Iridium-catalyzed asymmetric ring-opening of oxabenzonorbornadienes with phenols

Article abstract of DOI:10.1021/jo3018507

A novel iridium-catalyzed asymmetric ring-opening (ARO) reaction of oxabenzonorbornadienes with a variety of phenols was reported, which afforded the corresponding trans-2-phenoxy-1,2-dihydronaphthalen-1-ol products in high yields with moderate to excellent enantioselectivities (up to 98% ee) under mild conditions. The trans products are formed via the enantioselective cleavage of a bridgehead carbon-oxygen bond in 1 followed by S_N2 nucleophilic attack by phenols. The effects of various bisphosphine ligands, Ag (I) salts, ammonium halides, bases, and solvents on the yield and enantioselectivity of the reaction were also investigated. The trans-configuration of the product 2a was confirmed by X-ray crystal structure analysis. A possible mechanism for the present catalytic reaction was proposed.

Full text of DOI:10.1021/jo3018507

Article
pubs.acs.org/joc
Iridium-Catalyzed Asymmetric Ring-Opening of
Oxabenzonorbornadienes with Phenols
Hanchao Cheng and Dingqiao Yang*
Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education, School of Chemistry and Environment, South
China Normal University, Guangzhou 510006, People’s Republic of China
S
* Supporting Information
ABSTRACT: A novel iridium-catalyzed asymmetric ring-
opening (ARO) reaction of oxabenzonorbornadienes with a
variety of phenols was reported, which afforded the
corresponding trans-2-phenoxy-1,2-dihydronaphthalen-1-ol
products in high yields with moderate to excellent
enantioselectivities (up to 98% ee) under mild conditions.
The trans products are formed via the enantioselective
cleavage of a bridgehead carbon−oxygen bond in 1 followed
by SN2 nucleophilic attack by phenols. The effects of various
bisphosphine ligands, Ag (I) salts, ammonium halides, bases,
and solvents on the yield and enantioselectivity of the reaction
were also investigated. The trans-configuration of the product
2a was confirmed by X-ray crystal structure analysis. A possible mechanism for the present catalytic reaction was proposed.
alkenes with phenols have rarely been investigated. Our interest
in generating carbon−oxygen bonds has prompted us to
expand the scope of the reaction to include phenol-induced
ring-openings of oxabicyclic alkenes for an efficient access to
trans-2-phenoxy-1,2-dihydronaphthalen-1-ols with regio-, dia-
stereo-, and enantioselectivities. Ring-opening carbon−oxygen
bond formation with oxabenzonorbornadiene 1 is a valuable
synthetic methodology to create highly functionalized ring
systems. These methods offer potentially useful routes to the
synthesis of enantioenriched trans-2-phenoxy-1,2-dihydronaph-
thalen-1-ols, which are the scaffolds for total synthesis of
bioactive compounds.21 Herein we report the full details of the
catalytic ARO reaction of oxabenzonorbornadienes with
phenols in the presence of iridium catalysts. The reactions
afford the corresponding trans-2-phenoxy-1,2-dihydronaphtha-
len-1-ols in moderate to good yields with excellent
enantioselectivities (up to 98% ee) under relatively mild
conditions.
INTRODUCTION
■
Transition-metal-catalyzed asymmetric ring-opening (ARO)
reactions of oxa- and azabicyclic alkenes have been demon-
strated to be useful methods for the synthesis of chiral building
blocks.1 Metal-catalyzed transformations that can establish the
absolute configuration with more than one stereocenter are
particularly attractive to synthetic chemists. The ARO reactions
of oxa- and azabicyclic alkenes with various carbon- and
heteroatom nucleophiles represent a type of organic reaction
for the efficient formation of asymmetric carbon−carbon and
carbon-heteroatom bonds, affording a variety of the ring-
opened products.2 This area has received increasing attention
and has been extensively investigated. Many parameters have
been examined for these reactions, including a variety of metal
catalysts such as Fe,3 Ni,4 Cu,5 Ru,6 Rh,7 Pd,8 etc., and
nucleophiles such as alcohols,9 phenols,7c,10 thiophenols,11
amines,7d,g,h,12 Grignard reagents,3,13 organozinc reagent-
s,8a,c−e,j,14 organoboronic acids,8l,n,15 organic halides,4a,8f,i
alkynes,4b,6b,16 and others.5b,d,17 Recently, Lautens and co-
workers reported the Rh-catalyzed ARO of oxabicyclic alkenes
with water.18 Those reactions provided potential promising
methods to form carbon−oxygen bonds through the addition
of oxygen-based nucleophiles to the oxabicyclic alkenes,
offering facile and efficient synthetic routes to optically active
compounds bearing multiple stereocenters. In addition,
oxabicyclic alkenes are valuable synthetic intermediates, as
they can serve as a general template to create highly substituted
ring systems.
RESULTS AND DISCUSSION
■
The substrates 1a−d were readily prepared by the Diels−Alder
reactions of benzynes with furan according to literature
procedures.7e,22 To explore the ring-opening reactions, an
achiral ligand 1,1′-bis(diphenylphosphino)ferrocene (DPPF)
was first chosen to validate the catalytic activity of the iridium
complex in the ring-opening reactions of oxabenzonorborna-
diene 1a with 4-chlorophenol in tetrahydrofuran (THF) at 80
°C (not shown in Table 1); unfortunately, we did not obtain
Very recently, we have reported the iridium-catalyzed ARO
reaction of oxa- and azabicyclic alkenes with amines and
phenols.19,20 However, the ARO reactions of oxabicyclic
Received: September 3, 2012
Published: October 8, 2012
© 2012 American Chemical Society
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the halide effect on the ring-opening reactions,7a,e,12 Bu4NI was
added as additive to the reaction mixture, and the
corresponding ring-opened product 2a was obtained in 31%
yield with 79% ee (Table 1, entry 9). Several bases were added
to the reaction mixture, but the results were not satisfactory
(Table 1, entries 10−12). The reaction seemed to proceed
smoothly when 1 equiv of Bu4NI and 5 equiv of a base were
added to the mixture (Table 1, entries 13−15). It was further
discovered that when using Bu4NI and N,N,N′,N′-tetramethy-
lethylenediamine (TMEDA) as additives, the reaction provided
the expected ring-opened product 2a in moderate yield with
excellent enantioselectivity (94% ee) (Table 1, entry 14). These
results showed that Bu4NI and TMEDA as additives were
highly effective for promoting the ring-opening of 2a. On the
other hand, the choice of ligand was very important. To
determine if there was a more suitable ligand for the
asymmetric reaction, a variety of achiral and chiral ligands
were evaluated (Table 1). Several chiral ligands such as (S)-
BINAP, (S)-p-Tol-BINAP, (R)-(S)-PPF-PtBu2, (S)-Segphos,
and (S)-PipPhos were then examined. Indeed, not all ligands
showed the same type or level of reactivity. Table 1 presents the
excellent performance of (S)-p-Tol-BINAP with regard to
catalytic activity and stereoselectivity when the molar ratio of
(S)-p-Tol-BINAP to iridium was 2:1 (Table 1, entries 11−15).
Other ligands such as (S)-BINAP, (R)-(S)-PPF-PtBu2, (S)-
Segphos, and (S)-PipPhos gave either unsatisfactory results
(Table 1, entries 4−6) or no reaction (Table 1, entry 7).
Therefore, we decided to choose (S)-p-Tol-BINAP as the
ligand for the reactions.
a
Table 1. Effect of Ligands and Additives
b
time
(h)
yield
(%)
ee
entry
ligand
additive
(%)
c
1
DPPP
72
48
12
12
48
10
15
30
20
17
0
c
2
(S)-p-Tol-BINAP
(S)-p-Tol-BINAP
(S)-BINAP
30
69
51
32
3
4
5
(R)-(S)-PPF-
PtBu2
6
(S)-Segphos
(S)-PipPhos
12
48
48
12
48
48
12
2
18
22
7
n.r.
trace
31
d
To obtain better yield and enantioselectivity, we then
investigated the impact of catalyst loading on the reaction
(Table 2, entries 1−5). The yield and enantioselectivity of 2a
8
(S)-p-Tol-BINAP NH4I
(S)-p-Tol-BINAP Bu4NI
d
9
79
e
f
10
11
12
(S)-p-Tol-BINAP Cs2CO3
(S)-p-Tol-BINAP Cs2CO3
trace
31
71
41
81
94
a
e
Table 2. Effect of the Catalyst Loading
(S)-p-Tol-BINAP Et3N
25
g
13
(S)-p-Tol-BINAP Bu4NI/Et3N
50
g
14
(S)-p-Tol-BINAP Bu4NI/
2
60
h
TMEDA
g
i
15
(S)-p-Tol-BINAP Bu4NI/PMP
2
61
92
a
Conditions: [Ir(cod)Cl]2 (2.5 mol %), ligand (5 mol %), AgOTf (10
b
mol %), Bu4NI (20 mol %), 1a (0.2 mmol), and 4-chlorophenol (1
entry
[Ir(cod)Cl]2 (mol %)
time (h)
yield (%)
ee (%)
b
mmol) reacted in THP at 80 °C (oil bath temperature). Determined
1
2
3
4
5
0.5
1
72
1
47
83
82
68
60
92
98
95
96
94
c
by HPLC with a Chiralcel AD-H column. Without addition of AgOTf
d
e
and Bu4NI. Ammonium halide (1 equiv) was added. Base (5 equiv)
f
1.5
2.0
2.5
1
was added. Cs2CO3 (5 equiv, 5 M in H2O) was added.
Tetrabutylammonium iodide (1 equiv) and a base (5 equiv) were
added. N,N,N′,N′-Tetramethylethylenediamine (TMEDA).
1,2,2,6,6-Pentamethylpiperidine (PMP).
g
1
h
2
i
a
Conditions: the reaction was carried out with 1a (0.2 mmol) and 4-
chlorophenol (1 mmol) in the presence of halide additive Bu4NI (0.2
mmol) and TMEDA (1 mmol) in THP at 80 °C (oil bath
temperature), and the ratio of [Ir(cod)Cl]2/(S)-p-Tol-BINAP/
AgOTf/Bu4NI = 1:2:4:8. Determined by HPLC with a Chiralcel
AD-H column.
the desired ring-opened product 2a. Another achiral ligand 1,3-
bis(diphenylphosphino)propane (DPPP) was tested without
additives and resulted in poor yield (10%) (Table 1, entry 1)
after 72 h. The results encouraged us to optimize the catalytic
reaction conditions, the desired ring-opened product 2a was
obtained in a 15% yield with 30% ee in the presence of 2.5 mol
% [Ir(cod)Cl]2 and 5 mol % (S)-p-Tol-BINAP (Table 1, entry
2). The yield was increased to 31% (Table 1, entry 9) when
silver(I) triflate (AgOTf) and ammonium halides as additives
were employed in the presence of [Ir(cod)Cl]2. Silver chloride
was first precipitated by the addition of AgOTf, which was
followed by the addition of the (S)-p-Tol-BINAP ligand and
then the addition of tetrabutylammonium iodide (Bu4NI). In
this way, by a halide-exchange protocol, cationic iridium
complexes [Ir((S)-p-Tol-BINAP)I]2 are formed. Considering
b
were strongly influenced by the catalyst loading. By allowing
the reaction to run for three days, the catalyst loading could be
lowered to 0.25 mol % (Table 2, entry 1). It would be a more
suitable catalyst loading in terms of the yield and ee when the
molar ratio of [Ir(cod)Cl]2 to (S)-p-Tol-BINAP was 1:2 (Table
2, entry 2). However, a further increase in catalyst loading for
the reaction did not improve the yield and ee (Table 2, entries
3−5).
To optimize the present reaction conditions, the effects of
different reaction parameters including the selection of solvents
and the reaction temperatures on reactivity and enantioselec-
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tivity were next investigated (as shown in Table 3). First of all
the effect of the solvent was investigated. It proved to have a
Table 4. Ir-Catalyzed ARO of Oxabenzonorbornadiene 1a
with Various Phenols
a
a
Table 3. Optimization of the Solvent and Temperature
b
entry
R
product time (h) yield (%) ee (%)
1
4-Cl
2a
2b
2c
2d
2e
2f
1
83
85
75
70
74
77
75
65
60
80
96
86
21
90
84
86
80
n.r.
98
76
95
46
93
77
66
75
94
98
90
77
43
60
73
94
75
b
2
3-Cl
1
entry
solvent
temperature (°C) time (h) yield (%) ee (%)
3
2-Cl
1
1
2
CH3CN
DCE
80
80
80
80
80
80
100
80
60
20
72
72
72
2
n.r.
trace
18
4
4-NO2
H
1.5
2
5
3
toluene
DME
87
99
95
94
93
98
93
6
4-CH3
3-CH3
2-CH3
2
4
57
7
2g
2h
2i
2
5
1,4-dioxane
THF
2
65
8
2
6
2
63
9
4-OCH3
2
7
THP
0.5
1
54
10
11
12
13
14
15
16
17
18
2,3-dichloro
2j
1
8
THP
83
2,4-dichloro
2k
2l
1
9
THP
3
82
2,5-dichloro
1
10
THP
72
n.r.
2,6-dichloro
2m
2n
2o
2p
2q
2r
48
1
a
Conditions (unoptimized): [Ir(cod)Cl]2 (1 mol %), ligand (2 mol
%), AgOTf (4 mol %), Bu4NI (8 mol %), 1a (0.2 mmol), halide
additive Bu4NI (0.2 mmol), TMEDA (1 mmol), and 4-chlorophenol
(1 mmol) reacted in the solvent of choice at the corresponding
4-chloro-3-methyl
2-bromo-4-chloro
4-bromo-2-chloro
2,4-dibromo
1
1
b
1
temperature. Determined by HPLC with a Chiralcel AD-H column.
2,6-di-tert-butyl
72
a
dramatic effect on the enantioselectivity of the reaction. When
the reaction was carried out in CH3CN and 1,2-dichloroethane
(DCE), respectively, we did not obtain any product 2a (Table
3, entries 1 and 2), while the employment of toluene resulted in
only 18% conversion after 72 h (Table 3, entry 3). The use of
1,2-dimethoxyethane (DME) resulted in moderate yield (57%)
with excellent ee (up to 99% ee) (Table 3, entry 4). Similar
results were obtained with 1,4-dioxane and THF (Table 3,
entries 5 and 6). The solvent was then changed from THF to
tetrahedropyran (THP), and a dramatic effect was observed on
the enantioselectivity, as it increased to 98% ee (Table 3, entry
8). Solvent effect study showed that THP was the best one
among the solvents tested. The effects of the temperature were
then investigated in the ring-opening reaction. By increasing the
oil bath temperature to 80 °C and running the reaction in THP,
the yield of 2a was increased to 83% with 98% ee (Table 3,
entry 8). Further increase of the temperature to 100 °C
resulted in 54% yield with 93% ee (Table 3, entry 7), although
only 0.5 h was required for full conversion. Unexpectedly,
lowering the temperature to 20 °C resulted in no reaction
(Table 3, entry 10). Therefore, optimum reaction temperature
was identified as 80 °C in THP, giving the desired product 2a
in good yield (83%) with excellent enantioselectivity (98% ee)
(Table 3, entry 8).
The single crystal of the product 2a was obtained by solvent
evaporation from a solution consisting of petroleum ether,
ethanol, and ethyl acetate. Its absolute configuration was
assigned as (1S,2S) and confirmed as 1,2-trans-configuration by
X-ray crystal structure analysis, as shown in the Supporting
Information.
With the optimized reaction conditions in hand (1 mol % of
[Ir(cod)Cl]2, 2 mol % of (S)-p-Tol-BINAP, 4 mol % AgOTf, 8
mol % Bu4NI, and 5 equiv of TMEDA in THP at 80 °C), we
attempted to expand the scope of the iridium-catalyzed ARO
reaction of oxabenzonorbornadiene 1a with various phenols.
The results were summarized in Table 4, from which it could
be seen that the structures of phenols had a very significant
Conditions: [Ir(cod)Cl]2 (1 mol %), (S)-p-Tol-BINAP (2 mol %),
AgOTf (4 mol %), Bu4NI (8 mol %), substrate 1a (0.2 mmol), halide
additive Bu4NI (0.2 mmol), TMEDA (1 mmol), and substituted
phenol (1 mmol) reacted in THP (2.0 mL) at 80 °C (oil bath
b
temperature). Determined by HPLC (Chiralcel AD-H or Chiralcel
OD-H column).
impact on reactivity and enantioselectivity. In general, the
reaction of 1a with para-substituted phenol offered better
results than those with ortho- and meta-substituted phenol
(Table 4, entries 1−3 and 6−8). Additionally, we observed
significant difference in the relative rates of reaction, with the
more acidic phenols adding faster. The reaction afforded better
yield and enantioselectivity when 1a reacted with monosub-
stituted phenols having electron-withdrawing groups than those
with electron-donating groups (Table 4, entries 1−3 and 6−8).
It was also noteworthy that phenol and 4-methoxyphenol for
the ring-opening were found to give moderate yield (74% and
60%, respectively) and high ee (93% and 94%, respectively)
(Table 4, entries 5 and 9), whereas the reaction of 1a with 4-
nitrophenol gave the corresponding product 2d in 70% yield
with 46% ee (Table 4, entry 4). Phenols having multi-
substituted groups also showed high reactivity and moderate to
good enantioselectivity (Table 4, entries 10−12 and 14−17).
For instance, the reactions of 1a with 2,3-dichlorophenol and
2,4-dichlorophenol gave the corresponding products 2j and 2k
in high yields (80% vs 96%) with excellent ee (98% vs 90%),
respectively (Table 4, entries 10 and 11). The reactions of 1a
with phenols having electron-withdrawing multisubstituted
groups gave the corresponding products 2l−q in moderate
yields with good ee (Table 4, entries 12−17). Due to the steric
bulkiness of the tert-butyl group, the ring-opening reaction by
2,6-di-tert-butyl phenol did not afford any desired product 2r
(Table 4, entry 18).
To extend the scope of this reaction to other substrates, we
used substituted oxabenzonorbornadienes 1b, 1c, and 1d with
phenols to perform the reaction, and these results are
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a
Table 5. Scope of Ir-Catalyzed ARO of Oxabenzonorbornadienes 1b−d with Various Phenols
b
entry
substrate
R3
product
time (h)
yield (%)
ee (%)
1
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
1d
1d
4-Cl
3-Cl
2-Cl
3a
3b
3c
3d
3e
3f
4
4
4
3
3
3
3
3
8
8
8
5
6
6
87
87
83
75
71
87
92
82
74
45
47
42
45
46
82
66
55
75
79
75
70
93
60
50
50
48
84
51
2
3
4
2,3-dichloro
2,4-dichloro
2,5-dichloro
2-bromo-4-chloro
4-bromo-2-chloro
4-Cl
5
6
7
3g
3h
4a
4b
4c
4d
5a
5b
8
9
10
11
12
13
14
2,4-dichloro
4-bromo-2-chloro
4-chloro-3-methyl
4-Cl
3-Cl
a
Conditions: [Ir(cod)Cl]2 (1 mol %), ligand (2 mol %), AgOTf (4 mol %), Bu4NI (8 mol %), substrate 1 (0.2 mmol), halide additive Bu4NI (0.2
b
mmol), TMEDA (1 mmol), and phenol (1 mmol) reacted in THP at 80 °C (oil bath temperature). Determined by HPLC (Chiralcel AD-H or
Chiralcel OD-H column).
summarized in Table 5. Table 5 shows that all reactions of
substrates of oxabicyclic alkenes with various phenols
proceeded smoothly to give the expected products in high
yields with moderate to excellent enantioselectivities. Except for
the reaction of 1b with 2-chlorophenol which showed slightly
lower enantioselectivity (Table 5, entry 3), other reactions of
1b treated with other phenols gave the corresponding products
in considerable yields with moderate to good ee (up to 93% ee)
(Table 5, entries 1, 2, and 4−8). Furthermore, the structure of
the disubstituted groups of the oxabenzonorbornadienes has
substantial effect on the reaction. The reactions of electron-rich
1c and 1d with phenols, respectively, required a longer reaction
time and gave lower yields with inferior ee, when compared
with electron-deficient 1b (Table 5, entries 9−12 and 14),
whereas there was an exception that the product 5a was
obtained in moderate yield (45%) with 84% ee (Table 5, entry
13). It is also noteworthy that the reaction of 4-bromo-2-
chlorophenol with 1b affords the expected product 3h in good
yield (82%) with high ee (93%).
Scheme 1. Working Hypothesis for the ARO Reaction of
Oxabenzonorbornadiene 1a with Phenols
Based on our findings and observations, a plausible
mechanism has been proposed for the formation of the ring-
opened products 2 as shown in Scheme 1. The active catalyst of
chiral dimeric iridium complex A, [Ir((S)-p-Tol-BINAP)I]2, is
first formed through treatment of the precatalyst, [Ir(cod)Cl]2,
with AgOTf to remove the chloride and followed by the
addition of the (S)-p-Tol-BINAP ligand, which replaces the 1.5-
cyclooctadiene (cod) ligand, and then the addition of Bu4NI.
The oxygen atom and the double bond of oxabenzonorborna-
diene 1a are then reversibly coordinated to the iridium center
of the active catalyst to give the intermediate B, followed by the
oxidative insertion of iridium catalyst into the C−O bond forms
C. Then phenol nucleophile attack with configuration inversion
is proposed to occur in an SN2 displacement of the iridium
catalyst. Consequently, the product 2 is subsequently released
and the iridium complex A is regenerated.
CONCLUSIONS
■
In summary, we have developed that a highly regio- and
stereoselective iridium-catalyzed ring-opening of oxabenzonor-
bornadienes with phenols. It provides an efficient and practical
approach to the synthesis of optically active trans-2-substituted-
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NMR (400 MHz, CDCl3) δ 7.61 (d, J = 6.0 Hz, 1H), 7.29−7.11 (m,
4H), 6.96 (d, J = 8.4 Hz, 2H), 6.82 (d, J = 8.4 Hz, 1H), 6.52 (d, J = 9.6
Hz, 1H), 5.96 (d, J = 10.0 Hz, 1H), 5.16 (d, J = 10.0 Hz, 1H), 5.06 (d,
J = 10.0 Hz, 1H), 2.73 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 158.1,
135.3, 135.1, 131.8, 130.5, 129.4, 128.3, 128.2, 126.6, 125.4, 125.3,
121.7, 116.3, 114.1, 79.4, 72.2; MS (EI, 70 eV) m/z (%): 254.03 ([M
− H2O]+, 2), 148.97 (31), 145.04 (43), 143.98 (95), 129.95 (25),
127.95 (100), 116.02 (35), 114.99 (66), 64.95 (29); Anal. Calcd for
C16H13ClO2: C, 70.46; H, 4.80. Found: C, 70.31; H, 4.83.
1,2-dihydronaphthalen-1-ol derivatives in moderate to good
yields and excellent enantioselectivities under mild conditions.
Use of both Bu4NI and TMEDA improve the reaction rate and
yield in the present reaction. Additionally, the presence of
electron-withdrawing groups on the oxabenzonorbornadienes
and phenols are found to have positive impact on the reactivity
and enantioselectivity. Our results further reveal that the nature
of the chiral ligand has a significant impact on this ring-opening
reaction. Studies on further expansion of the scope and
synthetic utility of the Ir-catalyzed ARO reactions are also being
pursued in our laboratory. As the ring-opened products, cyclic
alcohols with two chiral centers, are biologically important
compounds, future study will be focused on evaluating the
biological and pharmaceutical activities of these compounds.
(1S,2S)-2-(2-Chlorophenoxy)-1,2-dihydronaphthalen-1-ol
(2c). Following general procedure I, 2c was obtained as a white
crystalline solid (40.8 mg, 75%). The ee was determined to be 95%
using HPLC analysis on a Chiralcel OD-H column (hexane/2-
propanol = 95/5, 1.0 mL/min, λ = 254 nm). Retention times were
21.0 min (major) and 24.6 min (minor); Rf = 0.29 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 128−129 °C. [α]25D = +32.1
(c = 1.00, CHCl3). IR (KBr, cm−1) 3341(br), 2919(m), 2851(w),
1634(m), 1583(m), 1480(s), 1278(s), 1041(s), 892(m), 767(m),
EXPERIMENTAL SECTION
■
1
691(m); H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 6.8 Hz, 1H),
Only representative procedures and characterization of the products
are described here. Full details are presented in the Supporting
Information.
7.42−7.12 (m, 5H), 6.99−6.94 (m, 2H), 6.52 (d, J = 10.0 Hz, 1H),
6.05 (d, J = 10.0 Hz, 1H), 5.30 (d, J = 9.6 Hz, 1H), 5.11 (d, J = 10.2
Hz, 1H), 2.88 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 153.4, 135.4,
131.8, 130.6, 129.2, 128.3, 128.0, 127.8, 126.5, 125.9, 125.1, 124.1,
122.5, 115.9, 82.0, 72.5; MS (EI, 70 eV) m/z (%): 254.06 ([M −
H2O]+, 3), 145.06 (80), 143.68 (90), 128.19 (40), 127.55 (60), 116.08
(43), 114.96 (100); Anal. Calcd for C16H13ClO2: C, 70.46; H, 4.80.
Found: C, 70.18; H, 4.84.
General Procedure I for the ARO Reactions of Oxabenzo-
norbornadienes 1a−1d with Phenols. A 5.0 mL round-bottom
flask fitted with a reflux condenser was flame-dried under a stream of
nitrogen and cooled to room temperature. [Ir(cod)Cl]2 (1.3 mg, 1.0
mol %) and (S)-p-Tol-BINAP (2.7 mg, 2.0 mol %) were
simultaneously added and followed by the addition of anhydrous
THP (2.0 mL). After the mixture was stirred for about 20 min, silver
trifluoromethanesulfonate (2.0 mg, 4.0 mol %) was added. After
another 10 min, Bu4NI (5.9 mg, 8 mol %) was added and the mixture
was stirred for 10 min. To this mixture, substrate 1 (0.2 mmol) was
added, and then the mixture was heated. When the temperature of the
oil bath climbed to 80 °C, Bu4NI (73.8 mg, 1 equiv) and TMEDA
(116.1 mg, 5 equiv) were added and followed by the phenol (5 equiv).
The reaction temperature was maintained at 80 °C until completion as
judged by thin-layer chromatography. The solvent was removed in
vacuum, and the crude mixture was then poured into dichloromethane
and washed three times with 5% aqueous NaOH. The aqueous layers
were combined and back-extracted three times with dichloromethane.
The organic layers were combined, dried over anhydrous Na2SO4, and
then filtered. The filtrate was concentrated in vacuo, and the resulting
residue was purified by column chromatography on silica gel (silica
gel: 200−300 mesh) to give the target product.
(1S,2S)-2-(4-Nitrophenoxy)-1,2-dihydronaphthalen-1-ol
(2d). Following general procedure I, 2d was obtained as a white
crystalline solid (39.6 mg, 70%). The ee was determined to be 46%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 1.5 mL/min, λ = 254 nm). Retention times were
25.7 min (major) and 48.3 min (minor); Rf = 0.25 on silica gel (ethyl
acetate/petroleum ether = 1:5, v/v). mp 120−122 °C. [α]25D = +76.7
(c = 1.00, CHCl3). IR (KBr, cm−1) 3489(br), 3078(w), 2922(m),
2844(w), 1591(s), 1508(s), 1341(s), 1248(s), 1113(s), 983(s),
1
745(m), 750(s); H NMR (400 MHz, CDCl3) δ 8.20 (dd, J = 2.3,
9.2 Hz, 2H), 7.63−7.61 (m, 1H), 7.33−7.31 (m, 2H), 7.16−7.15 (m,
1H), 7.01 (dd, J = 1.6, 9.2 Hz, 2H), 6.59 (d, J = 9.6 Hz, 1H), 5.95 (d, J
= 9.6 Hz, 1H), 5.21 (s, 2H), 2.71 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 162.6, 141.8, 135.1, 131.5, 130.2, 128.6, 128.4, 126.8, 126.1,
125.5, 124.2, 115.5, 79.6, 72.0; MS (EI, 70 eV) m/z (%): 265.04 ([M
− H2O]+, 2), 144.15 (70), 143.55 (42), 127.82 (29), 116.04 (40),
114.94 (100), 109.05(21); Anal. Calcd for C16H13NO4: C, 67.84; H,
4.63; N, 4.94. Found: C, 67.68; H, 4.65; N, 5.01.
(1S,2S)-2-(4-Chlorophenoxy)-1,2-dihydronaphthalen-1-ol
(2a). Following general procedure I, 2a was obtained as a white
crystalline solid (45.2 mg, 83%). The ee was determined to be 98%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
16.5 min (major) and 23.4 min (minor); Rf = 0.24 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 125−126 °C. [α]25D = +97.5
(c = 1.00, CHCl3). IR (KBr, cm−1) 3298(br), 2928(w), 2851(w),
1590(m), 1485(s), 1233(s), 1032(m), 980(m), 839(m), 779(m),
(1S,2S)-2-Phenoxy-1,2-dihydronaphthalen-1-ol (2e). Follow-
ing general procedure I, 2e was obtained as a white crystalline solid
(35.2 mg, 74%). The ee was determined to be 93% using HPLC
analysis on a Chiralcel AD-H column (hexane/2-propanol = 90/10,
1.0 mL/min, λ = 254 nm). Retention times were 12.8 min (major) and
19.7 min (minor); Rf = 0.22 on silica gel (ethyl acetate/petroleum
ether = 1:10, v/v). mp 108−109 °C. [α]25 = +142.8 (c = 1.00,
D
CHCl3). IR (KBr, cm−1) 3251(br), 3029(w), 2853(w), 1599(s),
1
743(m); H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 6.8 Hz, 1H),
1
1494(s), 1247(s), 1060(s), 980(m), 745(s), 695(s); H NMR (400
7.32−7.23 (m, 4H), 7.12 (d, J = 6.4 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H),
6.52 (d, J = 9.6 Hz, 1H), 5.96 (d, J = 9.6 Hz, 1H), 5.16 (dd, J = 3.6,
10.0 Hz, 1H), 5.05 (d, J = 10.0 Hz, 1H), 2.65 (d, J = 3.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 156.0, 135.3, 131.8, 129.6, 129.3, 128.3,
128.1, 126.6, 126.4, 125.5, 125.3, 117.1, 79.4, 72.3; MS (EI, 70 eV) m/
z (%): 254.05 ([M − H2O]+, 10), 145.08 (23), 144.20 (92), 128.04
(100), 127.44 (44), 116.03 (68), 115.13 (86), 114.58 (45); Anal.
Calcd for C16H13ClO2: C, 70.46; H, 4.80. Found: C, 70.38; H, 4.81.
(1S,2S)-2-(3-Chlorophenoxy)-1,2-dihydronaphthalen-1-ol
(2b). Following general procedure I, 2b was obtained as a white
crystalline solid (46.2 mg, 85%). The ee was determined to be 76%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm); Retention times were
11.5 min (major) and 18.0 min (minor). Rf = 0.27 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 85−86 °C. [α]25D = +107.5
(c = 1.00, CHCl3). IR (KBr, cm−1) 3220(br), 3038(w), 2923(w),
2844(w), 1596(s), 1253(s), 1044(s), 905(m), 776(s), 743(s); 1H
MHz, CDCl3) δ 7.64 (d, J = 6.4 Hz, 1H), 7.32−7.25 (m, 4H), 7.12 (d,
J = 6.8 Hz, 1H), 7.01−6.95 (m, 3H), 6.52 (d, J = 9.6 Hz, 1H), 6.03 (d,
J = 10.0 Hz, 1H), 5.15 (dd, J = 10.0, 20.0 Hz, 2H), 2.68 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 157.3, 135.5, 131.9, 129.7, 129.0, 128.2,
128.0, 126.5, 126.1, 125.2, 121.5, 115.8, 79.0, 72.4; MS (EI, 70 eV) m/
z (%): 220.02 ([M − H2O]+, 5), 145.02 (62), 144.27 (54), 143.75
(100), 128.01 (15), 126.87 (49), 117.02 (23), 116.02 (45), 114.93
(88), 93.90 (43); Anal. Calcd for C16H14O2: C, 80.65; H, 5.92. Found:
C, 80.42; H, 5.98.
(1S,2S)-2-(p-Tolyloxy)-1,2-dihydronaphthalen-1-ol (2f). Fol-
lowing general procedure I, 2f was obtained as a white crystalline solid
(38.8 mg, 77%). The ee was determined to be 77% using HPLC
analysis on a Chiralcel AD-H column (hexane/2-propanol = 90/10,
1.0 mL/min, λ = 254 nm). Retention times were 15.6 min (major) and
25.4 min (minor); Rf = 0.26 on silica gel (ethyl acetate/petroleum
ether = 1:10, v/v). mp 79−80 °C. [α]25D = +130.8 (c = 1.00, CHCl3).
9760
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Article
IR (KBr, cm−1) 3201(br), 3029(w), 2920(w), 2851(w), 1612(w),
1507(s), 1227(s), 1032(s), 980(m), 824(m), 778(m), 743(m); 1H
NMR (400 MHz, CDCl3) δ 7.62 (d, J = 7.2 Hz, 1H), 7.29−7.20 (m,
2H), 7.10−7.07 (m, 3H), 6.85 (d, J = 8.4 Hz, 2H), 6.48 (d, J = 10.0
Hz, 1H), 6.00 (dd, J = 1.9, 10.0 Hz, 1H), 5.15 (d, J = 10.2 Hz, 1H),
5.05 (d, J = 10.2 Hz, 1H), 2.72 (s, 1H), 2.29 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 155.2, 135.6, 131.9, 130.8, 130.2, 128.8, 128.1, 128.0,
126.4, 126.3, 125.2, 115.9, 79.3, 72.4, 20.5; MS (EI, 70 eV) m/z (%):
233.81 ([M − H2O]+, 3), 145.06 (23), 143.95 (100), 126.95 (24),
114.95 (50) 108.00 (52), 106.78 (21); Anal. Calcd for C17H16O2: C,
80.93; H, 6.39. Found: C, 80.81; H, 6.44.
propanol = 90/10, 2.0 mL/min, λ = 254 nm). Retention times were
6.7 min (major) and 8.0 min (minor); Rf = 0.18 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 166−167 °C. [α]25
=
D
+127.8 (c = 1.00, CHCl3). IR (KBr, cm−1) 3219(br), 2921(w),
2851(w), 1578(m), 1454(s), 1287(s), 1041(m), 989(m), 777(s),
1
736(m); H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 6.8 Hz, 1H),
7.32−7.26 (m, 2H), 7.14 (d, J = 3.2 Hz, 3H), 6.93−6.85 (m, 1H), 6.54
(d, J = 10.0 Hz, 1H), 6.01 (d, J = 10.0 Hz, 1H), 5.30 (d, J = 10.0 Hz,
1H), 5.11 (d, J = 10.4 Hz, 1H), 2.77 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 154.7, 135.3, 134.2, 131.7, 129.5, 128.4, 128.1, 127.4, 126.5,
125.4, 125.1, 123.3, 113.4, 82.1, 72.4; MS (EI, 70 eV) m/z (%): 288.03
([M − H2O]+, 16), 207.02 (24), 163.96 (38), 161.91 (66), 145.12
(29), 144.19 (100), 126.09 (34), 116.00 (81), 114.72 (88); Anal.
Calcd for C16H12Cl2O2: C, 62.56; H, 3.94. Found: C, 62.41; H, 3.96.
(1S,2S)-2-(2,4-Dichlorophenoxy)-1,2-dihydronaphthalen-1-
ol (2k). Following general procedure I, 2k was obtained as a white
crystalline solid (58.8 mg, 96%). The ee was determined to be 90%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 2.0 mL/min, λ = 254 nm). Retention times were
8.3 min (major) and 9.9 min (minor); Rf = 0.24 on silica gel (ethyl
(1S,2S)-2-(m-Tolyloxy)-1,2-dihydronaphthalen-1-ol (2g). Fol-
lowing general procedure I, 2g was obtained as a white crystalline solid
(37.8 mg, 75%). The ee was determined to be 66% using HPLC
analysis on a Chiralcel AD-H column (hexane/2-propanol = 90/10,
1.0 mL/min, λ = 254 nm). Retention times were 10.6 min (major) and
19.4 min (minor); Rf = 0.26 on silica gel (ethyl acetate/petroleum
ether = 1:10, v/v). mp 62−63 °C. [α]25D = +113.5 (c = 1.00, CHCl3).
IR (KBr, cm−1) 3292(br), 3038(w), 2912(w), 2851(w), 1590(m),
1485(s), 1255(s), 1151 (m), 1047(s), 980(m), 779(s), 743(s),
1
acetate/petroleum ether = 1:10, v/v). mp 127−128 °C. [α]25
=
691(m); H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 6.8 Hz, 1H),
D
+102.0 (c = 1.00, CHCl3). IR (KBr, cm−1) 3394(br), 2932(w),
1643(s), 1477(s), 1263(m), 1099(m), 980(m), 779(s), 746(s); 1H
NMR (400 MHz, CDCl3) δ 7.63 (d, J = 6.8 Hz, 1H), 7.39 (d, J = 1.6
Hz, 1H), 7.32−7.25 (m, 2H), 7.17−7.11 (m, 2H), 6.89 (d, J = 8.8 Hz,
1H), 6.51 (d, J = 10.0 Hz, 1H), 5.97 (d, J = 10.0 Hz, 1H), 5.26 (d, J =
10.4 Hz, 1H), 5.05 (d, J = 10.0 Hz, 1H), 2.90 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 152.2, 135.3, 131.7, 130.3, 129.5, 128.4, 128.1, 127.8,
126.8, 126.6, 125.3, 125.1, 124.9, 116.6, 82.1, 72.4; MS (EI, 70 eV) m/
z (%): 288.01 ([M − H2O]+, 7), 207.03 (21), 163.90 (54), 161.85
(88), 145.05 (20), 144.17 (100), 143.64 (70), 125.98 (21), 116.02
(63), 115.18 (77), 114.66 (56); Anal. Calcd for C16H12Cl2O2: C,
62.56; H, 3.94. Found: C, 62.30; H, 3.99.
7.30−7.23 (m, 2H), 7.17 (t, J = 7.6 Hz, 1H), 7.10 (d, J = 7.2 Hz, 1H),
6.81−6.74 (m, 3H), 6.49 (d, J = 10.0 Hz, 1H), 6.01 (d, J = 10.0 Hz,
1H), 5.17 (d, J = 10.0 Hz, 1H), 5.09 (dd, J = 1.4, 10.2 Hz, 1H), 2.72 (s,
1H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.4, 139.8,
135.6, 131.9, 129.4, 128.9, 128.2, 128.0, 126.4, 126.3, 125.2, 122.3,
116.7, 112.7, 79.1, 72.4, 21.5; MS (EI, 70 eV) m/z (%): 233.98 ([M −
H2O]+, 3), 145.04 (24), 143.95 (100), 126.87 (20), 114.93 (53)
107.99 (45), 106.96 (32); Anal. Calcd for C17H16O2: C, 80.93; H, 6.39.
Found: 80.75; H, 6.46.
(1S,2S)-2-(o-Tolyloxy)-1,2-dihydronaphthalen-1-ol (2h). Fol-
lowing general procedure I, 2h was obtained as a white crystalline solid
(32.8 mg, 65%). The ee was determined to be 75% using HPLC
analysis on a Chiralcel AD-H column (hexane/2-propanol = 90/10,
0.5 mL/min, λ = 254 nm). Retention times were 25.8 min (major) and
28.1 min (minor); Rf = 0.26 on silica gel (ethyl acetate/petroleum
(1S,2S)-2-(2,5-Dichlorophenoxy)-1,2-dihydronaphthalen-1-
ol (2l). Following general procedure I, 2l was obtained as a white
crystalline solid (52.6 mg, 86%). The ee was determined to be 77%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 2.0 mL/min, λ = 254 nm). Retention times were
5.7 min (minor) and 7.5 min (major); Rf = 0.31 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 109−110 °C. [α]25D = +68.5
(c = 1.00, CHCl3). IR (KBr, cm−1) 3288(br), 2926(w), 1582(m),
ether = 1:10, v/v). mp 113−114 °C. [α]25 = +170.2 (c = 1.00,
D
CHCl3). IR (KBr, cm−1) 3290(br), 2926(w), 2850(m), 1596(w),
1486(s), 1233(s), 1032(m), 980(m), 840(m), 779(m), 743(m),
1
655(m); H NMR (400 MHz, CDCl3) δ 7.64−7.62 (m, 1H), 7.31−
7.24 (m, 2H), 7.18−7.10 (m, 3H), 6.92−6.84 (m, 2H), 6.49 (dd, J =
1.6, 10.0 Hz, 1H), 6.03−5.97 (m, 1H), 5.21 (d, J = 10.4 Hz, 1H), 5.11
(d, J = 10.0 Hz, 1H), 2.62 (s, 1H), 2.26 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 155.4, 135.6, 131.9, 131.2, 128.8, 128.2, 128.0, 127.8, 126.9,
126.5, 126.4, 125.2, 121.2, 113.0, 79.4, 72.6, 16.5; MS (EI, 70 eV) m/z
(%): 234.05 ([M − H2O]+, 2), 145.02 (30), 143.95 (100), 128.01
(21), 126.99 (22), 116.03 (31), 114.94 (58) 107.99 (49), 106.78 (22);
Anal. Calcd for C17H16O2: C, 80.93; H, 6.39. Found: C, 80.72; H, 6.46.
(1S,2S)-2-(4-Methoxyphenoxy)-1,2-dihydronaphthalen-1-ol
(2i). Following general procedure I, 2i was obtained as a white
crystalline solid (32.2 mg, 60%). The ee was determined to be 94%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 2.0 mL/min, λ = 254 nm). Retention times were
12.5 min (major) and 20.7 min (minor); Rf = 0.14 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 92−93 °C. [α]25D = +109.2
(c = 1.00, CHCl3). IR (KBr, cm−1) 3221(br), 2914(w), 2828(w),
1
1473(s), 1229(m), 1047(m), 984(s), 778(s), 749(m); H NMR (400
MHz, CDCl3) δ 7.65 (d, J = 6.8 Hz, 1H), 7.32−7.25 (m, 3H), 7.13 (d,
J = 6.4 Hz, 1H), 6.97−6.93 (m, 2H), 6.54 (d, J = 10.0 Hz, 1H), 6.00
(d, J = 9.6 Hz, 1H), 5.28 (d, J = 10.0 Hz, 1H), 5.08 (d, J = 10.4 Hz,
1H), 2.83 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 153.8, 135.2,
133.1, 131.7, 131.1, 129.6, 128.4, 128.1, 126.6, 125.1, 125.1, 122.5,
122.4, 116.1, 82.1, 72.3; MS (EI, 70 eV) m/z (%): 287.95 ([M −
H2O]+, 6), 163.84 (40), 161.84 (60), 148.93 (33), 145.02 (100),
144.28 (59), 143.74 (95), 128.02 (23), 126.92 (53), 117.03 (26),
116.03 (47), 114.93 (98), 62.85 (19); Anal. Calcd for C16H12Cl2O2: C,
62.56; H, 3.94. Found: C, 62.33; H, 3.98.
(1S,2S)-2-(2,6-Dichlorophenoxy)-1,2-dihydronaphthalen-1-
ol (2m). Following general procedure I, 2m was obtained as a white
crystalline solid (12.8 mg, 21%). The ee was determined to be 43%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
12.0 min (major) and 16.2 min (minor); Rf = 0.30 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 74−75 °C. [α]25D = +69.0 (c
= 1.00, CHCl3). IR (KBr, cm−1) 3464(br), 2926(m), 2850(w),
1
1612(w), 1508(s), 1470(m), 1221(s), 1033(m), 772(m), 749(s); H
NMR (400 MHz, CDCl3) δ 7.63 (d, J = 6.4 Hz, 1H), 7.31−7.25 (m,
2H), 7.11 (d, J = 6.8 Hz, 1H), 6.87 (dd, J = 8.6, 27.4 Hz, 4H), 6.49 (d,
J = 9.6 Hz, 1H), 6.01 (d, J = 9.6 Hz, 1H), 5.15 (d, J = 10.0 Hz, 1H),
5.00 (d, J = 10.0 Hz, 1H), 3.77 (s, 3H), 2.74 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 154.4, 151.3, 135.5, 131.9, 128.8, 128.1, 128.0, 126.4,
126.3, 125.2, 117.2, 114.8, 80.0, 72.4, 55.7; MS (EI, 70 eV) m/z (%):
250.02 ([M − H2O]+, 3), 145.03 (10), 143.95 (63), 126.95 (15),
123.91 (100), 116.03 (22), 114.93 (45) 108.90 (45); Anal. Calcd for
C17H16O3: C, 76.10; H, 6.01. Found: C, 76.29; H, 5.98.
(1S,2S)-2-(2,3-Dichlorophenoxy)-1,2-dihydronaphthalen-1-
ol (2j). Following general procedure I, 2j was obtained as a white
crystalline solid (50.0 mg, 80%). The ee was determined to be 98%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
1
2359(w), 1568(w), 1445(s), 1244(s), 1041(m), 962(m), 779(m); H
NMR (400 MHz, CDCl3) δ 7.61 (d, J = 6.8 Hz, 1H), 7.34−7.26 (m,
4H), 7.13−7.11 (m, 1H), 7.02 (td, J = 1.6, 8.1 Hz, 1H), 6.52 (d, J = 9.6
Hz, 1H), 6.10 (dd, J = 1.8, 9.8 Hz, 1H), 5.33−5.22 (m, 2H), 2.77 (d, J
= 3.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 150.3, 135.3, 131.7,
129.3, 129.3, 129.0, 128.3, 128.2, 126.6, 125.9, 125.8, 125.1, 84.5, 72.9;
MS (EI, 70 eV) m/z (%): 306.00 ([M]+, 5), 287.94 (24), 163.61 (42),
161.84 (83), 145.02 (80), 144.20 (98), 143.64 (90), 130.76 (36),
128.04 (27), 127.04 (35), 125.94 (34), 117.99 (76), 116.04 (69),
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115.32 (44.13), 114.80 (100); Anal. Calcd for C16H12Cl2O2: C, 62.56;
H, 3.94. Found: C, 62.34; H, 3.97.
5.27 (d, J = 10.0 Hz, 1H), 5.05 (d, J = 10.0 Hz, 1H), 2.90 (d, J = 5.6
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 153.6, 135.8, 135.2, 131.7,
131.4, 129.5, 128.4, 128.1, 126.5, 125.3, 125.1, 116.7, 114.3, 114.1,
82.3, 72.4; MS (EI, 70 eV) m/z (%): 377.86 ([M − H2O + 2]+, 3),
251.86 (26), 249.83 (15), 143.96 (100), 144.97 (16), 116.01 (37),
114.97 (79); Anal. Calcd for C16H12Br2O2: C, 48.52; H, 3.05. Found:
C, 48.69; H, 3.08.
(1S,2S)-2-(4-Chloro-3-methylphenoxy)-1,2-dihydronaphtha-
len-1-ol (2n). Following general procedure I, 2n was obtained as a
white crystalline solid (51.5 mg, 90%). The ee was determined to be
60% using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
12.3 min (major) and 19.0 min (minor); Rf = 0.24 on silica gel (ethyl
(1S,2S)-6,7-Dibromo-2-(4-chlorophenoxy)-1,2-dihydronaph-
thalen-1-ol (3a). Following general procedure I, 3a was obtained as a
white solid (74.1 mg, 87%). The ee was determined to be 82% using
HPLC analysis on a Chiralcel AD-H column (hexane/2-propanol =
90/10, 1.0 mL/min, λ = 254 nm). Retention times were 18.3 min
(major) and 30.2 min (minor); Rf = 0.26 on silica gel (ethyl acetate/
acetate/petroleum ether = 1:10, v/v). mp 126−127 °C. [α]25
=
D
+103.7 (c = 1.00, CHCl3). IR (KBr, cm−1) 3260(br), 2920(w),
2851(w), 2359(m), 1597(w), 1477(s), 1232(m), 1169(m), 1048(m),
986(m), 859(m), 779(s)745(m), 669(m); 1H NMR (400 MHz,
CDCl3) δ 7.62 (d, J = 6.4 Hz, 1H), 7.29−7.21 (m, 3H), 7.11 (d, J = 6.8
Hz, 1H), 6.82 (s, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.51 (d, J = 10.0 Hz,
1H), 5.97 (d, J = 10.0 Hz, 1H), 5.15 (d, J = 10.4 Hz, 1H), 5.04 (d, J =
10.0 Hz, 1H), 2.72 (s, 1H), 2.32 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 155.8, 137.4, 135.4, 131.8, 129.8, 129.2, 128.3, 128.1, 126.5,
125.7, 125.2, 118.4, 114.4, 79.3, 72.3, 20.4; MS (EI, 70 eV) m/z (%):
268.08 ([M − H2O]+, 8), 207.02 (16), 144.19 (76), 143.67 (75),
142.00 (70), 116.02 (53), 114.97 (100), 106.95 (74); Anal. Calcd for
C17H15ClO2: C, 71.20; H, 5.27. Found: C, 71.05; H, 5.31.
petroleum ether = 1:10, v/v). mp 161−163 °C. [α]25 = +85.7 (c =
D
1.00, CHCl3). IR (KBr, cm−1) 3356(br), 2919(w), 2851(w), 2361(m),
1605(m), 1492(s), 1283(s), 1239(s), 1050(m), 892(m), 824(m),
772(m), 691(m); 1H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.36−
7.25 (m, 3H), 6.87 (d, J = 8.4 Hz, 2H), 6.41 (d, J = 10.0 Hz, 1H), 6.04
(d, J = 10.0 Hz, 1H), 5.12−5.01 (m, 2H), 2.76 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 156.8, 139.1, 133.6, 131.6, 131.4, 129.8,
129.2, 127.3, 125.1, 123.4, 123.0, 117.9, 78.2, 70.1; MS (EI, 70 eV) m/
z (%): 411.89 ([M − H2O + 2]+, 5), 303.89 (39), 301.86 (76), 299.91
(35), 194.94 (66), 192.89 (88), 130.00 (35), 129.23 (26), 128.08
(100), 127.48 (65), 114.03 (74), 113.10 (58); Anal. Calcd for
C16H11Br2ClO2: C, 44.64; H, 2.58. Found: C, 44.48; H, 2.60.
(1S,2S)-2-(2-Bromo-4-chlorophenoxy)-1,2-dihydronaphtha-
len-1-ol (2o). Following general procedure I, 2o was obtained as a
white crystalline solid (58.7 mg, 84%). The ee was determined to be
73% using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 2.0 mL/min, λ = 254 nm). Retention times were
8.6 min (major) and 9.5 min (minor); Rf = 0.22 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 126−128 °C. [α]25D = +44.4
(c = 1.00, CHCl3). IR (KBr, cm−1) 3296(br), 2922(m), 2851(w),
2361(m), 1577(w), 1470(s), 1261(m), 1044(s), 985(m), 777(m),
(1S,2S)-6,7-Dibromo-2-(3-chlorophenoxy)-1,2-dihydronaph-
thalen-1-ol (3b). Following general procedure I, 3b was obtained as a
white solid (74.8 mg, 87%). The ee was determined to be 66% using
HPLC analysis on a Chiralcel AD-H column (hexane/2-propanol =
90/10, 1.0 mL/min, λ = 254 nm). Retention times were 12.8 min
(major) and 28.3 min (minor); Rf = 0.28 on silica gel (ethyl acetate/
1
746(m); H NMR (400 MHz, CDCl3) δ 7.65−7.56 (m, 2H), 7.32−
7.11 (m, 4H), 6.87 (d, J = 8.8 Hz, 1H), 6.52 (d, J = 9.6 Hz, 1H), 5.99
(d, J = 10.0 Hz, 1H), 5.28 (d, J = 10.4 Hz, 1H), 5.05 (d, J = 10.4 Hz,
1H), 2.87 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 153.2, 135.3,
133.1, 131.7, 129.5, 128.5, 128.4, 128.1, 127.1, 126.5, 125.4, 125.1,
116.2, 113.9, 82.4, 72.4; MS (EI, 70 eV) m/z (%): 331.97 ([M −
H2O]+, 3), 207.88 (41), 207.00 (27), 205.85 (41), 148.94 (36), 145.03
(20), 143.99 (100), 116.01 (50), 115.00 (80); Anal. Calcd for
C16H12BrClO2: C, 54.65; H, 3.44. Found: C, 54.84; H, 3.40.
petroleum ether = 1:10, v/v). mp 148−150 °C. [α]25 = +72.5 (c =
D
1.00, CHCl3). IR (KBr, cm−1) 3350(br), 2920(w), 2844(w), 2361(w),
1
1593(s), 1475(s), 1246(s), 1054(m), 985(s), 879(m), 775(m); H
NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.36 (s, 1H), 7.23 (t, J = 8.0
Hz, 1H), 7.00 − 6.94 (m, 2H), 6.82 (d, J = 8.4 Hz, 1H), 6.41 (d, J =
10.0 Hz, 1H), 6.04 (d, J = 10.0 Hz, 1H), 5.07 (dd, J = 24.2, 10.6 Hz,
2H), 2.78 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 158.9, 139.1,
134.2, 133.6, 131.6, 131.4, 129.1, 127.4, 123.4, 123.0, 121.4, 116.3,
115.1, 78.2, 70.1; MS (EI, 70 eV) m/z (%): 411.88 ([M − H2O + 2]+,
5), 303.81 (48), 301.80 (100), 299.81 (48), 224.02 (25), 221.90 (27),
194.86 (77), 192.86 (94), 128.06 (96), 127.55 (79), 114.02 (72); Anal.
Calcd for C16H11Br2ClO2: C, 44.64; H, 2.58. Found: C, 44.48; H, 2.60.
(1S,2S)-6,7-Dibromo-2-(2-chlorophenoxy)-1,2-dihydronaph-
thalen-1-ol (3c). Following general procedure I, 3c was obtained as a
white solid (71.0 mg, 83%). The ee was determined to be 55% using
HPLC analysis on a Chiralcel AD-H column (hexane/2-propanol =
90/10, 1.0 mL/min, λ = 254 nm). Retention times were 17.4 min
(major) and 19.0 min (minor); Rf = 0.30 on silica gel (ethyl acetate/
(1S,2S)-2-(4-Bromo-2-chlorophenoxy)-1,2-dihydronaphtha-
len-1-ol (2p). Following general procedure I, 2p was obtained as a
white crystalline solid (60.2 mg, 86%). The ee was determined to be
94% using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 2.0 mL/min, λ = 254 nm). Retention times were
9.4 min (major) and 12.4 min (minor); Rf = 0.20 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 128−129 °C. [α]25D = +92.7
(c = 1.00, CHCl3). IR (KBr, cm−1) 3302(br), 2924(m), 2852(w),
2363(m), 1657(m), 1565(w), 1475(s), 1257(m), 1047(m), 978-
1
(m),823(m),774(m), 690(m); H NMR (400 MHz, CDCl3) δ 7.65−
7.54 (m, 2H), 7.29 (t, J = 6.2 Hz, 3H), 7.12 (d, J = 6.4 Hz, 1H), 6.85
(d, J = 8.8 Hz, 1H), 6.52 (d, J = 10.0 Hz, 1H), 5.98 (d, J = 9.6 Hz,
1H), 5.27 (d, J = 10.0 Hz, 1H), 5.06 (d, J = 10.0 Hz, 1H), 2.83 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 152.7, 135.2, 133.0, 131.7,
130.7, 129.5, 128.4, 128.1, 126.5, 125.3, 125.2, 125.1, 117.0, 113.8,
82.1, 72.4; MS (EI, 70 eV) m/z (%): 331.94 ([M − H2O]+, 3), 207.90
(54), 207.09 (27), 205.90 (52), 145.06 (34), 144.24 (74), 143.73
(100), 127.79 (10), 127.02 (20), 126.12 (10), 116.11 (47), 115.24
(85), 114.65 (52); Anal. Calcd for C16H12BrClO2: C, 54.65; H, 3.44.
Found: C, 54.87; H, 3.40.
petroleum ether = 1:10, v/v). mp 109−110 °C. [α]25 = +110.9 (c =
D
1.00, CHCl3). IR (KBr, cm−1) 3418(br), 2924(m), 2851(w), 2355(w),
1
1587(m), 1481(s), 1242(s), 1060(s), 893(m), 748(s), 694(m); H
NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.41−7.31 (m, 2H), 7.21 (t,
J = 7.8 Hz, 1H), 6.96 (dd, J = 12.0, 8.0 Hz, 2H), 6.39 (d, J = 9.6 Hz,
1H), 6.10 (d, J = 9.2 Hz, 1H), 5.21 (dd, J = 10.8, 2.8 Hz, 1H), 5.06 (d,
J = 10.8 Hz, 1H), 3.08 (d, J = 3.2 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 153.5, 139.1, 133.5, 131.8, 131.5, 130.6, 129.0, 128.7,
127.4, 123.4, 123.0, 123.0, 122.6, 116.5, 79.2, 70.1; MS (EI, 70 eV) m/
z (%): 411.87 ([M − H2O + 2]+, 6), 303.80 (48), 301.86 (81), 299.81
(54), 194.96 (79), 192.93 (100), 129.95 (44), 128.13 (81), 127.61
(84), 114.98 (45), 113.96 (76), 112.94 (61); Anal. Calcd for
C16H11Br2ClO2: C, 44.64; H, 2.58. Found: C, 44.49; H, 2.60.
(1S,2S)-2-(2,4-Dibromophenoxy)-1,2-dihydronaphthalen-1-
ol (2q). Following general procedure I, 2q was obtained as a white
crystalline solid (63.0 mg, 80%). The ee was determined to be 75%
using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 2.0 mL/min, λ = 254 nm). Retention times were
9.3 min (major) and 11.2 min (minor); Rf = 0.47 on silica gel (ethyl
acetate/petroleum ether = 1:5, v/v). mp 128−129 °C. [α]25D = +100.8
(c = 1.00, CHCl3). IR (KBr, cm−1) 3305(br), 2925(w), 1646(w),
(1S,2S)-6,7-Dibromo-2-(2,3-dichlorophenoxy)-1,2-dihydro-
naphthalen-1-ol (3d). Following general procedure I, 3d was
obtained as a white solid (69.0 mg, 75%). The ee was determined to
be 75% using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
14.7 min (major) and 17.0 min (minor); Rf = 0.23 on silica gel (ethyl
1
1471(s), 1262(s), 1044(s), 989(m), 779(s), 743(m); H NMR (400
MHz, CDCl3) δ 7.66 (d, J = 23.6 Hz, 2H), 7.34−7.11 (m, 4H), 6.80
(d, J = 8.0 Hz, 1H), 6.51 (d, J = 9.2 Hz, 1H), 5.97 (d, J = 9.2 Hz, 1H),
acetate/petroleum ether = 1:10, v/v). mp 128−130 °C. [α]25
=
D
+169.8 (c = 1.00, CHCl3). IR (KBr, cm−1) 3385(br), 2915(w),
9762
dx.doi.org/10.1021/jo3018507 | J. Org. Chem. 2012, 77, 9756−9765

The Journal of Organic Chemistry
Article
2845(w), 1655(m), 1580(m), 1454(s), 1265(m), 1047(m), 988(m),
884(m), 764(m); H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.37
obtained as a white solid (83.0 mg, 82%). The ee was determined to
be 93% using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
25.2 min (major) and 30.2 min (minor); Rf = 0.28 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 159−161 °C. [α]25D = +79.3
(c = 1.00, CHCl3). IR (KBr, cm−1) 3352(br), 2922(m), 2851(m),
2359(m), 1582 (m), 1476(s), 1244(m), 1059(m), 980(m), 887(m),
752(m); 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.55 (d, J = 2.4
Hz, 1H), 7.36−7.31 (m, 2H), 6.83 (d, J = 8.8 Hz, 1H), 6.42 (dd, J =
2.0, 10.0 Hz, 1H), 6.05 (dd, J = 1.6, 10.0 Hz, 1H), 5.20 (d, J = 10.4 Hz,
1H), 5.02 (d, J = 10.8 Hz, 1H), 2.90 (s, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 153.0, 138.8, 133.4, 132.5, 131.7, 131.5, 131.4, 128.5,
127.7, 124.3, 123.5, 123.1, 118.2, 112.9, 79.4, 70.1; MS (EI, 70 eV) m/
z (%): 489.72 ([M − H2O + 2]+, 5), 303.89 (39), 301.86 (92), 299.78
(58), 208.08 (74), 206.93 (43), 206.04 (62), 195.16 (57), 194.60 (54),
193.04 (88), 113.99 (100), 112.95 (82); Anal. Calcd for
C16H10Br3ClO2: C, 37.72; H, 1.98. Found: C, 37.53; H, 2.00
1
(s, 1H), 7.15 (d, J = 4.8 Hz, 2H), 6.86 (t, J = 8.8 Hz, 1H), 6.42 (dd, J =
10.0, 1.6 Hz, 1H), 6.07 (d, J = 10.0 Hz, 1H), 5.23 (d, J = 10.8 Hz, 1H),
5.07 (d, J = 10.8 Hz, 1H), 2.94 (s, 1H); 13C NMR (100 MHz, DMSO-
d6) δ 155.0, 139.0, 133.5, 132.9, 131.8, 131.5, 128.9, 128.6, 127.7,
123.5, 123.1, 123.0, 121.6, 114.7, 79.6, 70.1; MS (EI, 70 eV) m/z (%):
445.81 ([M − H2O + 2]+, 14), 316.06 (16), 303.80 (48), 301.80
(100), 299.76 (49), 194.97 (77), 193.08 (66), 192.51 (49), 163.54
(52), 162.10 (51), 161.56 (62), 125.98 (73); Anal. Calcd for
C16H10Br2Cl2O2: C, 41.33; H, 2.17. Found: C, 41.16; H, 2.19.
(1S,2S)-6,7-Dibromo-2-(2,4-dichlorophenoxy)-1,2-dihydro-
naphthalen-1-ol (3e). Following general procedure I, 3e was
obtained as a white solid (65.7 mg, 71%). The ee was determined
to be 79% using HPLC analysis on a Chiralcel AD-H column (hexane/
2-propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
24.0 min (major) and 25.7 min (minor); Rf = 0.28 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 128−130 °C. [α]25
=
D
(1S,2S)-2-(4-Chlorophenoxy)-5,8-dimethoxy-1,2-dihydro-
naphthalen-1-ol (4a). Following general procedure I, 4a was
obtained as pale yellow oil (49.1 mg, 74%). The ee was determined
to be 60% using HPLC analysis on a Chiralcel OD-H column
(hexane/2-propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention
times were 23.5 min (major) and 29.3 min (minor); Rf = 0.15 on silica
+121.4 (c = 1.00, CHCl3). IR (KBr, cm−1) 3360(br), 2920(w),
2843(w), 1575(m), 1470(s), 1261(m), 1100(m), 984(m), 883(m),
756(m); 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.39 (d, J = 23.6
Hz, 2H), 7.19 (d, J = 7.2 Hz, 1H), 6.89 (d, J = 8.8 Hz, 1H), 6.42 (d, J
= 10.0 Hz, 1H), 6.05 (d, J = 9.6 Hz, 1H), 5.20 (d, J = 8.8 Hz, 1H), 5.02
(d, J = 10.8 Hz, 1H), 2.96 (d, J = 2.8 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6) δ 152.7, 139.0, 133.5, 131.7, 131.5, 129.9, 128.8, 128.5,
127.6, 125.5, 124.0, 123.4, 123.1, 117.7, 79.7, 70.2; MS (EI, 70 eV) m/
z (%): 445.82 ([M − H2O + 2]+, 5), 303.85 (40), 301.81 (85), 299.76
(41), 194.63 (45), 192.89 (85), 163.92 (67), 162.02 (100), 161.47
(45), 114.57 (46), 113.85 (57); Anal. Calcd for C16H10Br2Cl2O2: C,
41.33; H, 2.17. Found: C, 41.13; H, 2.20.
gel (ethyl acetate/petroleum ether = 1:5, v/v). [α]25 = +101.2 (c =
D
1.00, CHCl3). IR (KBr, cm−1) 3445(br), 2936(m), 2838(w), 2359(w),
1605(m), 1487(s), 1261(s), 1090(s), 993(s), 823(m), 750(m),
1
668(m); H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.4 Hz, 2H),
7.11 (d, J = 10.0 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 6.79 (s, 2H), 6.08
(dd, J = 4.8, 10.0 Hz, 1H), 5.25 (s, 1H), 4.98 (s, 1H), 3.79 (s, 6H),
2.81 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 156.1, 151.5, 150.0,
129.4, 125.9, 124.4, 123.3, 122.4, 121.0, 117.2, 111.6, 111.3, 74.3, 64.9,
56.2, 55.9; MS (EI, 70 eV) m/z (%): 314.08 ([M − H2O]+, 19),
205.05 (53), 204.29 (41), 203.78 (63), 188.80 (100), 173.94 (39),
129.93 (34), 127.87 (99); Anal. Calcd for C18H17ClO4: C, 64.97; H,
5.15. Found: C, 64.77; H, 5.19.
(1S,2S)-6,7-Dibromo-2-(2,5-dichlorophenoxy)-1,2-dihydro-
naphthalen-1-ol (3f). Following general procedure I, 3f was
obtained as a white solid (80.4 mg, 87%). The ee was determined
to be 75% using HPLC analysis on a Chiralcel AD-H column (hexane/
2-propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
12.5 min (minor) and 23.4 min (major); Rf = 0.30 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 162−164 °C. [α]25D = +60.8
(c = 1.00, CHCl3). IR (KBr, cm−1) 3370(br), 2919(w), 2851(w),
2362(m), 1582(w), 1478(s), 1262(m), 1055(m), 980(m), 831(m),
779(m), 691(m); 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.37−
732 (m, 2H), 6.96 (d, J = 10.8 Hz, 2H), 6.44 (d, J = 10.0 Hz, 1H), 6.07
(d, J = 9.6 Hz, 1H), 5.22 (d, J = 10.4 Hz, 1H), 5.05 (d, J = 10.8 Hz,
1H), 2.88 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 154.3, 139.0,
133.5, 132.8, 131.7, 131.5, 131.5, 128.9, 127.5, 123.4, 123.1, 122.4,
121.8, 116.6, 79.8, 70.3; MS (EI, 70 eV) m/z (%): 445.83 ([M − H2O
+ 2]+, 6), 303.87 (30), 301.85 (74), 299.85 (39), 194.89 (81), 192.60
(64), 163.90 (47), 161.88 (100), 114.04 (73), 97.06 (90); Anal. Calcd
for C16H10Br2Cl2O2: C, 41.33; H, 2.17. Found: C, 41.13; H, 2.20.
(1S,2S)-6,7-Dibromo-2-(2-bromo-4-chlorophenoxy)-1,2-di-
hydronaphthalen-1-ol (3g). Following general procedure I, 3g was
obtained as a white solid (93.1 mg, 92%). The ee was determined to
be 70% using HPLC analysis on a Chiralcel AD-H column (hexane/2-
propanol = 90/10, 0.3 mL/min, λ = 254 nm). Retention times were
82.0 min (major) and 85.6 min (minor); Rf = 0.30 on silica gel (ethyl
acetate/petroleum ether = 1:10, v/v). mp 146−148 °C. [α]25D = +90.8
(c = 1.00, CHCl3). IR (KBr, cm−1) 3372(br), 2918(w), 2851(w),
2359(m), 1560(w), 1471(m), 1288(m), 1051(m), 980(m), 869(m),
(1S,2S)-2-(2,4-Dichlorophenoxy)-5,8-dimethoxy-1,2-dihy-
dronaphthalen-1-ol (4b). Following general procedure I, 4b was
obtained as pale yellow oil (32.9 mg, 45%). The ee was determined to
be 50% using HPLC analysis on a Chiralcel OD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
26.2 min (major) and 33.7 min (minor); Rf = 0.17 on silica gel (ethyl
acetate/petroleum ether = 1:5, v/v). [α]25D = +94.0 (c = 1.00, CHCl3).
IR (KBr, cm−1) 3395(br), 2934(m), 2844(w), 1582(w), 1481(s),
1260(s), 1061(m), 980(m), 802(m), 759(m), 714(m); 1H NMR (400
MHz, CDCl3) δ 7.35 (s, 1H), 7.20−7.11 (m, 3H), 6.80 (s, 2H), 6.06
(dd, J = 4.6, 9.8 Hz, 1H), 5.30 (s, 1H), 5.00 (s, 1H), 3.81 (d, J = 9.2
Hz, 6H), 2.84 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 152.3, 151.5,
150.0, 130.1, 127.6, 126.6, 125.3, 124.7, 123.3, 122.1, 121.0, 117.7,
111.6, 111.4, 77.0, 65.7, 56.2, 56.0; MS (EI, 70 eV) m/z (%): 347.97
([M − H2O]+, 41), 221.02 (48), 205.03 (60), 204.04 (66), 188.68
(49), 163.93 (86), 162.13 (88), 161.57 (100), 97.87 (53); Anal. Calcd
for C18H16Cl2O4: C, 58.87; H, 4.39. Found: C, 58.67; H, 4.43.
(1S,2S)-2-(4-Bromo-2-chlorophenoxy)-5,8-dimethoxy-1,2-di-
hydronaphthalen-1-ol (4c). Following general procedure I, 4c was
obtained as pale yellow oil (38.5 mg, 47%). The ee was determined to
be 50% using HPLC analysis on a Chiralcel OD-H column (hexane/2-
propanol = 90/10, 1.0 mL/min, λ = 254 nm). Retention times were
27.8 min (major) and 36.6 min (minor); Rf = 0.19 on silica gel (ethyl
acetate/petroleum ether = 1:5, v/v). [α]25D = +61.6 (c = 1.00, CHCl3).
IR (KBr, cm−1) 3441(br), 2926(m), 2851(w), 1605(m), 1493(s),
1
743(m), 669(m); H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.59
(d, J = 2.4 Hz, 1H), 7.37 (s, 1H), 7.26 −7.23 (m, 1H), 6.86 (d, J = 8.8
Hz, 1H), 6.42 (dd, J = 10.0, 2.0 Hz, 1H), 6.07 (dd, J = 1.6, 10.0 Hz,
1H), 5.22 (d, J = 10.8 Hz, 1H), 5.02 (d, J = 11.2 Hz, 1H), 2.89 (d, J =
3.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 153.7, 139.0, 133.5,
132.7, 131.8, 131.5, 129.1, 128.8, 127.5, 125.9, 123.4, 123.1, 117.6,
113.5, 79.8, 70.2; MS (EI, 70 eV) m/z (%): 489.79 ([M − H2O + 2]+,
7), 303.84 (45), 301.79 (100), 299.83 (38), 209.93 (32), 208.12 (40),
207.58 (87), 205.94 (58), 194.92 (94), 192.89 (99), 113.83 (76),
112.90 (93); Anal. Calcd for C16H10Br3ClO2: C, 37.72; H, 1.98.
Found: C, 37.59; H, 2.00.
1
1256(s), 1210(s), 1150(m), 989(m), 853(m), 808(m), 736(m); H
NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.30 (d, J = 8.8 Hz, 1H),
7.09 (dd, J = 17.2, 9.2 Hz, 2H), 6.78 (s, 2H), 6.05 (dd, J = 9.8, 4.6 Hz,
1H), 5.29 (s, 1H), 4.99 (s, 1H), 3.79 (d, J = 6.4 Hz, 6H), 3.21 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 152.7, 151.4, 150.0, 132.8, 130.5,
125.5, 124.7, 123.3, 122.0, 120.9, 118.0, 113.5, 111.6, 111.4, 76.8, 65.5,
56.2, 56.0; MS (EI, 70 eV) m/z (%): 411.99 ([M + 2]+, 3), 205.08
(11), 203.94 (100), 161.00 (26), 130.91 (16); Anal. Calcd for
C18H16BrClO4: C, 52.52; H, 3.92. Found: C, 52.26; H, 3.96.
(1S,2S)-6,7-Dibromo-2-(4-bromo-2-chlorophenoxy)-1,2-di-
hydronaphthalen-1-ol (3h). Following general procedure I, 3h was
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(1S,2S)-2-(4-Chloro-3-methylphenoxy)-5,8-dimethoxy-1,2-
dihydronaphthalen-1-ol (4d). Following general procedure I, 4d
was obtained as pale yellow oil (29.1 mg, 42%). The ee was
determined to be 48% using HPLC analysis on a Chiralcel OD-H
column (hexane/2-propanol = 90/10, 1.0 mL/min, λ = 254 nm).
Retention times were 20.2 min (major) and 25.4 min (minor); Rf =
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (Nos. 20772036 and 21172081), Produce and Learning
and Research Project of Education Department of Guangdong
Province (No. 2011A090200039), and Key Laboratory of
Theoretical Chemistry of Environment, Ministry of Education
for financial support. We are also grateful to Dr. Qingqi Chen
of MedKoo Biosciences for critically reading and revising the
manuscript.
0.17 on silica gel (ethyl acetate/petroleum ether = 1:5, v/v). [α]25
=
D
+111.6 (c = 1.00, CHCl3). IR (KBr, cm−1) 3395(br), 2934(m),
2835(w), 1586(w), 1481(s), 1260(s), 1061(m), 983(m), 802(m),
758(m), 714(m); 1H NMR (400 MHz, CDCl3) δ 7.21 (d, J = 8.4 Hz,
1H), 7.11 (d, J = 10.0 Hz, 1H), 6.87−6.78 (m, 4H), 6.08 (dd, J = 9.4,
4.6 Hz, 1H), 5.25 (s, 1H), 4.97 (s, 1H), 3.78 (s, 6H), 2.82 (s, 1H),
2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.0, 151.5, 150.0,
137.1, 129.7, 126.2, 124.4, 123.4, 122.5, 121.0, 118.5, 114.5, 111.6,
111.3, 74.1, 64.9, 56.2, 55.9, 20.4; MS (EI, 70 eV) m/z (%): 328.04
([M − H2O]+, 18), 313.01 (22), 205.03 (76), 204.14 (100), 203.61
(46), 189.19 (88), 188.67 (93), 142.12 (58), 141.55 (41), 106.93 (98);
Anal. Calcd for C19H19ClO4: C, 65.80; H, 5.52. Found: C, 65.53; H,
5.56.
REFERENCES
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CHCl3). IR (KBr, cm−1) 3443(br), 2928(m), 2851(w), 2359(w),
1605(m), 1515(s), 1472(s), 1258(m), 1155(m), 1061(m), 980(m),
863(m), 808(m), 743(m); 1H NMR (400 MHz, CDCl3) δ 7.26−7.18
(m, 3H), 6.88 (dd, J = 8.8, 3.2 Hz, 2H), 6.68 (d, J = 2.8 Hz, 1H), 6.44
(d, J = 9.6 Hz, 1H), 5.89 (d, J = 9.6 Hz, 1H), 5.05 (dd, J = 31.8, 9.8
Hz, 2H), 3.91 (dd, J = 18.2, 3.4 Hz, 6H), 2.65 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 156.0, 148.8, 148.4, 129.6, 129.0, 128.1, 126.3, 124.6,
123.4, 117.1, 110.1, 109.1, 79.4, 72.1, 56.1, 56.1; MS (EI, 70 eV) m/z
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(40), 143.99 (31), 128.12 (55), 127.51 (46); Anal. Calcd for
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D
CHCl3). IR (KBr, cm−1) 3463(br), 2929(m), 2850(w), 2360(m),
1582(s), 1467(m), 1280(m), 1120(m), 990(m), 854(m), 775(m),
682(m); 1H NMR (400 MHz, CDCl3) δ 7.22−7.18 (m, 2H), 6.96 (d,
J = 5.2 Hz, 2H), 6.83 (d, J = 8.4 Hz, 1H), 6.67 (s, 1H), 6.45 (d, J = 9.6
Hz, 1H), 5.89 (d, J = 10.0 Hz, 1H), 5.07 (dd, J = 24.4, 9.6 Hz, 2H),
3.90 (d, J = 16.4 Hz, 6H), 2.70 (s, 1H); 13C NMR (100 MHz, CDCl3)
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116.3, 114.0, 110.1, 109.1, 79.3, 72.1, 56.1, 56.1; MS (EI, 70 eV) m/z
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(46), 143.96 (23), 127.99 (66), 114.97 (33); Anal. Calcd for
C18H17ClO4: C, 64.97; H, 5.15. Found: C, 64.70; H, 5.20.
ASSOCIATED CONTENT
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■
S
* Supporting Information
General section, copies of 1H and 13C NMR spectra of
compounds 2a−q, 3a−h, 4a−d, and 5a,b, HPLC conditions
and spectra of compounds 2a, 2c, 2e, 2i, 2j, 2k, 2p, and 3h, and
X-ray structure data for compound 2a. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: yangdq@scnu.edu.cn. Phone: +86 20 39310068. Fax:
+86 20 31040403.
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