (s, 3H),
6.68 (d, J = 9.6 Hz, 1H), 6.10 (dd, J = 9.4, 2.8 Hz, 1H), 4.84 (s, 1H),
3.80 (d, J = 1.3 Hz, 1H), 2.28 (s, 6H), 1.55 (s, 1H). 13C{1H} NMR
(100 MHz, CDCl3): δ 138.3, 137.9, 136.0, 132.7, 129.8, 129.1, 128.4,
128.1, 127.9, 127.1, 126.9, 126.4, 71.3, 47.3, 21.4. HRMS (ESI-ion
trap) m/z: [M + Na]+ calcd for C18H18ONa, 273.1255; found
273.1239.
3
1JC−F = 246.3 Hz), 138.7 (d, JC−F = 6.3 Hz), 136.8, 133.2, 131.5,
3
4
131.1, 131.0, 130.3 (d, JC−F = 7.5 Hz), 126.8, 125.0 (d, JC−F = 2.5
2
2
Hz), 124.3, 123.9, 116.2 (d, JC−F = 21.3 Hz), 114.8 (d, JC−F = 20
Hz), 70.2, 46.5. 19F NMR (470 MHz, CDCl3): δ −112.1 − −112.2
(m). HRMS (ESI-ion trap) m/z: [M − H]− calcd for C16H10OFBr2,
394.9082; found 394.9082.
(1S,2R)-6,7-Dibromo-2-(3-chlorophenyl)-1,2-dihydronaphthalen-
1-ol (3c). Prepared according to general procedure. Colorless oil
(116.9 mg, 94% yield). Rf = 0.26 on silica gel (ethyl acetate/petroleum
ether 1:10, v/v). The ee was determined to be 88% using HPLC
analysis on a chiralcel OD-H column (hexane/2-propanol 95:5, 1.0
mL/min, λ = 254 nm). Retention times were 13.5 (minor) and 15.6
(1S,2R)-2-(3-Chloro-4-methylphenyl)-1,2-dihydronaphthalen-1-
ol (2p). Prepared according to a general procedure. Colorless oil (80.4
mg, 99% yield). Rf = 0.30 on silica gel (ethyl acetate/petroleum ether
1:10, v/v). The ee was determined to be 82% using HPLC analysis on
a chiralcel OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
254 nm). Retention times were 7.0 (minor) and 9.7 min (major).
25
min (major). [α]D = +235.8 (c 1.00, CHCl3). IR (neat film, cm−1):
3408(br), 3030(w), 2922(s), 2857(w), 1665(w), 1595(m), 1476(s),
1
1430(m), 1250(m), 1072(s), 885(s), 785(s), 700(m). H NMR (500
25
[α]D = +253.5 (c 1.00, CHCl3). IR (neat film, cm−1): 3424(br),
MHz, CDCl3): δ 7.57 (s, 1H), 7.41 (s, 1H), 7.25−7.20 (m, 3H), 7.06
(d, J = 7.3 Hz, 1H), 6.61 (d, J = 9.6 Hz, 1H), 6.15 (dd, J = 9.6, 4.4 Hz,
1H), 4.92 (t, J = 7.0 Hz, 1H), 3.79 (t, J = 5.2 Hz, 1H), 1.58 (d, J = 6.1
Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ 138.4, 136.7, 134.6,
133.2, 131.6, 131.1, 130.9, 130.0, 129.5, 128.0, 127.4, 126.8, 124.4,
123.8, 70.2, 46.5. HRMS (ESI-ion trap) m/z: [M − 3H]− calcd for
C16H8OClBr2, 410.8610; found 410.8611.
3028(m), 2905(s), 2847(w), 1730(m), 1663(w), 1566(w), 1483(s),
1441(m), 1248(m), 1055(s), 997(m), 795 (s), 760(m). 1H NMR (500
MHz, CDCl3): δ 7.33−7.23 (m, 4H), 7.17−7.14 (m, 2H), 7.04 (d, J =
7.8 Hz, 1H), 6.70 (d, J = 9.6 Hz, 1H), 6.06 (dd, J = 9.6, 3.9 Hz, 1H),
4.88 (t, J = 6.4 Hz, 1H), 3.79 (s, 1H), 2.33 (s, 3H), 1.50 (d, J = 7.7 Hz,
1H). 13C{1H} NMR (125 MHz, CDCl3): δ 137.3, 136.0, 135.1, 134.5,
132.5, 131.1, 129.8, 129.1, 128.5, 128.2, 127.4, 126.7, 126.5, 71.3, 46.7,
19.7. HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for C17H15OClNa,
293.0709; found 293.0691.
(1S,2R)-6,7-Dibromo-2-(4-methylphenyl)-1,2-dihydronaph-
thalen-1-ol (3d). Prepared according to general procedure. Pale
yellow oil (106.4 mg, 90% yield). Rf = 0.19 on silica gel (ethyl acetate/
petroleum ether 1:20, v/v). The ee was determined to be 98% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol 95:5,
1.0 mL/min, λ = 254 nm). Retention times were 9.3 (minor) and 11.1
(1S,2R)-2-(Benzo[d][1,3]dioxol-5-yl)-1,2-dihydronaphthalen-1-ol
(2q). Prepared according to general procedure. Pale yellow oil (79.1
mg, 99% yield). Rf = 0.14 on silica gel (ethyl acetate/petroleum ether
1:10, v/v). The ee was determined to be 92% using HPLC analysis on
a chiralcel OD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
254 nm). Retention times were 12.1 (minor) and 16.3 min (major).
25
min (major). [α]D = +119.3 (c 1.00, CHCl3). IR (neat film, cm−1):
3412(br), 3016(m), 2918(s), 2851(w), 1665(w), 1575(w), 1509 (s),
1465(s), 1377(m), 1276(m), 1108(s), 1075(s), 1018(m), 889(s),
25
[α]D = +247.5 (c 1.00, CHCl3). IR (neat film, cm−1): 3366(br),
1
848(s), 779(m), 683(w). H NMR (400 MHz, CDCl3): δ 7.57 (s,
3028(w), 2905(m), 2837(w), 1743(m), 1634(w), 1483(s), 1445(m),
1H), 7.39 (s, 1H), 7.07 (dd, J = 23.9, 7.7 Hz, 4H), 6.57 (d, J = 9.6 Hz,
1H), 6.18 (dd, J = 9.5, 4.8 Hz, 1H), 4.95 (d, J = 2.3 Hz, 1H), 3.78 (t, J
= 5.6 Hz, 1H), 2.30 (s, 3H), 1.55 (s, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 137.7, 137.3, 133.6, 132.2, 132.0, 131.4, 130.7, 129.6, 129.2,
126.2, 123.9, 123.5, 70.2, 46.3, 21.0. HRMS (ESI-ion trap) m/z: [M −
3H]− calcd for C17H11OBr2, 390.9156; found 390.9151.
1
1248(s), 1045(s), 939(m), 795 (s), 760(m). H NMR (500 MHz,
CDCl3): δ 7.35 (d, J = 7.1 Hz, 1H), 7.29−7.22 (m, 2H), 7.15−7.14
(m, 1H), 6.75−6.72 (m, 2H), 6.70 (s, 1H), 6.66 (dd, J = 9.6, 1.7 Hz,
1H), 6.07 (dd, J = 9.6, 4.3 Hz, 1H), 5.90−5.89 (m, 2H), 4.90 (t, J = 6.7
Hz, 1H), 3.77 (ddd, J = 6.2, 4.3, 1.9 Hz, 1H), 1.57 (s, 1H). 13C{1H}
NMR (125 MHz, CDCl3): δ 147.9, 147.0, 136.2, 132.6, 131.1, 129.8,
128.3, 128.2, 128.1, 126.5, 126.4, 122.5, 109.6, 108.4, 101.0, 71.3, 46.9.
HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for C17H14O3Na,
289.0841; found 289.0820.
(1S,2R)-6,7-Dibromo-2-(3-methylphenyl)-1,2-dihydronaph-
thalen-1-ol (3e). Prepared according to general procedure. Colorless
oil (114.7 mg, 97% yield). Rf = 0.33 on silica gel (ethyl acetate/
petroleum ether 1:15, v/v). The ee was determined to be 99% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
90:10, 1.0 mL/min, λ = 254 nm). Retention times were 5.1 (minor)
(1S,2R)-6,7-Dibromo-2-phenyl-1,2-dihydronaphthalen-1-ol (3a).
Prepared according to general procedure. Colorless oil (106.0 mg, 93%
yield). Rf = 0.19 on silica gel (ethyl acetate/petroleum ether 1:20, v/v).
25
and 6.9 min (major). [α]D = +133.1 (c 1.00, CHCl3). IR (neat film,
5254
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The Journal of Organic Chemistry
Article
cm−1): 3407(br), 3033(m), 2918(m), 2852(w), 1602(w), 1465(m),
1377 (w), 1108(m), 1072(m), 1020(w), 886(s), 776(s), 705(m). H
7.08 (m, 1H), 6.80 (q, J = 8.9 Hz, 2H), 6.14 (d, J = 9.8 Hz, 1H), 5.09
(s, 1H), 3.81−3.80 (m, 7H), 1.63 (s, 1H). 13C{1H} NMR (100 MHz,
CDCl3): δ 150.7, 149.6, 140.4, 129.1, 128.9, 128.6, 127.0, 124.2, 122.5,
122.1, 111.4, 110.9, 64.3, 56.2, 56.1, 47.3. HRMS (ESI-ion trap) m/z:
[M + Na]+ calcd for C18H18O3Na, 305.1154; found 305.1144.
1
NMR (400 MHz, CDCl3): δ 7.57 (s, 1H), 7.39 (s, 1H), 7.17 (t, J = 7.5
Hz, 1H), 7.08 (d, J = 7.4 Hz, 1H), 7.00 (s, 1H), 6.95 (d, J = 7.5 Hz,
1H), 6.58 (d, J = 9.6 Hz, 1H), 6.18 (dd, J = 9.6, 4.6 Hz, 1H), 4.91 (d, J
= 5.7 Hz, 1H), 3.78 (t, J = 5.0 Hz, 1H), 2.31 (s, 3H), 1.58 (s, 1H).
13C{1H} NMR (100 MHz, CDCl3): δ 138.6, 137.1, 135.7, 133.5,
131.8, 131.6, 130.8, 130.1, 128.8, 128.7, 126.3, 126.1, 124.0, 123.5,
70.2, 46.7, 21.5. HRMS (ESI-ion trap) m/z: [M − 3H]− calcd for
C17H11OBr2, 390.9156; found 390.9148.
(1S,2R)-5,8-Dimethoxy-2-(4-chlorophenyl)-1,2-dihydronaph-
thalen-1-ol (4b). Prepared according to general procedure. A white
solid (57.0 mg, 60% yield). Mp 97−98 °C. Rf = 0.18 on silica gel (ethyl
acetate/petroleum ether 1:5, v/v). The ee was determined to be 86%
using HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 12.7 (minor)
and 18.8 min (major). [α]D25 = −33.2 (c 1.00, CHCl3). IR (neat film,
cm−1): 3462(br), 3040(w), 2928(m), 2843(m), 1589(w), 1481(s),
(1S,2R)-6,7-Dibromo-2-(2,3-dimethylphenyl)-1,2-dihydronaph-
thalen-1-ol (3f). Prepared according to general procedure. Colorless
oil (109.0 mg, 89% yield). Rf = 0.22 on silica gel (ethyl acetate/
petroleum ether 1:20, v/v). The ee was determined to be 90% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol 99:1,
1.0 mL/min, λ = 254 nm). Retention times were 18.2 (minor) and
1
1260(s), 1084(s), 799(s), 718(m). H NMR (400 MHz, CDCl3): δ
7.34 (s, 4H), 7.08 (d, J = 9.7 Hz, 1H), 6.80 (q, J = 9.0 Hz, 2H), 6.05
(d, J = 9.7 Hz, 1H), 5.05 (s, 1H), 3.81 (d, J = 7.6 Hz, 6H), 3.73 (s,
1H), 1.66 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 150.6, 149.6,
139.1, 132.7, 130.6, 128.6, 128.4, 124.2, 122.3, 122.2, 111.4, 111.0,
64.3, 56.2, 56.1, 46.6. HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for
C18H17O3ClNa, 339.0764; found 339.0752.
25
19.7 min (major). [α]D = +168.2 (c 1.00, CHCl3). IR (neat film,
cm−1): 3431(br), 3036(w), 2922(s), 2857(w), 1601(m), 1464(s),
1
1375(m), 1246(m), 1074(m), 887(m), 779(m), 710(m). H NMR
(500 MHz, CDCl3): δ 7.60 (s, 1H), 7.43 (s, 1H), 7.11 (d, J = 5.1 Hz,
1H), 7.07−7.00 (m, 2H), 6.60 (d, J = 9.6 Hz, 1H), 6.15 (dd, J = 9.6,
3.7 Hz, 1H), 4.84 (t, J = 6.1 Hz, 1H), 4.27 (dd, J = 5.5, 2.4 Hz, 1H),
2.33 (d, J = 5.5 Hz, 6H), 1.55 (d, J = 6.9 Hz, 1H). 13C{1H} NMR (125
MHz, CDCl3): δ 137.6, 136.4, 135.4, 134.8, 133.4, 132.8, 132.5, 131.0,
129.5, 126.9, 126.0, 125.9, 124.4, 123.3, 69.0, 42.7, 21.2, 15.4. HRMS
(ESI-ion trap) m/z: [M − H]− calcd for C18H15OBr2, 404.9490; found
404.9489.
(1S,2R)-5,8-Dimethoxy-2-(3-chlorophenyl)-1,2-dihydronaph-
thalen-1-ol (4c). Prepared according to general procedure. Colorless
oil (86.5 mg, 91% yield). Rf = 0.24 on silica gel (ethyl acetate/
petroleum ether 1:5, v/v). The ee was determined to be 78% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 12.2 (minor)
and 17.7 min (major). [α]D25 = +192.8 (c 1.00, CHCl3). IR (neat film,
cm−1): 3426(br), 3055(w), 2932(m), 2837(w), 1593(m), 1485(s),
(1S,2R)-6,7-Dibromo-2-(3,5-dimethylphenyl)-1,2-dihydronaph-
thalen-1-ol (3g). Prepared according to general procedure. Colorless
oil (104.1 mg, 85% yield). Rf = 0.23 on silica gel (ethyl acetate/
petroleum ether 1:20, v/v). The ee was determined to be 90% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol 98:2,
1.0 mL/min, λ = 254 nm). Retention times were 14.4 (minor) and
1
1258(s), 1090(s), 957(m), 783(m), 731(m). H NMR (500 MHz,
CDCl3): δ 7.36−7.18 (m, 5H), 7.09 (dd, J = 9.8, 2.6 Hz, 1H), 6.84−
6.79 (m, 1H), 6.07 (d, J = 9.8 Hz, 1H), 5.08 (d, J = 3.7 Hz, 1H), 3.82
(d, J = 5.9 Hz, 6H), 3.75 (s, 1H), 1.62 (s, 1H). 13C{1H} NMR (125
MHz, CDCl3): δ 150.6, 149.7, 142.8, 134.1, 129.7, 129.4, 128.8, 128.1,
127.6, 127.4, 127.1, 122.4, 111.6, 111.1, 64.3, 56.3, 56.2, 47.1. HRMS
(ESI-ion trap) m/z: [M + Na]+ calcd for C18H17O3ClNa, 339.0764;
found 339.0743.
25
17.2 min (major). [α]D = +198.6 (c 1.00, CHCl3). IR (neat film,
cm−1): 3408(br), 3040(w), 2928(s), 2857(w), 1668(m), 1582(w),
1446(s), 1385(m), 1246(m), 1080(m), 887(s), 777(s). 1H NMR (500
MHz, CDCl3): δ 7.59 (s, 1H), 7.40 (s, 1H), 6.92 (s, 1H), 6.80 (s, 2H),
6.58 (d, J = 9.7 Hz, 1H), 6.17 (dd, J = 9.6, 4.4 Hz, 1H), 4.89 (t, J = 7.2
Hz, 1H), 3.76 (t, J = 5.3 Hz, 1H), 2.27 (s, 6H), 1.55 (d, J = 7.3 Hz,
1H). 13C{1H} NMR (125 MHz, CDCl3): δ 138.6, 137.1, 135.7, 133.5,
131.8, 131.7, 130.9, 129.6, 127.0, 126.2, 124.1, 123.4, 70.2, 46.7, 21.4.
HRMS (ESI-ion trap) m/z: [M − H]− calcd for C18H15OBr2,
404.9490; found 404.9489.
(1S,2R)-5,8-Dimethoxy-2-(4-methylphenyl)-1,2-dihydronaph-
thalen-1-ol (4d). Prepared according to general procedure. Colorless
oil (85.4 mg, 96% yield). Rf = 0.21 on silica gel (ethyl acetate/
petroleum ether 1:5, v/v). The ee was determined to be 83% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 14.5 (minor)
and 23.7 min (major). [α]D25 = −20.2 (c 1.00, CHCl3). IR (neat film,
cm−1): 3549(br), 3049(w), 2932(m), 2843(m), 1599(m), 1514(m),
(1S,2R)-6,7-Dibromo-2-(3-chloro-4-methylphenyl)-1,2-dihydro-
naphthalen-1-ol (3h). Prepared according to general procedure. Pale
yellow oil (124.7 mg, 97% yield). Rf = 0.28 on silica gel (ethyl acetate/
petroleum ether 1:10, v/v). The ee was determined to be 89% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol 95:5,
1.0 mL/min, λ = 254 nm). Retention times were 10.7 (minor) and
1
1483(s), 1258(s), 1086(s), 959(m), 793(s), 714(m). H NMR (400
MHz, CDCl3): δ 7.31 (d, J = 7.7 Hz, 2H), 7.20 (d, J = 7.7 Hz, 2H),
7.08 (dd, J = 9.8, 3.0 Hz, 1H), 6.80 (q, J = 8.9 Hz, 2H), 6.12 (d, J = 9.8
Hz, 1H), 5.06 (s, 1H), 3.81 (d, J = 4.4 Hz, 6H), 3.75 (s, 1H), 2.36 (s,
3H), 1.61 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 150.7, 149.6,
137.2, 136.6, 129.3, 129.2, 129.0, 124.3, 122.6, 122.0, 111.4, 110.9,
64.4, 56.2, 56.1, 46.8, 21.1. HRMS (ESI-ion trap) m/z: [M + Na]+
calcd for C19H20O3Na, 319.1310; found 319.1300.
25
11.9 min (major). [α]D = +197.9 (c 1.00, CHCl3). IR (neat film,
cm−1): 3393(br), 3036(w), 2928(s), 2847(m), 1665(m), 1489(m),
1
1466(m), 1393(m), 1209(m), 1080(m), 891(s), 799(m), 708(m). H
NMR (500 MHz, CDCl3): δ 7.57 (s, 1H), 7.40 (s, 1H), 7.17 (s, 1H),
7.13 (d, J = 7.7 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 6.59 (d, J = 9.7 Hz,
1H), 6.14 (dd, J = 9.6, 4.6 Hz, 1H), 4.90 (t, J = 7.1 Hz, 1H), 3.75 (t, J
= 5.4 Hz, 1H), 2.32 (s, 3H), 1.60 (d, J = 8.2 Hz, 1H). 13C{1H} NMR
(125 MHz, CDCl3): δ 136.9, 135.6, 135.2, 134.7, 133.3, 131.5, 131.3,
131.2, 131.0, 129.9, 127.4, 126.7, 124.2, 123.8, 70.2, 46.1, 19.7. HRMS
(ESI-ion trap) m/z: [M − H]− calcd for C17H12OClBr2, 424.8943;
found 424.8940.
(1S,2R)-5,8-Dimethoxy-2-(3-methylphenyl)-1,2-dihydronaph-
thalen-1-ol (4e). Prepared according to general procedure. Colorless
oil (86.2 mg, 97% yield). Rf = 0.28 on silica gel (ethyl acetate/
petroleum ether 1:5, v/v). The ee was determined to be 83% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 9.9 (minor)
and 13.6 min (major). [α]D25 = −41.7 (c 1.00, CHCl3). IR (neat film,
cm−1): 3449(br), 3003(w), 2938(m), 2837(w), 1601(m), 1483(s),
1331(m), 1257(s), 1008(s), 959(m), 775(m), 712(m). 1H NMR (400
MHz, CDCl3): δ 7.31−7.23 (m, 3H), 7.14−7.08 (m, 2H), 6.82 (q, J =
8.9 Hz, 2H), 6.15 (d, J = 9.8 Hz, 1H), 5.08 (s, 1H), 3.83 (d, J = 2.9 Hz,
6H), 3.77 (s, 1H), 2.39 (s, 3H), 1.58 (s, 1H). 13C{1H} NMR (100
MHz, CDCl3): δ 150.7, 149.6, 140.2, 138.2, 129.8, 129.0, 128.5, 127.8,
126.1, 124.2, 122.6, 122.0, 111.4, 110.8, 64.3, 56.3, 56.2, 47.2, 21.5.
HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for C19H20O3Na,
319.1310; found 319.1295.
(1S,2R)-5,8-Dimethoxy-2-phenyl-1,2-dihydronaphthalen-1-ol
(4a). Prepared according to general procedure. Colorless oil (73.7 mg,
87% yield). Rf = 0.23 on silica gel (ethyl acetate/petroleum ether 1:5,
v/v). The ee was determined to be 84% using HPLC analysis on a
chiralcel OD-H column (hexane/2-propanol 85:15, 1.0 mL/min, λ =
254 nm). Retention times were 11.1 (minor) and 16.7 min (major).
25
[α]D = −46.9 (c 1.00, CHCl3). IR (neat film, cm−1): 3421(br),
3030(w), 2941(m), 2833(m), 1601(m), 1483(s), 1441(s), 1344(s),
1
1258(s), 1090(s), 957(m), 799(m), 758(m), 698(s). H NMR (400
(1S,2R)-5,8-Dimethoxy-2-(2,3-dimethylphenyl)-1,2-dihydronaph-
thalen-1-ol (4f). Prepared according to general procedure. Colorless
MHz, CDCl3): δ 7.43−7.37 (m, 4H), 7.30 (t, J = 6.3 Hz, 1H), 7.11−
5255
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oil (91.3 mg, 98% yield). Rf = 0.25 on silica gel (ethyl acetate/
petroleum ether 1:5, v/v). The ee was determined to be 73% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 10.8 (minor)
and 14.3 min (major). [α]D25 = −33.3 (c 1.00, CHCl3). IR (neat film,
cm−1): 3366(br), 3046(w), 2922(m), 2853(w), 1633(w), 1481(s),
1375(m), 1258(s), 1086(m), 957(w), 777(m), 714(m). 1H NMR
(500 MHz, CDCl3): δ 7.29 (d, J = 7.4 Hz, 1H), 7.15−7.07 (m, 3H),
6.84−6.78 (m, 2H), 6.11 (d, J = 11.3 Hz, 1H), 5.09 (s, 1H), 4.12 (dd, J
= 5.7, 3.9 Hz, 1H), 3.82 (d, J = 7.1 Hz, 6H), 2.33 (s, 3H), 2.31 (s, 3H),
1.51 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ 151.0, 149.7,
138.0, 137.2, 134.8, 130.5, 128.9, 127.6, 125.6, 124.1, 122.7, 121.5,
111.5, 110.9, 62.1, 56.4, 56.3, 43.6, 21.1, 15.1. HRMS (ESI-ion trap)
m/z: [M + Na]+ calcd for C20H22O3Na, 333.1467; found 333.1444.
(1S,2R)-5,8-Dimethoxy-2-(2,4-dimethylphenyl)-1,2-dihydronaph-
thalen-1-ol (4g). Prepared according to general procedure. Colorless
oil (91.3 mg, 98% yield). Rf = 0.25 on silica gel (ethyl acetate/
petroleum ether 1:5, v/v). The ee was determined to be 65% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 9.2 (minor)
and 14.2 min (major). [α]D25 = −25.9 (c 1.00, CHCl3). IR (neat film,
cm−1): 3445(br), 3003(w), 2932(s), 2837(w), 1607(m), 1485(s),
NMR (500 MHz, CDCl3): δ 7.06 (dd, J = 9.8, 3.2 Hz, 1H), 6.92 (d, J
= 1.7 Hz, 1H), 6.88 (dd, J = 7.9, 1.7 Hz, 1H), 6.83−6.81 (m, 2H), 6.78
(d, J = 9.0 Hz, 1H), 6.07−6.04 (m, 1H), 5.95−5.94 (m, 2H), 5.03 (s,
1H), 3.81 (d, J = 3.0 Hz, 6H), 3.71−3.69 (m, 1H), 1.64 (s, 1H).
13C{1H} NMR (125 MHz, CDCl3): δ 150.8, 149.7, 147.8, 146.6,
134.3, 129.1, 124.4, 122.5, 122.1, 122.0, 111.5, 111.0, 109.7, 108.3,
101.0, 64.5, 56.3, 56.2, 47.0. HRMS (ESI-ion trap) m/z: [M + Na]+
calcd for C19H18O5Na, 349.1052; found 349.1028.
(1S,2R)-2-Phenyl-1,2-dihydrotriphenylen-1-ol (5a). Prepared ac-
cording to general procedure. A yellow solid (88.9 mg, 92% yield). Mp
129−130 °C. Rf = 0.19 on silica gel (ethyl acetate/petroleum ether
1:10, v/v). The ee was determined to be 85% using HPLC analysis on
a chiralpak AD-H column (hexane/2-propanol 90:10, 1.0 mL/min, λ =
254 nm). Retention times were 49.2 (minor) and 53.3 min (major).
25
[α]D = −150.2 (c 1.00, CHCl3). IR (neat film, cm−1): 3407(br),
3022(w), 2923(m), 2856(w), 1645(w), 1495(m), 1449(m), 1397(w),
1072(m), 751 (s), 740(s). 1H NMR (400 MHz, CDCl3): δ 8.73 (t, J =
7.6 Hz, 2H), 8.27 (dd, J = 23.9, 5.3 Hz, 2H), 7.68−7.44 (m, 9H), 7.38
(d, J = 6.5 Hz, 1H), 6.46 (d, J = 9.7 Hz, 1H), 5.41 (s, 1H), 4.01 (s,
1H), 1.68 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ 140.1, 130.8,
130.7, 130.6, 129.9, 129.2, 128.8, 128.7, 128.6, 127.3, 127.2, 126.9,
126.8, 126.5, 126.4, 124.1, 123.9, 123.8, 123.1, 123.0, 67.6, 48.0.
HRMS (ESI-ion trap) m/z: [M + Na]+ calcd for C24H18ONa,
345.1255; found 345.1242.
1
1335(m), 1258(s), 1088(s), 957(m), 800(s), 714(m). H NMR (500
MHz, CDCl3): δ 7.30 (d, J = 7.6 Hz, 1H), 7.10−7.05 (m, 3H), 6.82−
6.77 (m, 2H), 6.08 (d, J = 10.0 Hz, 1H), 5.07 (s, 1H), 4.00 (d, J = 1.6
Hz, 1H), 3.81 (d, J = 6.9 Hz, 6H), 2.36 (s, 3H), 2.32 (s, 3H), 1.55 (s,
1H). 13C{1H} NMR (125 MHz, CDCl3): δ 151.0, 149.7, 137.5, 136.6,
135.1, 131.4, 130.4, 129.7, 126.9, 124.2, 122.7, 121.7, 111.5, 111.0,
61.9, 56.33, 56.31, 43.0, 21.0, 19.6. HRMS (ESI-ion trap) m/z: [M +
Na]+ calcd for C20H22O3Na, 333.1467; found 333.1446.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures; copies of H and 13C{1H} NMR
1
spectra of compounds 2a−m, 2o−q, 3a−h, 4a−j, and 5a; 19F
NMR spectra of compounds 2b, 2f, and 3b; HPLC conditions
and spectra of compounds 2a−d, 2f−k, 2o−q, 3b−f, 3h, 4a,
4d−e, 4h−j, and 5a; and X-ray crystal data for compound 4b in
CIF format. This material is available free of charge via the
Internet at http://pubs.acs.org.
(1S,2R)-5,8-Dimethoxy-2-(3,5-dimethylphenyl)-1,2-dihydronaph-
thalen-1-ol (4h). Prepared according to general procedure. Pale
yellow oil (92.2 mg, 99% yield). Rf = 0.24 on silica gel (ethyl acetate/
petroleum ether 1:5, v/v). The ee was determined to be 86% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 9.6 (minor)
and 12.0 min (major). [α]D25 = +18.7 (c 1.00, CHCl3). IR (neat film,
cm−1): 3455(br), 3007(w), 2928(m), 2847(w), 1661(w), 1603(m),
AUTHOR INFORMATION
Corresponding Authors
*E-mail: yangdq@scnu.edu.cn (D.Y.).
*E-mail: longyh@scnu.edu.cn (Y.L.).
■
1
1481(s), 1337(w), 1258(s), 1088(s), 858(w), 808(m), 714(m). H
NMR (500 MHz, CDCl3): δ 7.09−7.05 (m, 3H), 6.94 (s, 1H), 6.81−
6.78 (m, 2H), 6.14 (d, J = 9.8 Hz, 1H), 5.07 (s, 1H), 3.81 (s, 6H), 3.73
(s, 1H), 2.34 (s, 6H), 1.57 (s, 1H). 13C{1H} NMR (125 MHz,
CDCl3): δ 150.9, 149.7, 140.2, 138.2, 129.1, 128.8, 127.5, 126.9, 122.7,
122.0, 111.5, 111.0, 64.3, 56.3, 56.2, 47.1, 21.4. HRMS (ESI-ion trap)
m/z: [M + Na]+ calcd for C20H22O3Na, 333.1467; found 333.1448.
(1S,2R)-5,8-Dimethoxy-2-(3-chloro-4-methylphenyl)-1,2-dihydro-
naphthalen-1-ol (4i). Prepared according to general procedure.
Colorless oil (86.3 mg, 87% yield). Rf = 0.17 on silica gel (ethyl
acetate/petroleum ether 1:5, v/v). The ee was determined to be 86%
using HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 10.8 (minor)
and 17.1 min (major). [α]D25 = +44.3 (c 1.00, CHCl3). IR (neat film,
cm−1): 3360(br), 3003(w), 2918(m), 2847(w), 1659(w), 1596(w),
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully thank the National Natural Science Foundation
of China (21172081, 21372090), the Natural Science
Foundation of Guangdong Province (S2013020013091),
Produce, Learning and Research Project Program of Education
Department of Guangdong Province (2011A090200039), and
Guangzhou Pearl River New Star Plan of Science and
Technology Program (2012J2200015) for financial support
and also the Scientific Research Foundation of Graduate School
of South China Normal University (2013kyjj045) for support.
1
1485(s), 1260(s), 1088(s), 957(m), 808(m), 712(m). H NMR (500
MHz, CDCl3): δ 7.41 (s, 1H), 7.25−7.22 (m, 2H), 7.08 (dd, J = 9.8,
3.1 Hz, 1H), 6.83−6.78 (m, 2H), 6.07 (d, J = 9.8 Hz, 1H), 5.06 (s,
1H), 3.82 (d, J = 5.1 Hz, 6H), 3.72 (dd, J = 5.8, 3.6 Hz, 1H), 2.38 (s,
3H), 1.60 (s, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ 150.7, 149.7,
139.9, 134.6, 134.4, 130.9, 129.7, 128.4, 127.4, 124.4, 122.4, 122.3,
111.5, 111.1, 64.3, 56.3, 56.2, 46.6, 19.7. HRMS (ESI-ion trap) m/z:
[M + Na]+ calcd for C19H19O3ClNa, 353.0920; found 353.0900.
(1S,2R)-5,8-Dimethoxy-2-(benzo[d][1,3]dioxol-5-yl)-1,2-dihydro-
naphthalen-1-ol (4j). Prepared according to general procedure. Pale
yellow oil (95.0 mg, 97% yield). Rf = 0.27 on silica gel (ethyl acetate/
petroleum ether 1:3, v/v). The ee was determined to be 97% using
HPLC analysis on a chiralcel OD-H column (hexane/2-propanol
85:15, 1.0 mL/min, λ = 254 nm). Retention times were 17.2 (minor)
and 23.7 min (major). [α]D25 = +110.8 (c 1.00, CHCl3). IR (neat film,
cm−1): 3366(br), 3007(w), 2922 (m), 2843(w), 1599(w), 1483(s),
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