An organocatalyst bearing stereogenic carbon and sulfur centers as an efficient promoter for enantioselective hydrosilylation of 1,4-benzooxazines

Article abstract of DOI:10.1021/jo400187e

The efficient and enantioselective hydrosilylation of 3-aryl-1,4- benzooxazines was achieved using an l-phenyl alanine derived new Lewis base catalyst bearing stereogenic carbon and sulfur centers. In the presence of 2 mol % of catalyst, a broad range of 3-aryl-1,4-benzooxazines were hydrosilylated to afford the corresponding chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxazine products with good to high yields (66-98%) and enantioselectivities (70-99% ee). This method provides an alternative approach with great practical application potential to access chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxazines.

Full text of DOI:10.1021/jo400187e

Note
pubs.acs.org/joc
An Organocatalyst Bearing Stereogenic Carbon and Sulfur Centers as
an Efficient Promoter for Enantioselective Hydrosilylation of 1,4-
Benzooxazines
Xiang-Wei Liu, Chao Wang,* Yan Yan, Yong-Qiang Wang, and Jian Sun*
Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People’s Republic
of China
S
* Supporting Information
ABSTRACT: The efficient and enantioselective hydrosilylation of 3-aryl-1,4-benzooxazines was achieved using an L-phenyl
alanine derived new Lewis base catalyst bearing stereogenic carbon and sulfur centers. In the presence of 2 mol % of catalyst, a
broad range of 3-aryl-1,4-benzooxazines were hydrosilylated to afford the corresponding chiral 3-aryl-3,4-dihydro-2H-1,4-
benzooxazine products with good to high yields (66−98%) and enantioselectivities (70−99% ee). This method provides an
alternative approach with great practical application potential to access chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxazines.
Given the attractiveness of organocatalytic asymmetric
hiral 3-substituted 3,4-dihydro-2H-1,4-benzooxazine is an
Cimportant structural motif that has been frequently seen hydrosilylation from the viewpoints of practical application
and economy, it is desirable to search for catalysts that could
furnish high enantioselectivity for the hydrosilylation of 1,4-
benzooxazine, ideally with low catalyst loading. In recent years,
we have made quite good progress in devising Lewis base
organocatalysts for asymmetric hydrosilylations.9,10 As part of
our continuing efforts in this field, we have successfully
developed a highly efficient new catalyst that could promote the
hydrosilylation of a broad range of 1,4-benzooxazines and
afford the corresponding 3-substituted 3,4-dihydro-2H-1,4-
benzooxazines in high yield and good to high enantioselectivity
(Scheme 1). Herein, we wish to report the results.
Since our previously developed S-chiral sulfinamide type
catalysts have shown exceptional reactivity and enantioselecti-
vity,9a,f−h,j we first checked the efficacies of these catalysts in a
model reaction of 1a. The N-sulfinyl L-prolinamide 5, a
hybridized catalyst that bears both chiral carbon and sulfur
centers and has been demonstrated to be highly enantiose-
lective for the hydrosilylation of β-enamino esters,9i was found
to give promising results. It smoothly drove the reaction to
completion and afforded the desired product 2a with 92% yield
and 59% ee (Table 1, entry 1). Although such results are on the
same mediocre level as those obtained with Zhang’s catalyst 3,7
we anticipated that a highly efficient catalyst might be
developed out of this special type of catalyst if a stereochemi-
in biologically interesting natural products such as Obscur-
inervidine and Niblinine and synthetic chiral drugs such as
Levofloxacin (Figure 1).1,2 The development of methods for
the preparation of such types of compounds has attracted
remarkable attention in the past few decades.3−5 The currently
available methods to access enantioenriched 3-substituted 3,4-
dihydro-2H-1,4- benzooxazines mainly rely on kinetic reso-
lution3 and stoichiometric synthesis.4 There are only a few
catalytic asymmetric versions. Satoh5a and Zhou5b−d developed
transition-metal-catalyzed asymmetric reduction of 1,4-ben-
zooxazines as an efficient method, which furnished various 3-
substituted 3,4-dihydro-2H-1,4-benzooxazines in excellent
enantioselectivity. Rueping6a,b and Thomas6c devised an
organocatalytic version using chiral phosphoric acids as
catalysts and Hantszch esters as reductants and also achieved
excellent results. Recently, Zhang has tried to implement
similar transformations via the more cost-efficient organo-
catalytic hydrosilylation approach that utilizes trichlorosilane as
the reductant and trans-4-hydroxy-L-proline derived Lewis base
3 (Figure 1) as the catalyst.7 This method, however, was found
to only afford low to moderate enantioselectivities (<76% ee in
most cases, 87% ee in only one case) after a range of 1,4-
benzooxazine substrates (1) were examined. An earlier attempt
̌
́
by Malkov and Kocovsky using L-valine derived Lewis base 4 to
catalyze the hydrosilylation of 1a (R1 = H, R2 = Ph) also
Received: February 2, 2013
resulted in low enantioselectivity (25% ee).8
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo400187e | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Figure 1. Natural products and drugs containing a chiral benzooxazine scaffold.
Scheme 1. Lewis Base Catalyzed Asymmetric Hydrosilylation of 1,4-Benzooxazines
Table 1. Asymmetric Hydrosilylation of 1,4-Benzooxazine
1a
decreased (entry 6). Notably, catalyst 7, the diastereomer of 6a
with opposite stereochemistry on the sulfur atom, exhibited
much lower enantioselectivity (entry 7), indicating that a
stereochemical match between the carbon center and the sulfur
center in the catalyst is crucial for the enantiocontrol.
a
catalyst
(amt (mol %))
temp
(°C)
yield
b
ee
(%)
c
entry
solvent
(%)
1
2
5 (20)
−20
−20
−20
−20
−20
−20
−20
−10
−40
-40
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
CHCl3
toluene
CH3CN
92
97
98
64
96
87
87
70
96
90
96
90
92
79
59
89
91
25
90
70
22
72
93
93
93
90
79
49
Next, we tested different reaction conditions in the 6b-
catalyzed hydrosilylation of 1a to optimize the catalytic
performance. While raising the reaction temperature from
−20 to −10 °C caused significant loss of reactivity and
enantioselectivity (entry 8),11 a slight increase in enantiose-
lectivity was observed when the temperature was lowered from
−20 to −40 °C (entry 9). The reaction proceeded equally well
when the catalyst loading was decreased from 20 to 10 mol %
(entry 10). Even with a further lowered catalyst loading of 2 mol
%, the reaction could still retain the excellent enantioselectivity and
only needs slightly longer time for completion (entry 11).
Solvent screening indicated that chloroform is almost as good
as dichloromethane (entry 12), whereas toluene and acetoni-
trile are much less effective (entries 13 and 14).
With the optimized conditions in hand, we then explored the
substrate scope of the present reaction system. A broad range of
3-aryl-1,4-benzooxazines 1 were tested in the presence of 2 mol
% of 6b. The results are summarized in Table 2. Substrates 1a−
j, bearing 3-aryl groups (R2) with different electronic
properties, were smoothly hydrosilylated to give the desired
3-aryl-3,4-dihydro-2H-1,4-benzooxazine products (2a−j) in
good to high yield (66−98%) and good to high enantiose-
lectivity (81−99% ee, entries 1−10). For the substrate 1k
bearing a relatively electron deficient 3-p-(trifluoromethyl)-
phenyl group, only moderate yield and enantioselectivity were
achieved (entry 11). Notably, 1l with a 3,2′-thienyl group also
proved to be a good substrate, affording 97% yield and 90% ee
(entry 12). In addition, substrates bearing a substituent such as
methyl on the 6-position (1m) were also found to be tolerable,
furnishing 79% yield and 90% ee (entry 13). It should be
pointed out that substrates bearing a 3-alkyl group such as 3-
methyl- and 3-isopropyl-1,4-benzooxazines proved to be not
suitable substrates, due to their poor stablility under the present
reaction conditions.
6a (20)
6b (20)
6c (20)
6d (20)
6e (20)
7 (20)
3
4
5
6
7
8
6b (20)
6b (20)
6b (10)
6b (2)
6b (2)
6b (2)
6b (2)
9
10
d
11
−40
−40
−40
−40
d
12
d
13
d
14
a
Unless otherwise noted, the reactions were performed with 1a (0.1
mmol) and HSiCl3 (0.3 mmol) in solvent at the designated
b
c
temperature for 36 h. Isolated yield. Determined by HPLC with a
chiral stationary phase. The product 2a was determined to have an R
configuration by comparison of the optical rotation with the literature
d
data. The reaction time is 48 h. If the reaction time is 24 h, the yield
is lower by about 20%, albeit with unaffected ee.
cally better matching skeleton was used. We first turned to the
noncyclic L-phenylalanine skeleton and prepared the analogous
new catalyst 6a (see the Supporting Information for its
synthesis and the absolute stereochemistry determination by X-
ray crystallography). Delightfully, it exhibited significantly
enhanced enantioselectivity. The ee value reaches 89% (entry
2). The set of analogues 6b−e derived from different amines
were then prepared to explore if the catalytic efficacy could be
further improved by changing the side amide group. 6b, bearing
a p-methoxyphenyl group, brought the ee value up to 91%
(entry 3). When the p-methoxyphenyl group was switched to
an o-methoxyphenyl group (6c), a substantial drop in
enantioselectivity was observed (entry 4). When this group
was further replaced with an aliphatic adamantyl group (6e),
both the enantioselectivity and the reactivity were dramatically
Although further experiments are still needed to rationalize
the high efficiency of the present catalyst system for the
B
dx.doi.org/10.1021/jo400187e | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
General Procedure for the Synthesis of Catalysts 6 and 7.
Catalysts 6 and 7 were synthesized according to our previously
reported procedures.9g,h
Table 2. 6b-Catalyzed Asymmetric Hydrosilylation of
Various 1,4-Benzooxazines
a
(S)-2-((S)-N-2-Dimethylpropan-2-ylsulfinamido)-N-3-diphenyl-
propanamide (6a): white solid, mp 90−92 °C; [α]D20 = −144.0° (c =
1
0.416, CHCl3); H NMR (300 MHz, CDCl3) δ (ppm) 9.44 (s, 1H),
7.66 (d, J = 8.3 Hz, 2H), 7.34−7.18 (m, 7H), 7.10 (t, J = 7.4 Hz, 1H),
4.45 (dd, J = 4.3, 11.5 Hz, 1H), 3.71 (dd, J = 4.3, 14.8 Hz, 1H), 2.89
(dd, J = 11.5, 14.8 Hz, 1H), 2.69 (s, 3H), 0.91 (s, 9H); 13C NMR (75
MHz, CDCl3) δ (ppm) 168.5, 138.5, 138.2, 129.1, 128.9, 128.6, 126.6,
124.3, 119.6, 72.7, 59.1, 35.2, 27.2, 23.5; ESI HRMS exact mass calcd
for (C20H26N2O2S + Na)+ m/z 381.1607, found m/z 381.1613; IR
(KBr) 3267 (m), 3060 (m), 2961 (m), 1691 (s), 1626 (m), 1557 (m),
1498 (m), 1428 (m), 1132 (m), 1045 (m), 877 (s), 843 (s), 754 (s),
712 (s) cm−1.
substrate
b
c
entry
R1
R2
yield (%)
ee (%)
1
H
Ph
1a
1b
1c
1d
1e
1f
96
93
97
88
97
91
98
93
66
68
74
97
79
93
83
92
92
86
80
83
99
95
92
70
90
97
2
H
p-MeO-Ph
p-Me-Ph
p-BnO-Ph
p-F-Ph
3
H
4
H
5
H
(S)-2-((S)-N-2-Dimethylpropan-2-ylsulfinamido)-N-(4-methoxy-
6
H
p-Cl-Ph
m-Cl-Ph
o-Cl-Ph
phenyl)-3-phenylpropanamide (6b): yellow solid, mp 120−122 °C;
20
[α]D = −120.8° (c = 0.36, CHCl3); 1H NMR (300 MHz, CDCl3) δ
7
H
1g
1h
1i
(ppm) 9.30 (s, 1H), 7.56 (d, J = 8.9 Hz, 2H), 7.32−7.18 (m, 5H), 6.85
(d, J = 9.0 Hz, 2H), 4.44 (dd, J = 4.2, 11.5 Hz, 1H), 3.79 (s, 3H), 3.71
(dd, J = 4.2, 14.8 Hz, 1H), 2.88 (dd, J = 11.6, 14.7 Hz, 1H), 2.68 (s,
3H), 0.90 (s, 9H); 13C NMR (75 MHz, CDCl3) δ (ppm) 168.1, 156.3,
138.6, 131.4, 129.1, 128.6, 126.6, 121.2, 114.0, 72.5, 59.1, 55.5, 35.2,
27.1, 23.5; ESI HRMS exact mass calcd for (C21H28N2O3S + Na)+ m/z
411.1713, found m/z 411.1712; IR (KBr) 3249 (m), 3330 (m), 2952
(m), 1679 (s), 1595 (m), 1538 (m), 1453 (m), 1305 (m), 1033 (m),
940 (s), 918 (s), 880 (s), 745 (s), 705 (s) cm−1.
8
H
9
H
1-naphthyl
2-naphthyl
p-CF3-Ph
2-thienyl
Ph
10
11
12
13
H
1j
H
1k
1l
H
6-Me
1m
a
Unless otherwise noted, the reactions were performed with 1 (0.1
mmol), 6b (0.02 mol), and HSiCl3 (0.3 mmol) in DCM (1 mL) at
−40 °C for 48 h. Isolated yield. Determined by HPLC with a chiral
b
c
(S)-2-((S)-N-2-Dimethylpropan-2-ylsulfinamido)-N-(2-methoxy-
stationary phase.
phenyl)-3-phenylpropanamide (6c): yellow solid, mp 90−92 °C;
20
[α]D = −86.3° (c = 0.454, CHCl3); 1H NMR (300 MHz, CDCl3) δ
(ppm) 8.74 (s, 1H), 8.23 (dd, J = 1.3, 7.9 Hz, 1H), 7.30−7.20 (m,
5H), 7.06 (t, J = 7.9 Hz, 1H), 6.95 (t, J = 7.8 Hz, 1H), 6.87 (d, J = 8.0
Hz, 1H), 4.38 (dd, J = 6.1, 8.8 Hz, 1H), 3.86 (s, 3H), 3.58 (dd, J = 6.1,
14.3 Hz, 1H), 2.99 (dd, J = 8.8, 14.2 Hz, 1H), 2.79 (s, 3H), 0.99 (s,
9H); 13C NMR (75 MHz, CDCl3) δ (ppm) 168.6, 149.1, 138.4, 129.3,
128.6, 127.2, 126.6, 124.5, 121.0, 120.7, 110.4, 69.4, 58.8, 55.9, 36.2,
28.6, 23.2; ESI HRMS exact mass calcd for (C21H28N2O3S + Na)+ m/z
411.1713, found m/z 411.1719; IR (KBr) 3311 (m), 2930 (m), 1680
(s), 1626 (m), 1600 (m), 1557 (m), 1429 (m), 1334 (s), 1230 (m),
1116 (m), 1030 (m), 883 (s), 746 (s), 712 (s) cm−1.
(S)-2-((S)-N-2-Dimethylpropan-2-ylsulfinamido)-N-(4-fluoro-
phenyl)-3-phenylpropanamide (6d): yellow solid, mp 80−85 °C;
[α]D20 = −125.9° (c = 0.686, CHCl3); 1H NMR (300 MHz, CDCl3) δ
(ppm) 9.49 (s, 1H), 7.64−7.59 (m, 2H), 7.32−7.21 (m, 5H), 7.00 (t, J
= 8.7 Hz, 2H), 4.44 (dd, J = 4.3, 11.5 Hz, 1H), 3.69 (dd, J = 4.3, 14.8
Hz, 1H), 2.88 (dd, J = 11.6, 14.8 Hz, 1H), 2.68 (s, 3H), 0.91 (s, 9H);
13C NMR (75 MHz, CDCl3) δ (ppm) 168.40, 159.3 (J = 241.6),
hydrosilylation of 3-aryl-1,4-benzooxazines in comparison to
others, the following structural features of the catalyst are
certainly critical contributors: (1) the Lewis basic S-chiral tert-
butylsulfinyl group, which has been previously demonstrated to
be an exceptionally powerful Lewis base activator,9g,h (2) the
combination of the chiral sulfur and carbon centers, which
endows the catalyst with excellent asymmetric induction
capability, and (3) the acyclic L-phenylalanine backbone,
which matches well with the cyclic structure of the substrate,
in contrast to catalyst 5 bearing a cyclic L-proline backbone,
which was previously shown to be an excellent catalyst for
acyclic substrates9c,f−h,j but is apparently much less suitable for
the present cyclic substrate system.
In conclusion, we have developed the asymmetric hydro-
silylation of 3-aryl-1,4-benzooxazines into a highly efficient and
enantioselective method for the construction of chiral 3-aryl-
3,4-dihydro-2H-1,4-benzooxazines using a newly synthesized
catalyst based on L-phenylalanine with both chiral carbon and
sulfur centers. With a remarkably low catalyst loading, a broad
range of 3-aryl-1,4-benzooxazines were hydrosilylated to afford
the corresponding chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxa-
zine products with generally high yields and enantioselectivities.
This method provides an alternative approach with great
practical application potential to access chiral 3-aryl-3,4-
dihydro-2H-1,4-benzooxazines.
138.4, 134.2, 129.1, 128.6, 126.7, 121.2 (J = 7.8 Hz), 115.5 (J = 22.3
Hz), 72.6, 59.1, 35.2, 27.1, 23.5; ESI HRMS exact mass calcd for
(C20H25FN2O2S + Na)+ requires m/z 399.1513, found m/z 399.1516;
IR (KBr) 3273 (m), 3063 (m), 2960 (m), 2927 (m), 1690 (s), 1557
(m), 1434 (m), 1213 (s), 1157(m), 1101 (m), 1044 (m), 923 (s), 747
(s), 712 (s) cm−1.
(S)-N-((3R,5R,7R)-Adamantan-1-yl)-2-((S)-N-2-dimethylpropan-2-
ylsulfinamido)-3-phenylpropanamide (6e): white solid, mp 85−86
20
°C; [α]D = −106.8° (c = 0.56, CHCl3); 1H NMR (300 MHz,
CDCl3) δ (ppm) 7.26−7.14 (m, 5H), 7.04 (s, 1H), 4.19 (dd, J = 4.4,
11.4 Hz, 1H), 3.57 (dd, J = 4.4, 14.7 Hz, 1H), 2.77 (dd, J = 11.6, 14.8
Hz, 1H), 2.61 (s, 3H), 2.05 (s, 9H), 1.67 (s, 6H), 0.84 (s, 9H); 13C
NMR (75 MHz, CDCl3) δ (ppm) 168.8, 139.0, 129.1, 128.5, 126.4,
72.1, 59.0, 52.3, 41.3, 36.4, 35.2, 29.4, 26.8, 23.4; ESI HRMS exact
mass calcd for (C24H36N2O2S + Na)+ m/z 439.2390, found m/z
439.2385; IR (KBr) 3460 (w), 3270 (s), 2901 (s), 2850 (m), 1674 (s),
1557 (m), 1434 (m), 1359 (s), 1186(m), 1102 (m), 1042 (m), 864
(s), 703 (m) cm−1.
EXPERIMENTAL SECTION
■
General Experimental Methods. All starting materials were of
the highest commercially available grade and were used without
further purification. All reactions were performed under an argon (Ar)
atmosphere unless otherwise specified. All solvents used in the
reactions were dried and distilled according to the standard procedure
prior to use, and other chemicals were purchased and used as received.
Substrates 1a,5c,d,6a,7 1b,6a,7 1c,5c,d,6a,7 1d,7 1e,5c,d,6a,7 1f,5c,d 1g,5d,6a,7
1h,7 1j,5c 1k,5d and 1l,7 products 2a,5c,d,6a,7 2b,6a,7 2c,5c,d,6a,7 2d,7
2e,5c,d,6a,7 2f,5c,d 2g,5d,7 2h,7 2j,5c 2k,5d and 2l,7 and catalyst 59g,h are
known compounds.
(S)-2-((R)-N,2-dimethylpropan-2-ylsulfinamido)-N,3-diphenylpro-
20
1
panamide (7): white solid; [α]D = −124.0° (c = 0.1, CHCl3); H
NMR (300 MHz, CDCl3) δ (ppm) 9.63 (s, 1H), 7.58−7.57 (m, 2H),
7.29−7.27 (m, 6H), 7.22−7.19 (m, 1H), 7.06 (t, J = 7.4 Hz, 1H), 4.45
(dd, J = 5.3, 9.2 Hz, 1H), 3.65 (dd, J = 9.2, 14.0 Hz, 1H), 2.89 (s, 3H),
C
dx.doi.org/10.1021/jo400187e | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
2.88 (dd, J = 5.3, 14.1 Hz, 1H), 1.15 (s, 9H); 13C NMR (75 MHz,
CDCl3) δ (ppm); 167.4, 138.3, 137.8, 129.6, 128.8, 128.5, 126.7,
123.9, 119.3, 59.1, 36.1, 35.1, 22.7; ESI HRMS exact mass calcd for
(C20H26N2O2S + Na)+ m/z 381.1607, found m/z 381.1613; IR (KBr)
3274 (m), 3061 (m), 2960 (s), 1683 (s), 1557 (s), 1497 (m), 1313
(s), 1251(s), 1135 (m), 1037 (s), 879(s), 754 (s), 711 (m) cm−1.
General Procedure for the Synthesis of Substrates 1.12 To a
solution of aryl methyl ketone A (10 mmol) in ethyl acetate (20 mL)
Hz, 1H), 7.60−7.49 (m, 3H), 6.93−6.84 (m, 2H), 6.78−6.73 (m, 2H),
5.37 (dd, J = 2.3, 8.3 Hz, 1H), 4.53 (dd, J = 2.5, 10.7 Hz, 1H), 4.13
(dd, J = 8.5, 10.7 Hz, 1H), 4.05 (br s, 1H); 13C NMR (150 MHz,
CDCl3) δ 143.7, 134.4, 134.1, 133.9, 130.9, 129.2, 128.6, 126.6, 125.8,
125.6, 124.5, 122.3, 121.5, 119.1, 116.7, 115.6, 70.2, 50.1; ESI HRMS
exact mass calcd for (C18H15NO + H)+ m/z 262.1226, found m/z
262.1221; IR (KBr) 3363 (w), 2923 (m), 1609 (m), 1499 (m), 1312
(s), 1277 (s), 1211 (s), 1057 (m), 884 (s), 753 (s) cm−1. The
enantiomers were analyzed by HPLC using a chiral OD-H column (n-
hexane/2-propanol 90/10, flow rate 1.0 mL/min, λ 254 nm): minor
enantiomer, tR = 38.5 min; major enantiomer, tR = 24.1 min; 95% ee.
(R)-6-Methyl-3-phenyl-3,4-dihydro-2H-benzo[b][1,4]oxazine
20
(2m): yellow oil; 17.8 mg (79% yield); [α]D = −31.0° (c = 0.258,
1
CHCl3); H NMR (300 MHz, CDCl3) δ (ppm) 7.41−7.34 (m, 5H),
6.75 (d, J = 8.7 Hz, 1H), 6.51 (d, J = 8.7 Hz, 1H), 6.50 (s, 1H), 4.51
(dd, J = 2.9, 8.5 Hz, 1H), 4.27 (dd, J = 2.9, 10.6 Hz, 1H), 3.97 (dd, J =
8.5, 10.6 Hz, 1H), 3.95 (br s, 1H), 2.25 (s, 3H); 13C NMR (151 MHz,
CDCl3) δ (ppm) 141.4, 139.3, 133.5, 130.9, 128.8, 128.3, 127.1, 119.4,
116.3, 115.9, 71.00, 54.3, 20.7; ESI HRMS exact mass calcd for
(C15H15NO + H)+ m/z 226.1226, found m/z 226.1222; IR (KBr)
2924 (m), 1606 (m), 1480 (m), 1313 (s), 1256 (s), 1184 (s), 1065
(s), 1026 (s), 884 (s), 753 (s) cm−1. The enantiomers were analyzed
by HPLC using a chiral IC column (n-hexane/2-propanol 98/2, flow
rate 1.0 mL/min, λ 254 nm): minor enantiomer, tR = 7.7 min; major
enantiomer, tR = 6.8 min; 97% ee.
was slowly added a solution of bromine (0.51 mL, 10 mmol) in ethyl
acetate (20 mL) at ambient temperature. After completion of the
reaction, the mixture was extracted with DCM. The combined extracts
were washed with water and dried over anhydrous sodium sulfate.
Solvents were evaporated under vacuum. Purification by flash column
chromatography (silica gel, hexane/EtOAc) afforded pure product B.
To a stirred biphasic solution of o-aminophenol (10 mmol), sodium
carbonate (2.12 g, 20 mmol), and tetra-n-butylammonium hydro-
sulfate (169.77 mg, 0.5 mmol) in DCM and H2O (50 and 20 mL,
respectively) was added a solution of α-brominated aryl methyl ketone
(10 mmol) in DCM (20 mL) at room temperature. The reaction
mixture was stirred for 24 h at the same temperature and was then
extracted with DCM. The combined extracts were washed with water,
dried over anhydrous sodium sulfate, and concentrated under vacuum.
The residue was purified by flash column chromatography to afford
pure product 1.
3-(Naphthalen-1-yl)-2H-benzo[b][1,4]oxazine (1i): yellow solid;
1H NMR (300 MHz, CDCl3): δ (ppm) 8.43 (d, J = 7.6 Hz, 1H), 7.94
(t, J = 7.6 Hz, 2H), 7.61−7.46 (m, 5H), 7.10 (t, J = 7.9 Hz, 1H), 7.02
(d, J = 7.9 Hz, 1H), 6.97 (d, J = 7.9 Hz, 1H), 4.97 (s, 2H); 13C NMR
(75 MHz, CDCl3): δ (ppm) 161.8, 146.4, 134.4, 133.9, 130.6, 130.4,
129.7, 128.9, 128.6, 127.8, 127.2, 126.3, 126.1, 125.4, 124.9, 122.5,
115.7, 65.6; ESI HRMS exact mass calcd for (C18H13NO + H)+ m/z
260.1070, found m/z 260.1070; IR (KBr) 2923 (m), 1609 (m), 1499
(m), 1312 (s), 1277 (s), 1211 (s), 1057 (m), 884 (s), 753 (s) cm−1.
6-Methyl-3-phenyl-2H-benzo[b][1,4]oxazine (1m): yellow solid;
1H NMR (300 MHz, CDCl3): δ (ppm) 7.96−7.92 (m, 2H), 7.51−
ASSOCIATED CONTENT
■
S
* Supporting Information
Text and figures giving experimental details and H and 13C
1
NMR and HPLC spectra of the products and a CIF file giving
the X-ray structure of compound 6a. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: wangchao@cib.ac.cn (C.W.); sunjian@cib.ac.cn (J.S.).
Fax: (+86)28-85222753.
Notes
The authors declare no competing financial interest.
7.50 (m, 3H), 7.29 (s, 1H), 6.98 (d, J = 8.1 Hz, 1H), 6.85 (d, J = 8.1
Hz, 1H), 5.05 (s, 2H), 2.36 (s, 3H); 13C NMR (75 MHz, CDCl3): δ
(ppm) 158.7, 144.0, 135.5, 133.5, 131.7, 131.0, 129.1, 128.7, 128.1
126.4, 115.1, 62.9, 20.6; ESI HRMS exact mass calcd for (C15H13NO +
H)+ m/z 224.1070, found m/z 224.1070; IR (KBr) 2924 (m), 1606
(m), 1480 (m), 1313 (s), 1256 (s), 1184 (s), 1065 (s), 1026 (s), 884
(s), 753 (s) cm−1.
ACKNOWLEDGMENTS
■
This project was supported by the National Natural Science
Foundation of China (Project Nos. 91013006 and 21272227).
REFERENCES
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E
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