Quinine-catalyzed asymmetric domino Michael-cyclization reaction for the synthesis of spirocyclic oxindoles bearing two spiro quaternary centers and three consecutive stereocenters

Article abstract of DOI:10.1016/j.tet.2014.01.036

An efficient organocatalytic diastereo- and enantioselective method for the construction of spirocyclic oxindole derivatives bearing two spiro quaternary centers and three consecutive stereocenters via a domino Michael/cyclization process has been developed. Using commercially available quinine as catalyst, the reactions of 3-isothiocyanato oxindoles with unsaturated pyrazolones and unsaturated isoxazolones proceeded smoothly under mild reaction conditions for giving two classes of spirocyclic oxindole compounds in high to excellent yields with moderate to good diastereoselectivities and enantioselectivities. A plausible dual activation working model was tentatively proposed to account for the stereochemistry of the domino Michael/cyclization process.

Full text of DOI:10.1016/j.tet.2014.01.036

Tetrahedron 70 (2014) 1895e1902
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Quinine-catalyzed asymmetric domino Michael-cyclization reaction
for the synthesis of spirocyclic oxindoles bearing two spiro
quaternary centers and three consecutive stereocenters
,
,
,
Bao-Dong Cui a c, Shi-Wu Li a c, Jian Zuo a c, Zhi-Jun Wu b, Xiao-Mei Zhang a,
Wei-Cheng Yuan a
,
*
a National Engineering Research Center of Chiral Drugs, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
b Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
c University of Chinese Academy of Sciences, Beijing 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 August 2013
Received in revised form 14 December 2013
Accepted 20 January 2014
Available online 25 January 2014
An efficient organocatalytic diastereo- and enantioselective method for the construction of spirocyclic
oxindole derivatives bearing two spiro quaternary centers and three consecutive stereocenters via
a domino Michael/cyclization process has been developed. Using commercially available quinine as
catalyst, the reactions of 3-isothiocyanato oxindoles with unsaturated pyrazolones and unsaturated
isoxazolones proceeded smoothly under mild reaction conditions for giving two classes of spirocyclic
oxindole compounds in high to excellent yields with moderate to good diastereoselectivities and
enantioselectivities. A plausible dual activation working model was tentatively proposed to account for
the stereochemistry of the domino Michael/cyclization process.
Keywords:
Asymmetric catalysis
Organocatalysis
Spirooxindoles
Domino reaction
Quinine
Ó 2014 Published by Elsevier Ltd.
1. Introduction
contiguous stereocenters) has remained a formidable challenge
and is highly desirable.
The spirocyclic oxindole scaffold defines the characteristic
structural core of a number of biologically active synthetic and
natural products with activities in a variety of disease areas (Fig. 1).1
Nevertheless, it has been exactly shown that the well-defined
three-dimensional architecture and structural complexity of natu-
ral molecules are generally correlated with the specificity of their
biological activity.2 Therefore, the development of new methods for
efficient construction of various spirocyclic oxindole structural
motifs is most fascinating and significant in the potential drug
development. Consequently, a variety of strategies for the enan-
tioselective synthesis of diversely structured spirocyclic oxindole
compounds have been reported in the past few years.3 Despite the
substantial advances made thus far, the synthetic challenge of the
spiro motif continues to encourage the development of creative
methods to access these important spirocyclic structures.4 In this
context, exploring efficient methodology for the direct generation
of structurally complex spirocyclic oxindoles (particularly those
that contain highly strained spiro stereocenters and several
3-Isothiocyanato oxindoles, firstly synthesized by our group,5a
have recently emerged as versatile nucleophiles for the
* Corresponding author. E-mail addresses: yuanwc@cioc.ac.cn, yuanweicheng@
Fig. 1. Natural products and bioactive drug candidates containing spirocyclic oxindole
126.com (W.-C. Yuan).
core scaffolds.
0040-4020/$ e see front matter Ó 2014 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tet.2014.01.036

1896
B.-D. Cui et al. / Tetrahedron 70 (2014) 1895e1902
construction of diverse spirocyclic oxindoles through different
catalytic asymmetric processes. These methodologies mainly relied
on the nucleophilic additions of 3-isothiocyanato oxindoles to
various electrophiles by aldol-,5,6 Mannich-,6,7 and Michael-type
reaction.4ceg,8 In parallel, a large number of organocatalytic dom-
ino reactions with various cinchona alkaloid derivatives as catalysts
have been perceived as prospective solutions to the synthesis of
enantiometrically enriched oxindole compounds.3,9 Additionally,
we also noticed that unsaturated pyrazolones had been used as
a class of Michael acceptors for some asymmetric reaction.4d,10
Encouraged by these achievements and our own laboratory’s re-
cent successes in the construction of 3,30-disubstituted oxindole,11
we attempted to investigate the reactions of 3-isothiocyanato
oxindoles and unsaturated pyrazolones, as well as unsaturated
isoxazolones. It was observed that the reactions smoothly gave rise
to two classes of complex spirocyclic oxindole compounds, bearing
two spiro quaternary centers and three consecutive stereocenters,
with commercially available quinine as catalyst via a domino Mi-
chael/cyclization process under mild reaction conditions (Scheme
1). Herein, we wish to report the results of our endeavours on
this subject.
molecular sieve probably facilitated the stereoselectivity. There-
fore, we deliberately added 0.1 mL water into the reaction system to
examine the function of water in the reaction. It was observed that
the desired product could be smoothly obtained in 98% yield, but
with distinctly decreased level of diastereoselectivity and enan-
tioselectivity (Table 1, entry 19).
Fig. 2. Chiral organocatalysts screened in the domino reaction of 1a and 2a (Table 1).
Table 1
Optimization of reaction conditionsa
Scheme 1. Quinine-catalyzed domino Michael/cyclization process for the synthesis of
two classes of spirocyclic oxindole derivatives.
Entry
Solvent
4
Yieldb (%)
drc
eed (%)
1
2
3
4
5
6
7
8
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Mesitylene
CH2Cl2
CHCl3
THF
CH3CN
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
4a
4b
4c
4d
4e
4f
4g
4h
4e
4e
4e
4e
4e
4e
4e
4e
4e
4e
4e
83
40
95
95
94
96
97
95
88
94
96
80
96
90
42
Trace
96
97
98
51:49
82:18
87:13
74:26
88:12
89:11
88:12
93:7
85:15
88:12
78:22
88:12
78:22
88:12
d
77
30
47
45
90
60
81
46
90
88
63
78
63
90e
df
dg
71h
85i
46j
2. Results and discussion
Initially, 3-isothiocyanato oxindole 1a and 4-benzylidene-3-
methyl-1-phenyl-pyrazolone 2a were treated with 10 mol % Take-
moto catalyst 4a (Fig. 2) in toluene at 25 ꢀC, the desired Michael-
cyclization product 3a was observed in 83% yield, but with 77% ee
and only 51:49 dr (Table 1, entry 1). However, replacement of
Takemoto catalyst 4a by quinine thiourea catalyst 4b (Fig. 2) for the
model reaction gave a significant lower yield and lower ee value, in
spite of the higher diastereoselectivity (Table 1, entry 2). Never-
theless, performing the reaction with quinine derivatives 4c and 4d
(Fig. 2), product 3a could be obtained in excellent yield but with
moderate diastereo- and enantioselectivity, respectively (Table 1,
entries 3 and 4). Gratifyingly, the same reaction proceeded
smoothly with commercially available quinine (4e) (Fig. 2) as cat-
alyst and afforded 3a in high to 94% yield with 88:12 dr and 90% ee
(Table 1, entry 5). However, other natural cinchona alkaloids 4feh
(Fig. 2) furnished lower ee value than quinine (4e) for the reaction
of 1a and 2a (Table 1, entries 6e8 vs entry 5). Afterwards, using
10 mol % 4e as catalyst, reactions run in other solvents (e.g.,
mesitylene, CH2Cl2, CHCl3, THF, CH3CN) were inferior to those
performed in toluene with respect to yield or enantioselectivity
(Table 1, entries 9e13 vs entry 5). Cooling the reaction to 0 ꢀC led to
a set of acceptable results, but a longer reaction time was required
(Table 1, entry 14). Furthermore, lowering the reaction temperature
to ꢁ20 ꢀC resulted in a significant decrease in yield with prolonged
reaction time (Table 1, entry 15). Unfortunately, further lowering to
ꢁ40 ꢀC, the reaction could hardly provide the product 3a (Table 1,
entry 16). In contrast, elevating the reaction temperature to 50 ꢀC
had a detrimental effect on the diastereo- and enantioselectivity
9
10
11
12
13
14
15
16
17
18
19
d
70:30
88:12
56:44
a
Unless otherwise noted, the reactions were performed with 0.1 mmol 1a and
0.12 mmol 2a in the presence of 10 mol % catalyst in 5.0 mL solvent at 25 ꢀC for 0.5 h.
b
Isolated yields of 3a.
Determined by HPLC analysis.
Enantiomeric excess for major diastereoisomers determined by chiral HPLC
c
d
analysis.
e
The reaction was performed at 0 ꢀC for 3.0 h.
f
The reaction was performed at ꢁ20 ꢀC for 12.0 h.
g
The reaction was performed at ꢁ40 ꢀC for 24.0 h.
h
The reaction was performed at 50 ꢀC for 0.5 h.
i
ꢀ
50 mg 4 A molecular sieve was used.
0.1 mL water was added into the reaction system.
j
With optimized reaction conditions in hand (Table 1, entry 5),
the reaction scope was examined next (Table 2). Firstly, with 3-
isothiocyanato oxindole 1b as nucleophilic reagent, diverse un-
saturated pyrazolones 2aeg were investigated to examined the
effects of the electronic properties and the steric hindrance of the
aromatic group on reactivity, diastereoselectivity and enantiose-
lectivity (Table 2, entries 1e7). Regardless of electron-donating
ꢀ
(Table 1, entry 17). The use of 4 A molecular sieve as additive led to
slight decrease in enantioselectivity (Table 1, entry 18 vs 5). From
ꢀ
this we speculated that the small amount water absorbed by 4 A

B.-D. Cui et al. / Tetrahedron 70 (2014) 1895e1902
1897
groups or electron-withdrawing groups on the phenyl ring of un-
saturated pyrazolones 2, all the reactions proceeded smoothly to
afford the desired products 3beg in 90e95% yield with 76e92% ee
(Table 2, entries 1e6). Moreover, a 1-naphthyl-based unsaturated
pyrazolones 2g also gave rise to the corresponding spirocyclic
oxindole 3h in high yield with moderate diastereoselectivity and
excellent enantioselectivity (Table 2, entry 7). Subsequently,
replacing the N-ethyl oxindole 1b with N-benzyl oxindole 1c as
nucleophilic reagent for further examining the scope and limitation
product 3t in excellent yield and diastereoselectivity, but with
hardly any enantioselectivity (Table 2, entry 19).
To further expand the substrate scope, a series of
b-aryl-
substituted
a,b
-unsaturated isoxazolones12 were selected as elec-
trophilic reagent by reacting with 3-isothiocyanato oxindoles to
generate another class of spirocyclic oxindoles (Table 3). The re-
action between N-methyl 3-isothiocyanato oxindole 1a and
b-
phenyl- -unsaturated isoxazolone 5a proceeded smoothly in
a,b
CH2Cl2 at ꢁ40 ꢀC in the presence of 10 mol % quinine as catalyst,
providing the corresponding product 6a in 95% yield with 90:10 dr
and 74% ee (Table 3, entry 1). Similar results also could be obtained
with N-benzyl 3-isothiocyanato oxindole 1c as nucleophilic regent
(Table 3, entry 2). Further studies demonstrated that the electronic
properties of the aromatic group in unsaturated isoxazolone had
little or no effect on the reactivity and stereoselectivity (Table 3,
entries 3e5). The reaction also took place with heteroaromatic
substituents as thiophene in unsaturated isoxazolone in high yield
with good selectivity (Table 3, entry 6). A bulkier group, such as 2-
naphthyl group, also could be incorporate in to the unsaturated
isoxazolone and gave the corresponding optically active product 6g
with good results (Table 3, entry 7).
of the substrate, it was observed that different
b-aryl-substituted
a,b
-unsaturated pyrazolones, including a variation of substituents
containing electron-donating as well as electron-withdrawing
functionalities on the aryl moiety, also could be smoothly trans-
formed into the corresponding spirocyclic oxindoles 3iep in ac-
ceptable results (Table 2, entries 8e15). Furthermore, two
heteroaromatic pyrazolones 2o and 2p were successfully employed
for reacting with 3-isothiocyanato oxindole 1c under the standard
conditions, giving the expected products 3q and 3r in excellent
yield with good enantioselectivity, respectively, and thereby
broadening the scope of the reaction (Table 2, entry 16 and 17).
Ultimately, when a methyl group was introduced in the 5-position
of the oxindole ring, there was no effect on the reactivity and se-
lectivity of the reaction (Table 2, entry 18). Note that the
b-alkyl-
substituted -unsaturated pyrazolones (2q) could also participate
in the reaction with oxindole 1a to afford the corresponding
a,b
Table 3
Scope of the domino reaction of 3-isothiocyanato oxindoles 1 and unsaturated
isoxazolones 5a
Table 2
Scope of the domino reaction of 3-isothiocyanato oxindoles 1 and unsaturated
pyrazolones 2a
Entry
1
5
Time (h) 6/Yieldb (%) drc
eed (%)
1
2
3
4
5
6
7
1a Ar¼Ph (5a)
1
1
1
2
1
2
2
6a/95
6b/96
6c/93
6d/94
6e/94
6f/92
6g/93
90:10 74
1c Ar¼Ph (5a)
94:6
93:7
92:8
92:8
77
77
73
67
1c Ar¼4-MeC6H4 (5b)
1c Ar¼4-MeOC6H4 (5c)
1c Ar¼4-FC6H4 (5d)
1c Ar¼2-thienyl (5e)
1c Ar¼2-naphthyl (5f)
Entry
1
2
Time
(h)
3/Yieldb
(%)
drc
83:17
83:17
84:16
eed (%)
89:11 68
60:40 64
1
2
3
1b
1b
1b
Ar¼Ph (2a)
0.5
0.5
0.5
3b/92
3c/95
3d/92
91
92
86
a
Unless otherwise noted, the reactions were performed with 0.1 mmol 1 and
0.12 mmol 5 in the presence of 10 mol % quinine in 5.0 mL CH2Cl2 at ꢁ40 ꢀC for the
specified reaction time.
Ar¼3-MeC6H4 (2b)
Ar¼3,4-MeO2C6H3 (2c)
b
Isolated yields of 6.
Determined by HPLC analysis.
Enantiomeric excess for major diastereoisomers determined by chiral HPLC
4
1b
0.5
3e/95
88:12
88
c
d
analysis.
5
6
7
8
1b
1b
1b
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
1d
1a
Ar¼3-BrC6H4 (2e)
Ar¼2,4-Cl2C6H3 (2f)
Ar¼1-naphthyl (2g)
Ar¼Ph (2a)
0.5
3.0
0.5
1.0
0.5
0.5
0.5
2.0
0.5
3.0
0.5
1.0
1.0
1.0
3.0
3f/94
3g/90
3h/92
3i/93
3j/96
3k/95
3l/94
3m/95
3n/94
3o/90
3p/95
3q/95
3r/96
3s/95
3t/98
87:13
50:50
65:35
87:13
86:14
83:17
82:18
77:23
81:19
63:37
83:17
56:44
86:14
88:12
>99:1e
76
91/75
98/91
94
87
88
91
94
95
89/91
80
Scheme 2 outlines one transformation of the chiral product 3i
into another spirocyclic oxindole 7. By reacting 3i with methyl io-
dide and K2CO3 in acetone at room temperature for overnight,
compound 7 could be accessed in 82% yield with >99:1 dr and 86%
ee. And then, we determined the relative and absolute configura-
tion of the major stereoisomer b single-crystal X-ray analysis of the
compound 7, where the chiral centers were determined as (R,R,R)-
configuration (Scheme 2). Assuming a common reaction pathway,
the stereochemistry of the other compounds was tentatively
assigned by analogy.
9
Ar¼4-MeC6H4 (2h)
Ar¼3-MeOC6H4 (2i)
Ar¼4-MeOC6H4 (2j)
Ar¼2,4-MeO2C6H3 (2k)
Ar¼4-ClC6H4 (2l)
Ar¼2-BrC6H4 (2m)
Ar¼4-BrC6H4 (2n)
Ar¼2-furyl (2o)
Ar¼2-thienyl (2p)
Ar¼Ph (2a)
10
11
12
13
14
15
16
17
18
19
87/82
85
93
Additionally, based on previous studies about the
a-iso-
2q
2
thiocyanato imides or esters applied in the organocatalytic asym-
metric transformations4ceg,5,6,8,13 and our experimental results,
a dual activation working model is tentatively suggested in Scheme
3 to account for the stereochemistry of the domino Michael/cycli-
zation process. During the catalytic process, the two substrates
involved in the reaction are activated simultaneously by the tertiary
amine moiety (for 3-isothiocyanato oxindole) and 9-OH moiety (for
unsaturated pyrazolones or unsaturated isoxazolones) of the
a
Unless otherwise noted, the reactions were performed with 0.1 mmol 1 and
0.12 mmol 2 in the presence of 10 mol % quinine in 5.0 mL toluene at 25 ꢀC for the
specified reaction time.
b
Isolated yields of 3.
Determined by HPLC analysis.
Enantiomeric excess for major diastereoisomers determined by chiral HPLC
c
d
analysis, and the results in parentheses for minor diastereoisomers also determined
by chiral HPLC analysis.
e
Determined by 1H NMR of the crude reaction mixture.

1898
B.-D. Cui et al. / Tetrahedron 70 (2014) 1895e1902
respectively) spectra were recorded in CDCl3 and DMSO-d6. 1H NMR
chemical shifts are reported in ppm relative to tetramethylsilane
(TMS) with the solvent resonance employed as the internal stan-
dard. Data are reported as follows: chemical shift, multiplicity
(s¼singlet, br s¼broad singlet, d¼doublet, t¼triplet, q¼quartet,
m¼multiplet), coupling constants (Hertz) and integration. 13C NMR
chemical shifts are reported in parts per million from tetrame-
thylsilane (TMS) with the solvent resonance as the internal stan-
dard. Melting points were recorded on a Buchi Melting Point B-545.
4.2. General procedure for the synthesis of products 3
In an ordinary vial equipped with a magnetic stirring bar, the
compounds 2 (0.12 mmol,1.2 equiv) and quinine (3.24 mg,10 mol %,
0.01 mmol) was dissolved in 5.0 mL of freshly distilled toluene at
25 ꢀC, and then oxindoles 1 (0.1 mmol) was added. After comple-
tion of the reaction, as monitored by TLC, the reaction mixture was
directly purified by flash chromatography on silica gel (petroleum
ether/ethyl acetate¼10:1w3:1) to yield products 3.
Scheme 2. Transformation of product 3i into compound 7 and the X-ray structure of
compound 7.
catalyst quinine. In the first Michael addition step, the activated 3-
4.3. General procedure for the synthesis of products 6
isothiocyanato oxindole (from the si-face) attacks the
the re-face) of the unsaturated pyrazolones or unsaturated iso-
xazolones. In the succedent cyclization step, the -position of the
b-position (to
In an ordinary vial equipped with a magnetic stirring bar, the
compounds 5 (0.12 mmol,1.2 equiv) and quinine (3.24 mg,10 mol %,
0.01 mmol) was dissolved in 5.0 mL of freshly distilled CH2Cl2
at ꢁ40 ꢀC, and then oxindoles 1 (0.1 mmol) was added. After
completion of the reaction, as monitored by TLC, the reaction
mixture was directly purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate¼10:1w3:1) to yield products 6.
a
unsaturated pyrazolones or unsaturated isoxazolones approaches
the eNCS group of the 3-isothiocyanato oxindole resulting in the
desired spirocyclic oxindole derivatives with determinate
stereochemistry.
4.4. Transformation of product 3i into compound 7
To the mixture of 3i (54.2 mg, 0.1 mmol) and anhydrous K2CO3
(15.3 mg, 0.11 mmol) in 5 mL acetone was added CH3I (6.9
mL,
0.11 mmol) at 0 ꢀC. The resulting mixture was stirred overnight at
room temperature and then concentrated in vacuo. The residue was
directly purified by flash column chromatography on silica gel
(petroleum ether/ethyl acetate 3.5:1) to give the compound 7 as
white solid.
Scheme 3. Proposed working model for the domino Michael/cyclization process.
3. Conclusion
4.5. Characterization data and HPLC conditions of products 3,
6 and 7
In conclusion, we have developed an organocatalytic diastereo-
and enantioselective method for the construction of spirocyclic
oxindole derivatives bearing two spiro quaternary centers and three
consecutive stereocenters via a domino Michael/cyclization process.
The reaction utilizes 3-isothiocyanato oxindoles as nucleophilic re-
agents addition to unsaturated pyrazolones, as well as unsaturated
isoxazolones with commercially available quinine as catalyst under
mild reaction conditions, affording two classes of spirocyclic oxindole
compounds in high to excellent yields (90e96%) with moderate to
good diastereoselectivities (up to 94:6 dr) and enantioselectivities
(64e98% ee). Furthermore, a plausible working model was also pro-
posed on the basis of previous literature and our own investigation to
account for the stereochemistry of the domino Michael/cyclization
process. We believe that this methodology will be useful in diversity-
oriented library synthesis and the subsequent biological evaluation of
its members for medicinal chemistry.
20
4.5.1. Compound 3a. White solid, 94% yield; 88:12 dr, 90% ee; [a]
D
þ17.9 (c 1.07, CHCl3); mp 139.2e140.5 ꢀC; the ee was determined by
HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow rate 1.0 mL/
min,
l
¼254 nm, major diastereomer: tminor¼18.4 min,
tmajor¼5.7 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.58 (s, 3H),
3.12 (s, 3H), 4.93 (s,1H), 6.79 (d, J¼7.8 Hz,1H), 6.94 (d, J¼6.9 Hz, 2H),
7.13e7.22 (m, 5H), 7.36e7.41 (m, 3H), 7.72 (d, J¼7.5 Hz, 1H), 7.88 (d,
J¼7.8 Hz, 2H), 8.71 (s, 1H); 13C NMR (75 MHz, CDCl3)
d (major) 16.9,
26.6, 61.3, 73.5, 77.5, 108.9, 119.2, 124.2, 124.4, 125.4, 126.3, 127.8,
128.4,128.5,128.8,128.9,129.6,130.8,131.3,137.5,143.1,158.7,171.3,
173.3, 197.9; IR (KBr):
n 3062, 2962, 1709, 1613, 1596, 1498, 1471,
1365, 1263, 1157, 1100, 1023, 752, 733, 690, 591 cmꢁ1; HRMS (ESI):
Calculated for
489.1356.
C
27H22N4NaO2S [MþNa]þ: 489.1356, found:
20
4.5.2. Compound 3b. White solid, 92% yield; 83:17 dr, 91% ee; [a]
D
4. Experimental section
4.1. General
þ23.0 (c 1.06, CHCl3); mp 228.9e230.3 ꢀC; the ee was determined
by HPLC (Chiralpak AD-H, EtOH/hexane¼30:70, flow rate 1.0 mL/
min,
l
¼254 nm, major diastereomer: tminor¼10.5 min,
tmajor¼5.8 min); 1H NMR (300 MHz, CDCl3)
d (major) 0.99 (t,
Reagents were purchased from commercial sources and were
used as received unless mentioned otherwise. Reactions were
monitored by TLC. 1H NMR and 13C NMR (300 and 75 MHz,
J¼7.2 Hz, 3H), 2.62 (s, 3H), 3.43e3.52 (m, 1H), 3.74e3.83 (m, 1H),
4.90 (s, 1H), 6.77 (d, J¼7.8 Hz, 1H), 6.91 (d, J¼7.2 Hz, 2H), 7.08e7.20
(m, 5H), 7.34e7.40 (m, 3H), 7.71 (d, J¼6.9 Hz,1H), 7.87e7.90 (m, 2H),

B.-D. Cui et al. / Tetrahedron 70 (2014) 1895e1902
1899
8.63 (s,1H); 13C NMR (75 MHz, CDCl3)
73.6, 77.3, 108.9, 119.1, 124.0, 124.6, 125.4, 126.5, 128.0, 128.3, 128.6,
128.7,128.8,129.6,130.7,131.3, 137.6,142.2,158.7, 171.3, 172.7,198.0;
d
(major) 12.0,17.0, 35.2, 61.8,
2934,1717, 1613, 1596, 1498, 1469, 1368, 1315, 1215,1156, 1132, 1100,
754, 690 cmꢁ1; HRMS (ESI): Calculated for C28H23BrN4NaO2S
[MþNa]þ: 581.0617, found: 581.0606.
IR (KBr):
n 3123, 2964, 1728, 1613, 1596, 1499, 1468, 1369, 1264,
1216, 1153, 1120, 749, 689, 589 cmꢁ1; HRMS (ESI): Calculated for
4.5.7. Compound 3g. White solid, 90% yield; 50:50 dr, 91%, 75% ee;
20
C
28H24N4NaO2S [MþNa]þ: 503.1512, found: 503.1519.
[
a
]
þ116.2 (c 1.00, CHCl3); mp 143.4e144.8 ꢀC; the ee was de-
D
termined by HPLC (Chiralpak AD-H, EtOH/hexane¼20:80, flow rate
20
4.5.3. Compound 3c. White solid, 95% yield; 83:17 dr, 92% ee; [
a
]
1.0 mL/min,
l¼254 nm, one diastereomer: tminor¼4.7 min,
D
þ17.9 (c 1.07, CHCl3); mp 156.3e157.5 ꢀC; the ee was determined by
HPLC (Chiralpak AD-H, EtOH/hexane¼30:70, flow rate 1.0 mL/min,
tmajor¼6.7 min; the other diastereomer: tminor¼9.3 min,
tmajor¼9.8 min); 1H NMR (300 MHz, CDCl3)
d (one diastereomer)
l
¼254 nm, major diastereomer: tminor¼7.8 min, tmajor¼5.1 min); 1H
1.11 (t, J¼7.2 Hz, 3H), 2.44 (s, 3H), 3.48e3.57 (m, 1H), 3.73e3.82 (m,
1H), 5.51 (s, 1H), 6.68 (d, J¼7.8 Hz, 1H), 6.78e6.82 (m, 1H), 7.19e7.23
(m, 3H), 7.28e7.39 (m, 3H), 7.53 (d, J¼8.7 Hz, 1H), 7.73 (d, J¼8.1 Hz,
2H), 8.27 (s, 1H), 8.62 (d, J¼7.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
NMR (300 MHz, CDCl3)
d
(major) 1.02 (t, J¼7.2 Hz, 3H), 2.11 (s, 3H),
2.59 (s, 3H), 3.44e3.52 (m, 1H), 3.76e3.85 (m, 1H), 4.86 (s, 1H), 6.68
(s, 1H), 6.76e6.79 (m, 2H), 6.97e7.00 (m, 2H), 7.16e7.21 (m, 2H),
7.34e7.40 (m, 3H), 7.71 (d, J¼7.5 Hz, 1H), 7.88 (d, J¼7.8 Hz, 2H), 8.70
d
(one diastereomer) 12.2, 14.1, 35.5, 49.8, 73.5, 76.9, 108.7, 119.7,
(s, 1H); 13C NMR (75 MHz, CDCl3)
d
(major) 12.0, 17.0, 21.2, 35.2,
123.3, 124.6, 125.9, 126.3, 126.8, 128.9, 129.0, 129.2, 131.1, 132.9,
135.4, 135.9, 137.2, 142.2, 158.6, 169.0, 174.0, 196.5; IR (KBr): 3204,
2925, 2854, 1716, 1700, 1612, 1595, 1497, 1462, 1366, 1292, 1151,
61.6, 73.5, 77.4, 108.9, 119.1, 124.0, 124.6, 124.8, 125.4, 126.4, 126.5,
128.6, 128.7, 128.8, 129.3, 130.4, 130.5, 131.2, 137.5, 138.4, 142.2,
n
158.8, 171.3, 172.8, 198.0; IR (KBr):
n
3227, 2926, 1721, 1612, 1596,
1128, 1105, 753, 687 cmꢁ1
; HRMS (ESI): Calculated for
1490, 1468, 1368, 1215, 1156, 1129, 1101, 754, 689, 656 cmꢁ1; HRMS
(ESI): Calculated for C29H26N4NaO2S [MþNa]þ: 517.1669, found:
517.1669.
C
28H22Cl2N4NaO2S [MþNa]þ: 571.0733, found: 571.0742.
4.5.8. Compound 3h. White solid, 92% yield; 65:35 dr, 98%, 91% ee;
20
[
a
]
þ66.6 (c 0.60, CHCl3); mp 228.8e230.3 ꢀC; the ee was de-
D
20
4.5.4. Compound 3d. White solid, 92% yield; 84:16 dr, 86% ee; [
a
]
termined by HPLC (Chiralpak AD-H, EtOH/hexane¼10:90, flow rate
D
þ32.7 (c 1.20, CHCl3); mp 177.8e178.8 ꢀC; the ee was determined by
HPLC (Chiralpak AD-H, EtOH/hexane¼20:80, flow rate 1.0 mL/min,
1.0 mL/min,
l¼254 nm, major diastereomer: tminor¼13.6 min,
tmajor¼19.8 min; minor diastereomer: tminor¼25.6 min,
l
¼254 nm, major diastereomer: tminor¼22.7 min, tmajor¼11.7 min);
tmajor¼17.1 min); 1H NMR (300 MHz, CDCl3)
d
(majorþminor) 0.58
1H NMR (300 MHz, CDCl3)
d
(major) 0.93 (t, J¼6.9 Hz, 3H), 2.66 (s,
(t, J¼7.2 Hz, 2H), 0.86 (t, J¼7.2 Hz, 1H), 2.42 (s, 2H), 2.78 (s, 1H),
3.21e3.42 (m, 1H), 3.50e3.66 (m, 0.7H), 3.69e3.81 (m, 0.3H), 5.78
(s, 0.7H), 5.92 (s, 0.3H), 6.48e6.53 (m, 1H), 7.02e7.08 (m, 1H),
7.18e7.36 (m, 6.7H), 7.56 (d, J¼8.1 Hz, 1H), 7.68e7.81 (m, 5H), 8.15
(d, J¼8.7 Hz, 0.7H), 8.72e8.83 (m, 1.6H); 13C NMR (75 MHz, CDCl3)
3H), 3.35e3.42 (m, 1H), 3.50 (s, 3H), 3.56e3.63 (m, 1H), 3.69 (s, 3H),
4.79 (s, 1H), 6.37 (s, 1H), 6.50e6.55 (m, 2H), 6.70 (d, J¼7.8 Hz, 1H),
7.14e7.19 (m, 2H), 7.32e7.38 (m, 3H), 7.69 (d, J¼7.5 Hz, 1H),
7.85e7.88 (m, 2H), 8.77 (s, 1H); 13C NMR (75 MHz, CDCl3)
d (major)
12.1, 17.0, 35.1, 55.4, 55.5, 62.3, 73.7, 77.4, 108.8, 111.0, 111.1, 119.0,
120.5, 122.6, 122.7, 123.9, 124.5, 125.4, 126.7, 128.7, 131.1, 137.5,
142.2, 148.6, 149.0, 158.7, 171.4, 172.7, 198.1; IR (KBr):
1721, 1612, 1595, 1489, 1367, 1270, 1215, 1149, 1026, 755, 690,
656 cmꢁ1; HRMS (ESI): Calculated for C30H28N4NaO4S [MþNa]þ:
563.1723, found: 563.1706.
d
(majorþminor) 11.6, 12.0, 14.3, 17.0, 35.1, 35.2, 49.2, 55.9, 74.3,
74.6, 77.6, 78.0, 108.5, 108.8, 119.1, 119.8, 121.3, 123.4, 124.7, 125.3,
125.5, 125.6, 125.7, 127.2, 128.6, 128.7, 128.8, 129.1, 129.2, 129.3,
130.5, 133.5, 141.8, 158.2, 158.5, 169.8, 171.2, 173.6, 174.4, 197.2,
n 3263, 2931,
198.7; IR (KBr):
n 3227, 2926, 1717, 1612, 1596, 1498, 1365, 1215,
1158, 1127, 791, 755, 690 cmꢁ1; HRMS (ESI): Calculated for
C
32H26N4NaO2S [MþNa]þ: 553.1669, found: 553.1677.
4.5.5. Compound 3e. Light yellow solid, 95% yield; 88:12 dr, 88% ee;
20
[
a]
þ13.9 (c 1.40, CHCl3); mp 148.3e149.7 ꢀC; the ee was de-
4.5.9. Compound 3i. Light yellow solid, 93% yield; 87:13 dr, 94% ee;
D
20
termined by HPLC (Chiralpak AD-H, EtOH/hexane¼30:70, flow rate
[a
]
ꢁ20.1 (c 1.10, CHCl3); mp 142.1e143.2 ꢀC; the ee was de-
D
1.0 mL/min,
l¼254 nm, major diastereomer: tminor¼15.2 min,
termined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
tmajor¼8.3 min); 1H NMR (300 MHz, CDCl3)
d
(major) 1.05 (t,
rate 1.0 mL/min,
l¼254 nm, major diastereomer: tminor¼55.2 min,
J¼6.9 Hz, 3H), 2.63 (s, 3H), 3.45e3.52 (m, 1H), 3.77e3.84 (m, 1H),
4.76 (s, 1H), 5.82 (s, 2H), 6.38e6.51 (m, 3H), 6.77 (d, J¼7.8 Hz, 1H),
7.15e7.19 (m, 2H), 7.30e7.39 (m, 3H), 7.68 (d, J¼7.2 Hz, 1H), 7.87 (d,
tmajor¼6.5 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.69 (s, 3H),
4.50 (d, J¼15.9 Hz, 1H), 4.97 (s, 1H), 5.11 (d, J¼15.9 Hz, 1H), 6.62 (d,
J¼7.5 Hz,1H), 6.81 (d, J¼6.6 Hz, 2H), 6.97 (d, J¼7.5 Hz, 2H), 7.11e7.23
(m, 9H), 7.34e7.40 (m, 2H), 7.74 (d, J¼7.2 Hz, 1H), 7.89 (d, J¼8.1 Hz,
J¼7.8 Hz, 2H), 8.70 (s, 1H); 13C NMR (75 MHz, CDCl3)
d (major) 12.1,
17.0, 35.2, 62.2, 73.7, 77.6, 101.2, 108.4, 108.9, 119.0, 122.3, 123.7,
124.0, 124.5, 125.4, 126.4, 128.8, 131.3, 137.5, 142.2, 147.9, 158.5,
2H), 8.77 (s, 1H); 13C NMR (75 MHz, CDCl3)
d (major) 17.1, 44.4, 62.1,
73.8, 77.5, 110.0, 119.1, 124.2, 124.5, 125.4, 126.3, 126.6, 126.9, 127.6,
127.7, 128.4, 128.5, 128.6, 128.7, 128.8, 129.0, 130.0, 130.5, 131.3,
171.2, 172.9, 198.0; IR (KBr):
n 3243, 2926, 1723, 1612, 1596, 1492,
1366, 1258, 1239, 1106, 1040, 755, 691 cmꢁ1; HRMS (ESI): Calcu-
134.3, 137.6, 142.5, 158.6, 171.2, 173.2, 198.0; IR (KBr): n 3245, 2925,
lated for C29H24N4NaO4S [MþNa]þ: 547.1410, found: 547.1417.
1724, 1613, 1595, 1497, 1363, 1178, 1158, 1130, 1078, 754, 693 cmꢁ1
;
HRMS (ESI): Calculated for C33H26N4NaO2S [MþNa]þ: 565.1669,
20
4.5.6. Compound 3f. White solid, 94% yield; 87:13 dr, 76% ee; [
a
]
found: 565.1658.
D
þ14.7 (c 1.08, CHCl3); mp 145.3e146.8 ꢀC; the ee was determined
by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow rate 1.0 mL/
4.5.10. Compound 3j. Light yellow solid, 96% yield; 86:14 dr, 87%
20
min,
l
¼254 nm, major diastereomer: tminor¼13.7 min,
ee; [
a]
ꢁ28.6 (c 1.04, CHCl3); mp 148.3e149.5 ꢀC; the ee was
D
tmajor¼5.0 min); 1H NMR (300 MHz, CDCl3)
d
(major) 1.07 (t,
determined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
J¼7.2 Hz, 3H), 2.58 (s, 3H), 3.45e3.54 (m, 1H), 3.81e3.88 (m, 1H),
4.83 (s, 1H), 6.80e6.86 (m, 2H), 6.97e7.00 (m, 1H), 7.07 (s, 1H),
7.17e7.22 (m, 2H), 7.29e7.32 (m, 1H), 7.36e7.41 (m, 3H), 7.70 (d,
J¼7.2 Hz, 1H), 7.87 (d, J¼7.8 Hz, 2H), 8.76 (s, 1H); 13C NMR (75 MHz,
rate 1.0 mL/min,
l
¼254 nm, major diastereomer: tminor¼23.3 min,
tmajor¼6.0 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.25 (s, 3H),
2.71 (s, 3H), 4.49 (d, J¼15.9 Hz, 1H), 4.92 (s, 1H), 5.12 (d, J¼15.9 Hz,
1H), 6.58 (d, J¼7.5 Hz,1H), 6.80 (d, J¼7.2 Hz, 2H), 6.87e6.93 (m, 4H),
7.13e7.23 (m, 6H), 7.34e7.39 (m, 2H), 7.73 (d, J¼6.9 Hz, 1H), 7.88 (d,
CDCl3)
d (major) 12.2, 17.0, 35.3, 60.6, 73.3, 77.1, 109.1, 119.2, 122.8,
124.2, 124.6, 125.6, 126.0, 126.7, 128.8, 130.4, 130.7, 131.5, 131.7,
133.0, 137.4, 142.2, 158.4, 171.0, 172.5, 197.5; IR (KBr): 3240, 2977,
J¼8.1 Hz, 2H), 8.81 (s, 1H); 13C NMR (75 MHz, CDCl3)
d (major) 17.1,
n
21.0, 44.3, 62.2, 73.9, 77.6, 109.9, 119.0, 124.1, 124.5, 125.3, 126.3,

1900
B.-D. Cui et al. / Tetrahedron 70 (2014) 1895e1902
126.5, 126.8, 127.2, 127.6, 128.4, 128.5, 128.6, 128.7, 129.2, 129.7,
131.1, 134.3, 137.5, 138.5, 142.4, 158.6, 171.2, 173.3, 198.2; IR (KBr):
3228, 2923, 1724, 1613, 1596, 1497, 1468, 1366, 1158, 1126, 755, 732,
130.0, 131.4, 134.2, 135.0, 137.4, 142.5, 158.2, 171.0, 173.0, 197.9; IR
(KBr): 3338, 2924, 1721, 1613, 1598, 1496, 1469, 1366, 1159, 1123,
n
n
1096, 1015, 754, 690 cmꢁ1
; HRMS (ESI): Calculated for
691, 667 cmꢁ1
;
HRMS (ESI): Calculated for C34H28N4NaO2S
C
33H25ClN4NaO2S [MþNa]þ: 599.1279, found: 599.1269.
[MþNa]þ: 579.1825, found: 579.1807.
4.5.15. Compound 3o. White solid, 90% yield; 63:37 dr, 89%, 91% ee;
20
20
4.5.11. Compound 3k. White solid, 95% yield; 83:17 dr, 88% ee; [
a
]
[a
]
þ50.9 (c 1.00, CHCl3); mp 209.6e210.8 ꢀC; the ee was de-
D
D
ꢁ26.4 (c 0.80, CHCl3); mp 123.6e124.8 ꢀC; the ee was determined
by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow rate 1.0 mL/
termined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
rate 1.0 mL/min,
l
¼254 nm, major diastereomer: tminor¼25.6 min,
min,
l
¼254 nm, major diastereomer: tminor¼17.8 min,
tmajor¼7.4
min; minor diastereomer: tminor¼18.9 min,
tmajor¼6.9 min); 1H NMR (300 MHz, CDCl3)
d
(major) 2.70 (s, 3H),
tmajor¼11.5 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.56 (s, 3H),
3.48 (s, 3H), 4.50 (d, J¼15.9 Hz, 1H), 4.94 (s, 1H), 5.11 (d, J¼15.9 Hz,
1H), 6.50 (s, 1H), 6.54e6.61 (m, 2H), 6.77e6.84 (m, 3H), 6.98e7.01
(m, 1H), 7.17e7.24 (m, 6H), 7.35e7.40 (m, 2H), 7.74 (d, J¼7.2 Hz, 1H),
7.89 (d, J¼7.8 Hz, 2H), 8.84 (s, 1H); 13C NMR (75 MHz, CDCl3)
4.50 (d, J¼15.9 Hz, 1H), 5.17 (d, J¼15.9 Hz, 1H), 5.68 (s, 1H),
6.50e6.52 (m, 1H), 6.88e6.97 (m, 4H), 7.16e7.21 (m, 6H), 7.34e7.39
(m, 2H), 7.47 (d, J¼7.8 Hz, 1H), 7.61 (d, J¼7.8 Hz, 1H), 7.73 (d,
J¼7.8 Hz, 2H), 8.37 (s, 1H), 8.69e8.72 (m, 1H); 13C NMR (75 MHz,
d
(major) 17.1, 44.4, 55.0, 62.0, 73.8, 77.4, 110.0, 113.4, 114.8, 119.1,
CDCl3) d (major) 14.6, 44.3, 53.2, 68.1, 73.9, 109.6, 119.7, 123.4, 124.7,
120.4, 124.2, 124.5, 125.4, 126.3, 126.6, 126.8, 127.7, 128.8, 130.0,
130.8,131.3, 131.8, 134.3,137.5, 142.6,158.7,159.7, 171.2, 173.2,198.0;
125.7, 126.6, 126.7, 127.1, 127.7, 128.7, 128.8, 129.1, 129.2, 130.3, 130.9,
132.6, 132.9, 134.3, 137.2, 142.4, 158.6, 169.0, 174.7, 197.0; IR (KBr):
n
IR (KBr):
n
3226, 2927, 1718, 1612, 1596, 1485, 1365, 1162, 1131, 1034,
3336, 2924, 1721, 1613, 1596, 1498, 1469, 1368, 1296, 1158, 1128,
1028, 755, 693 cmꢁ1; HRMS (ESI): Calculated for C33H25BrN4NaO2S
[MþNa]þ: 643.0774, found: 643.0799.
750, 730, 689, cmꢁ1; HRMS (ESI): Calculated for C34H28N4NaO3S
[MþNa]þ: 595.1774, found: 595.1786.
20
4.5.12. Compound 3l. White solid, 94% yield; 82:18 dr, 91% ee; [
a
]
4.5.16. Compound 3p. White solid, 95% yield; 83:17 dr, 80% ee;
D
20
ꢁ19.5 (c 1.04, CHCl3); mp 156.3e157.5 ꢀC; the ee was determined by
HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow rate 1.0 mL/
[a
]
ꢁ20.3 (c 1.00, CHCl3); mp 139.5e140.7 ꢀC; the ee was de-
D
termined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
min,
l
¼254 nm, major diastereomer: tminor¼29.5 min,
rate 1.0 mL/min,
l
¼254 nm, major diastereomer: tminor¼23.1 min,
tmajor¼8.4 min); 1H NMR (300 MHz, CDCl3)
d
(major) 2.74 (s, 3H),
tmajor¼6.3 min); 1H NMR (300 MHz, CDCl3):
d (major) 2.71 (s, 3H),
3.69 (s, 3H), 4.45 (d, J¼15.9 Hz, 1H), 4.88 (s, 1H), 5.12 (d, J¼15.9 Hz,
1H), 6.55e6.63 (m, 3H), 6.73 (d, J¼6.9 Hz, 2H), 6.91 (d, J¼8.7 Hz,
2H), 7.15e7.24 (m, 6H), 7.34e7.39 (m, 2H), 7.72e7.76 (m, 1H),
4.46 (d, J¼15.9 Hz, 1H), 4.86 (s, 1H), 5.11 (d, J¼15.9 Hz, 1H), 6.63 (d,
J¼7.5 Hz, 1H), 6.76e6.78 (m, 2H), 6.84 (d, J¼8.4 Hz, 2H), 7.19e7.24
(m, 8H), 7.35e7.40 (m, 2H), 7.72e7.75 (m, 1H), 7.86 (d, J¼7.8 Hz, 2H),
7.86e7.89 (m, 2H), 8.61 (s, 1H); 13C NMR (75 MHz, CDCl3)
d
(major)
8.76 (s, 1H); 13C NMR (75 MHz, CDCl3)
d (major) 17.1, 44.4, 61.9, 73.7,
17.1, 44.3, 55.1, 62.4, 74.0, 77.6, 109.9, 114.4, 119.1, 122.1, 124.2, 124.4,
125.3, 126.4, 126.6, 126.8, 127.7, 128.6, 128.7, 130.0, 131.2, 131.3,
77.2, 110.0. 119.1, 123.2, 124.3, 124.5, 125.5, 126.0, 126.8, 127.9, 128.7,
128.8,128.9,129.4,130.3,131.4,131.6,131.7,132.2,134.2,137.4,142.5,
134.3, 137.6, 142.5, 158.5, 159.8, 171.3, 173.3, 198.4; IR (KBr):
n
3244,
158.2, 171.0, 173.0, 197.8; IR (KBr): n 3335, 2925, 1721, 1613, 1596,
2928, 1724, 1612, 1596, 1516, 1488, 1364, 1255, 1181, 1119, 1031, 754,
691 cmꢁ1; HRMS (ESI): Calculated for C34H28N4NaO3S [MþNa]þ:
595.1774, found: 595.1788.
1491, 1468, 1366, 1158, 1128, 1079, 1011, 753, 692 cmꢁ1; HRMS (ESI):
Calculated for
643.0749.
C
33H25BrN4NaO2S [MþNa]þ: 643.0774, found:
4.5.13. Compound 3m. White solid, 95% yield; 77:23 dr, 94% ee;
4.5.17. Compound 3q. White solid, 95% yield; 56:44 dr, 87%, 82% ee;
20
20
[
a]
þ34.8 (c 0.80, CHCl3); mp 231.2e232.5 ꢀC; the ee was de-
[a
]
þ66.8 (c 0.55, CHCl3); mp 141.7e142.9 ꢀC; the ee was de-
D
D
termined by HPLC (Chiralpak AD-H, EtOH/hexane¼30:70, flow rate
termined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
1.0 mL/min,
l
¼254 nm, major diastereomer: tminor¼16.7 min,
rate 1.0 mL/min,
l
¼254 nm, major diastereomer: tminor¼24.4 min,
tmajor¼11.2 min); 1H NMR (300 MHz, CDCl3)
d
(major) 2.41 (s, 3H),
tmajor¼8.1 min; minor diastereomer: tminor¼10.0 min,
3.23 (s, 3H), 3.68 (s, 3H), 4.61 (d, J¼15.6 Hz, 1H), 5.18 (d, J¼15.6 Hz,
1H), 5.37 (s, 1H), 6.10e6.13 (m, 1H), 6.17 (d, J¼2.4 Hz, 1H), 6.69 (d,
J¼7.8 Hz, 1H), 7.01e7.04 (m, 2H), 7.12e7.25 (m, 7H), 7.35e7.40 (m,
2H), 7.73e7.75 (m, 1H), 7.94e7.97 (m, 2H), 8.48 (s, 1H); 13C NMR
tmajor¼8.8 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.39 (s, 3H),
4.70 (d, J¼15.6 Hz, 1H), 4.92 (s, 1H), 5.17 (d, J¼15.6 Hz, 1H), 5.73 (d,
J¼3.3 Hz, 1H), 5.97e5.98 (m, 1H), 6.68 (d, J¼7.8 Hz, 1H), 7.00 (s, 1H),
7.09e7.14 (m, 1H), 7.18e7.29 (m, 7H), 7.38e7.43 (m, 2H), 7.83e7.86
(m, 2H), 8.37 (br s, 1H), 8.55 (d, J¼7.5 Hz, 1H); 13C NMR (75 MHz,
(75 MHz, CDCl3)
d (major) 16.7, 44.4, 52.8, 55.0, 55.1, 73.0, 98.4,
103.9,109.6,111.8,118.5,123.9,124.8,125.1,126.2,126.3,127.3,127.5,
127.8, 128.6, 128.7, 128.8, 128.9, 130.9, 131.8, 134.5, 138.0, 142.6,
CDCl3) d (major) 13.6, 44.5, 49.5, 72.5, 75.0, 109.5,110.6, 119.5, 123.8,
124.6, 125.6, 127.1, 127.9, 128.8, 128.9, 129.0, 130.8, 134.6, 137.5,
142.3, 144.9, 158.0, 168.6, 174.5, 195.7; IR (KBr): 3212, 2923, 1724,
158.4, 158.7, 160.6, 172.1, 174.1, 198.7; IR (KBr):
n
3255, 2937, 1721,
n
1613, 1597, 1499, 1468, 1364, 1299, 1210, 1159, 1121, 1032, 754,
692 cmꢁ1; HRMS (ESI): Calculated for C35H30N4NaO4S [MþNa]þ:
625.1880, found: 625.1897.
1613, 1596, 1498, 1469, 1365, 1317, 1157, 1125, 1020, 755, 690 cmꢁ1
;
HRMS (ESI): Calculated for C31H24N4NaO3S [MþNa]þ: 555.1461,
found: 555.1467.
20
4.5.14. Compound 3n. White solid, 94% yield; 81:19 dr, 95% ee;
4.5.18. Compound 3r. White solid, 96% yield; 86:14 dr, 85% ee; [a]
D
20
[
a]
ꢁ35.1 (c 0.70, CHCl3); mp 139.0e140.3 ꢀC; the ee was de-
ꢁ3.9 (c 1.00, CHCl3); mp 118.5e119.8 ꢀC; the ee was determined by
HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow rate 1.0 mL/
D
termined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
rate 1.0 mL/min,
l
¼254 nm, major diastereomer: tminor¼21.6 min,
min,
l
¼254 nm, major diastereomer: tminor¼39.3 min,
tmajor¼6.4 min); 1H NMR (300 MHz, CDCl3)
d
(major) 2.71 (s, 3H),
tmajor¼7.8 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.71 (s, 3H),
4.46 (d, J¼15.9 Hz, 1H), 4.89 (s, 1H), 5.10 (d, J¼15.9 Hz, 1H), 6.63 (d,
J¼7.5 Hz, 1H), 6.76e6.78 (m, 2H), 6.90 (d, J¼8.4 Hz, 2H), 7.07 (d,
J¼8.4 Hz, 2H), 7.19e7.25 (m, 6H), 7.35e7.40 (m, 2H), 7.73 (d,
J¼6.6 Hz, 1H), 7.86 (d, J¼7.8 Hz, 2H), 8.74 (s, 1H); 13C NMR (75 MHz,
4.59 (d, J¼15.9 Hz, 1H), 5.04 (d, J¼15.9 Hz, 1H), 5.17 (s, 1H), 6.62 (d,
J¼7.8 Hz, 1H), 6.71 (d, J¼3.3 Hz, 1H), 6.76e6.80 (m, 1H), 6.86e6.88
(m, 2H), 7.10e7.12 (m, 1H), 7.18e7.29 (m, 6H), 7.36e7.41 (m, 2H),
7.70 (d, J¼7.2 Hz, 1H), 7.89e7.92 (m, 2H), 8.79 (s, 1H); 13C NMR
CDCl3)
d
(major) 17.1, 44.4, 61.8, 73.8, 77.3, 110.0. 119.1, 124.3, 124.5,
(75 MHz, CDCl3) d (major) 17.2, 44.4, 57.4, 73.8, 77.4, 110.0, 119.1,
125.5, 126.0, 126.8, 127.8, 127.9, 128.7, 128.8, 128.9, 129.0, 129.3,
124.2, 124.5, 125.4, 125.8, 126.4, 126.9, 127.1, 127.7, 127.9, 128.7,

B.-D. Cui et al. / Tetrahedron 70 (2014) 1895e1902
1901
128.8, 131.2, 131.4, 134.3, 137.5, 142.8, 158.4, 170.9, 172.9, 197.6; IR
min,
l
¼254 nm, major diastereomer: tminor¼7.3 min,
(KBr):
n
3336, 2924, 1721, 1613, 1596, 1497, 1469, 1364, 1316, 1156,
tmajor¼5.0 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.28 (s, 3H),
1125, 753, 698 cmꢁ1; HRMS (ESI): Calculated for C31H24N4NaO2S2
2.56 (s, 3H), 4.52 (d, J¼15.9 Hz, 1H), 4.74 (s, 1H), 5.08 (d, J¼15.9 Hz,
1H), 6.63 (d, J¼7.8 Hz,1H), 6.82e6.85 (m, 3H), 6.95 (d, J¼8.1 Hz, 2H),
7.15e7.27 (m, 6H), 7.64 (d, J¼7.2 Hz, 1H), 8.66 (br s, 1H); 13C NMR
[MþNa]þ: 571.1233, found: 571.1216.
4.5.19. Compound 3s. Light yellow solid, 95% yield; 88:12 dr, 93%
(75 MHz, CDCl3) d (major) 15.0, 21.0, 44.4, 62.4, 73.9, 74.1, 110.2,
20
ee; [
a
]
D
ꢁ38.4 (c 1.26, CHCl3); mp 119.7e121.3 ꢀC; the ee was de-
124.3, 124.4, 125.4, 126.0, 126.9, 127.8, 128.3, 128.7, 128.9, 129.3,
130.0, 131.6, 134.1, 139.2, 142.5, 165.0, 172.9, 176.5, 195.6; IR (KBr):
3332, 2923, 1790, 1727, 1613, 1488, 1469, 1369, 1179, 1116, 1080,
termined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
n
rate 1.0 mL/min,
l
¼254 nm, major diastereomer: tminor¼20.8 min,
tmajor¼5.0 min); 1H NMR (300 MHz, CDCl3)
d
(major) 2.35 (s, 3H),
1013, 877, 752, 696 cmꢁ1
;
HRMS (ESI): Calculated for
2.67 (s, 3H), 4.49 (d, J¼15.9 Hz, 1H), 4.97 (s, 1H), 5.09 (d, J¼15.9 Hz,
1H), 6.50 (d, J¼7.8 Hz, 1H), 6.81 (d, J¼6.3 Hz, 2H), 6.97 (d, J¼7.5 Hz,
2H), 7.03e7.23 (m, 8H), 7.36e7.41 (m, 2H), 7.55 (s, 1H), 7.92 (d,
C
28H23N3NaO3S [MþNa]þ: 504.1352, found: 504.1350.
20
4.5.24. Compound 6d. Yellow solid, 94% yield; 92:8 dr, 73% ee; [a]
D
J¼7.8 Hz, 2H), 8.74 (s, 1H); 13C NMR (75 MHz, CDCl3)
d
(major) 17.0,
ꢁ38.4 (c 1.13, CHCl3); mp 108.5e109.8 ꢀC; the ee was determined by
HPLC (Chiralpak OD-H, i-PrOH/hexane¼10:90, flow rate 1.0 mL/
21.0, 44.4, 61.8, 73.8, 77.5, 109.8, 119.1, 125.1, 125.4, 126.2, 126.9,
127.6, 128.3, 128.5, 128.6, 128.7, 128.8, 129.0, 130.0, 130.7, 131.6,
min,
l¼254 nm, major diastereomer: tminor¼15.1 min,
134.2, 134.4, 137.6, 140.1, 158.7, 171.3, 173.2, 197.9; IR (KBr):
n
3255,
tmajor¼19.8 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.60 (s, 3H),
2923, 2854, 1715, 1613, 1597, 1499, 1363, 1178, 1131, 818, 751, 696,
595 cmꢁ1; HRMS (ESI): Calculated for C34H28N4NaO2S [MþNa]þ:
579.1825, found: 579.1828.
3.72 (s, 3H), 4.48 (d, J¼15.9 Hz, 1H), 4.71 (s, 1H), 5.08 (d, J¼15.9 Hz,
1H), 6.60e6.66 (m, 3H), 6.77 (d, J¼7.2 Hz, 2H), 6.87 (d, J¼8.7 Hz,
2H), 7.13e7.27 (m, 5H), 7.63 (d, J¼7.2 Hz, 1H), 8.63 (s, 1H); 13C NMR
(75 MHz, CDCl3)
d (major) 15.0, 44.3, 55.1, 62.6, 74.0, 74.2, 110.1,
4.5.20. Compound 3t. White solid, 98% yield; >99:1 dr, 2% ee; mp
215.8e217.2 ꢀC; the ee was determined by HPLC (Chiralpak AD-H, i-
114.6,114.7,120.7,124.2,124.3,125.4,126.8,127.8,128.7,129.9,131.5,
134.1, 137.0, 142.5, 149.6, 160.1, 165.0, 172.9, 176.5, 195.7; IR (KBr):
n
PrOH/hexane¼30:70, flow rate 1.0 mL/min,
l
¼254 nm,
3249, 2926, 1790, 1727, 1612, 1587, 1516, 1488, 1469, 1369, 1257,
tminor¼9.6 min, tmajor¼7.2 min); 1H NMR (300 MHz, DMSO-d6)
1181, 1119, 1030, 878, 754, 699 cmꢁ1; HRMS (ESI): Calculated for
d
1.02 (s, 3H), 1.32 (s, 3H), 2.35 (s, 3H), 3.13 (s, 3H), 7.06e7.25 (m,
C
28H23N3NaO4S [MþNa]þ: 520.1301, found: 520.1296.
3H), 7.38e7.47 (m, 3H), 7.77e7.85 (m, 3H), 11.21 (s, 1H); 13C NMR
(75 MHz, DMSO-d6) 18.1, 26.4, 26.6, 26.7, 48.2, 77.7, 80.4, 109.1,
118.6, 122.3, 125.3, 125.8, 127.1, 129.0, 130.4, 137.1, 143.7, 158.7, 170.2,
174.4, 196.5; IR (KBr): 3125, 3055, 2975, 1728, 1615, 1532, 1490,
20
d
4.5.25. Compound 6e. White solid, 94% yield; 92:8 dr, 67% ee; [a]
D
ꢁ26.8 (c 1.00, CHCl3); mp 192.5e193.8 ꢀC; the ee was determined
by HPLC (Chiralpak OD-H, i-PrOH/hexane¼10:90, flow rate 1.0 mL/
n
1471, 1371, 1352, 1273, 1186, 1152, 1113, 1088, 1047, 761, 752,
690 cmꢁ1; HRMS (ESI): Calculated for C23H22N4NaO2S [MþNa]þ:
441.1356, found: 441.1356.
min,
l
¼254 nm, major diastereomer: tminor¼13.0 min,
tmajor¼18.1 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.59 (s, 3H),
4.51 (d, J¼15.9 Hz, 1H), 4.73 (s, 1H), 5.06 (d, J¼15.9 Hz, 1H), 6.67 (d,
J¼7.8 Hz, 1H), 6.80e6.85 (m, 3H), 6.90e6.93 (m, 2H), 7.17e7.31 (m,
6H), 7.65 (d, J¼7.2 Hz, 1H), 8.63 (br s, 1H); 13C NMR (75 MHz, CDCl3)
20
4.5.21. Compound 6a. White solid, 95% yield; 90:10 dr, 74% ee; [a]
D
ꢁ1.1 (c 1.10, CHCl3); mp 110.2e111.7 ꢀC; the ee was determined by
HPLC (Chiralpak AS-H, i-PrOH/hexane¼50:50, flow rate 1.0 mL/min,
d
(major) 14.9, 44.4, 62.1, 73.8, 74.0, 110.2, 116.4 (d, J¼21.5 Hz, 1C),
124.3, 124.4, 125.2, 126.7, 126.9, 128.0, 128.7, 128.8, 128.9, 130.5 (d,
l
¼254 nm, major diastereomer: tminor¼39.2 min, tmajor¼13.3 min);
J¼8.3 Hz, 1C), 131.8, 134.1, 136.7, 142.5, 148.4, 163.1 (d, J¼250.1 Hz,
1H NMR (300 MHz, CDCl3)
d
(major) 2.43 (s, 3H), 3.13 (s, 3H), 4.75 (s,
1C), 164.7, 172.7, 176.3, 195.3; IR (KBr): n 3198, 3063, 2922, 1794,
1H), 6.81 (d, J¼7.8 Hz, 1H), 6.92 (d, J¼7.2 Hz, 2H), 7.08e7.23 (m, 4H),
1732,1612,1512,1490,1470,1366,1237,1202,1163,1126,1105,1080,
7.35e7.43 (m, 1H), 7.63 (d, J¼7.2 Hz, 1H), 8.56 (br s, 1H); 13C NMR
1013, 880, 753, 698 cmꢁ1
;
HRMS (ESI): Calculated for
(75 MHz, CDCl3)
d
(major) 14.8, 26.7, 61.5, 73.5, 74.1, 109.3, 124.2,
C
27H20FN3NaO3S [MþNa]þ: 508.1102, found: 508.1094.
124.4, 125.3, 127.7, 128.8, 129.0, 129.2, 129.4, 129.5, 131.7, 143.1,
164.9, 172.9, 176.5, 195.3; IR (KBr): 3205, 2937, 1787, 1728, 1613,
n
4.5.26. Compound 6f. Light yellow solid, 92% yield; 89:11 dr, 68%
20
1506, 1376, 1353, 1197, 1157, 1101, 875, 750, 699 cmꢁ1; HRMS (ESI):
ee; [a
]
ꢁ1.9 (c 1.20, CHCl3); mp 158.7e160.2 ꢀC; the ee was de-
D
Calculated for
414.0883.
C
21H17N3NaO3S [MþNa]þ: 414.0883, found:
termined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
rate 1.0 mL/min,
l¼254 nm, major diastereomer: tminor¼10.4 min,
tmajor¼6.4 min); 1H NMR (300 MHz, CDCl3)
d (major) 2.61 (s, 3H),
20
4.5.22. Compound 6b. White solid, 96% yield; 94:6 dr, 77% ee; [
a
]
4.61 (d, J¼15.9 Hz, 1H), 4.95 (d, J¼15.9 Hz, 1H), 5.03 (s, 1H), 6.67 (d,
J¼7.8 Hz, 1H), 6.72 (d, J¼3.0 Hz, 1H), 6.80e6.90 (m, 3H), 7.17e7.31
(m, 6H), 7.64 (d, J¼7.5 Hz, 1H), 8.40 (s, 1H); 13C NMR (75 MHz,
D
ꢁ18.6 (c 1.10, CHCl3); mp 110.5e111.9 ꢀC; the ee was determined by
HPLC (Chiralpak OD-H, i-PrOH/hexane¼10:90, flow rate 1.0 mL/
min,
l
¼254 nm, major diastereomer: tminor¼11.7 min,
CDCl3) d (major) 15.1, 44.4, 57.9, 73.8, 74.0, 110.2, 124.3, 124.4, 126.7,
tmajor¼16.6 min); 1H NMR (300 MHz, CDCl3)
d
(major) 2.56 (s, 3H),
127.0, 127.1, 127.3, 127.9, 128.6, 128.8,128.9, 129.2, 129.8,131.8, 134.1,
142.8, 164.7, 172.5, 176.2, 195.1; IR (KBr): 3106, 2954, 1793, 1713,
1614, 1498, 1433, 1378, 1331, 1304, 1199, 1158, 1125, 1084, 1015, 888,
4.53 (d, J¼15.9 Hz, 1H), 4.79 (s, 1H), 5.07 (d, J¼15.9 Hz, 1H), 6.65 (d,
J¼7.8 Hz, 1H), 6.84 (d, J¼6.9 Hz, 2H), 6.94 (d, J¼7.5 Hz, 2H),
7.09e7.31 (m, 8H), 7.65 (d, J¼6.9 Hz, 1H), 8.66 (br s, 1H); 13C NMR
n
756, 702 cmꢁ1
; HRMS (ESI): Calculated for C25H19N3NaO3S2
(75 MHz, CDCl3)
d
(major) 14.9, 44.4, 62.3, 73.8, 74.0, 110.2, 124.3,
[MþNa]þ: 496.0760, found: 496.0752.
124.4, 125.4, 126.9, 127.8, 128.3, 128.8, 128.9, 129.0, 129.2, 129.3,
129.7, 131.6, 134.1, 142.5, 164.9, 172.9, 176.4, 195.4; IR (KBr): 3317,
n
4.5.27. Compound 6g. Light yellow solid, 93% yield; 60:40 dr, 64%,
3062, 3032, 2926, 1790, 1728, 1613, 1487, 1469, 1367, 1178, 1120,
53% ee; [
a
]
20 ꢁ18.3 (c 1.00, CHCl3); mp 136.2e137.5 ꢀC; the ee was
D
1081, 1013, 877, 748, 697 cmꢁ1; HRMS (ESI): Calculated for
determined by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow
C
27H21N3NaO3S [MþNa]þ: 490.1196, found: 490.1195.
rate 1.0 mL/min,
l¼254 nm, minor diastereomer: tminor¼12.2 min,
tmajor¼19.6 min; major diastereomer: tminor¼10.4 min,
20
4.5.23. Compound 6c. White solid, 93% yield; 93:7 dr, 77% ee; [
a
]
tmajor¼5.7 min); 1H NMR (300 MHz, CDCl3)
d
(majorþminor) 2.36
D
ꢁ33.8 (c 0.40, CHCl3); mp 136.2e137.6 ꢀC; the ee was determined
by HPLC (Chiralpak AD-H, i-PrOH/hexane¼30:70, flow rate 1.0 mL/
(s, 2.2H), 2.74 (s, 0.8H), 4.28 (d, J¼15.9 Hz, 0.7H), 4.42 (d, J¼15.9 Hz,
0.3H), 4.99 (d, J¼15.9 Hz, 0.7H), 5.08 (d, J¼15.9 Hz, 0.3H), 5.79 (s,

1902
B.-D. Cui et al. / Tetrahedron 70 (2014) 1895e1902
1381e1407; (c) Hong, L.; Wang, R. Adv. Synth. Catal. 2013, 355, 1023e1052; (d)
Dalpozzo, R.; Bartolib, G.; Bencivenni, G. Chem. Soc. Rev. 2012, 41, 7247e7290;
(e) Singh, G. S.; Desta, Z. Y. Chem. Rev. 2012, 112, 6104e6155.
0.7H), 5.89 (s, 0.3H), 6.31e6.41 (m, 2.4H), 6.61 (d, J¼7.5 Hz, 0.6H),
6.72e6.77 (m, 1.4H), 6.96e7.01 (m, 0.6H), 7.07e7.38 (m, 4.3H),
7.48e7.59 (m, 2.3H), 7.66 (d, J¼8.4 Hz, 1H), 7.75e7.87 (m, 2H), 8.12
(d, J¼8.4 Hz, 0.7H), 8.46 (s, 0.3H), 8.53 (s, 0.7H), 8.61e8.64 (m,
4. For selected examples, see: (a) Tan, B.; Candeias, N. R.; Barbas, C. F., III. Nat.
Chem. 2011, 3, 473e477; (b) Sun, W.; Zhu, G.; Wu, C.; Hong, L.; Wang, R. Chem.
dEur. J. 2012, 18, 6737e6741; (c) Cao, Y. M.; Shen, F. F.; Zhang, F. T.; Wang, R.
Chem.dEur. J. 2013, 19, 1184e1188; (d) Chen, Q.; Liang, J.; Wang, S.; Wang, D.;
Wang, R. Chem. Commun. 2013, 1657e1659; (e) Wu, H.; Zhang, L. L.; Tian, Z. Q.;
Huang, Y. D.; Wang, Y. M. Chem.dEur. J. 2013, 19, 1747e1753; (f) Tan, F.; Cheng,
H.-G.; Feng, B.; Zou, Y.-Q.; Duan, S.-W.; Chen, J.-R.; Xiao, W.-J. Eur. J. Org. Chem.
2013, 2071e2075; (g) Han, W. Y.; Li, S. W.; Wu, Z. J.; Zhang, X. M.; Yuan, W. C.
Chem.dEur. J. 2013, 19, 5551e5556.
5. (a) Chen, W. B.; Wu, Z. J.; Hu, J.; Cun, L. F.; Zhang, X. M.; Yuan, W. C. Org. Lett.
2011, 13, 2472e2475; (b) Kato, S.; Kanai, M.; Matsunaga, S. Chem.dAsian J. 2013,
8, 1768e1771; (c) Chen, W. B.; Han, W. Y.; Han, Y. Y.; Zhang, X. M.; Yuan, W. C.
Tetrahedron 2013, 69, 5281e5286.
0.7H); 13C NMR (75 MHz, CDCl3)
d
(majorþminor) 12.5, 15.0, 44.3,
44.4, 48.9, 55.9, 74.3, 74.5, 74.7, 109.9, 110.2, 120.9, 121.7, 123.8,
124.2, 124.3, 124.5, 124.9, 125.0, 125.1, 125.3, 126.1, 126.2, 126.5,
127.1, 127.4, 127.5, 127.7, 127.8, 128.1, 128.5, 128.6, 128.8, 128.9, 129.0,
129.5,129.9,130.3,131.1,131.6,132.1,132.2,133.6,133.8,133.9,140.0,
142.2, 142.5, 164.6, 164.9, 173.6, 174.3, 174.4, 176.4, 194.9, 196.2; IR
(KBr):
n 3224, 3062, 2926, 1787, 1727, 1613, 1490, 1371, 1204, 1158,
1119, 1079, 1011, 877, 751, 697 cmꢁ1; HRMS (ESI): Calculated for
C
31H23N3NaO3S [MþNa]þ: 540.1352, found: 540.1350.
6. Han, Y. Y.; Chen, W. B.; Han, W. Y.; Wu, Z. J.; Zhang, X. M.; Yuan, W. C. Org. Lett.
2012, 14, 490e493.
7. Kato, S.; Yoshino, T.; Shibasaki, M.; Kanai, M.; Matsunaga, S. Angew. Chem., Int.
Ed. 2012, 51, 7007e7010.
4.5.28. Compound 7.4d White solid, 82% yield; >99:1 dr, 86% ee;
20
[
a
]
þ33.5 (c 1.00, CHCl3); the ee was determined by HPLC (Chir-
D
8. (a) Liu, X. L.; Han, W. Y.; Zhang, X. M.; Yuan, W. C. Org. Lett. 2013, 15, 1246e1249;
(b) Du, D.; Jiang, Y.; Xu, Q.; Shi, M. Adv. Synth. Catal. 2013, 355, 2249e2256.
9. For selected examples, see: (a) Bencivenni, G.; Wu, L.-Y.; Mazzanti, A.;
Giannichi, B.; Pesciaioli, F.; Song, M.-P.; Bartoli, G.; Melchiorre, P. Angew. Chem.,
Int. Ed. 2009, 48, 7200e7203; (b) Pesciaioli, F.; Righi, P.; Mazzanti, A.; Bartoli, G.;
Bencivenni, G. Chem.dEur. J. 2011, 17, 2842e2845; (c) Albertshofer, K.; Tan, B.;
Barbas, C. F., III. Org. Lett. 2012, 14, 1834e1837; (d) Dou, X.; Lu, Y. Chem.dEur. J.
2012, 18, 8315e8319; (e) Noole, A.; Sucman, N. S.; Kabeshov, M. A.; Kanger, T.;
Macaev, F. Z.; Malkov, A. V. Chem.dEur. J. 2012, 18, 14929e14933; (f)
Ramachary, D. B.; Venkaiah, C.; Madhavachary, R. Org. Lett. 2013, 15,
3042e3045; (g) Tian, X.; Melchiorre, P. Angew. Chem., Int. Ed. 2013, 52,
5360e5363.
alpak AD-H, i-PrOH/hexane¼40:60, flow rate 1.0 mL/min,
l
¼254 nm, tminor¼16.6 min, tmajor¼6.3 min); 1H NMR (300 MHz,
CDCl3)
d
2.52 (s, 3H), 2.64 (s, 3H), 4.60 (d, J¼15.9 Hz, 1H), 4.98 (s,
1H), 5.21 (d, J¼15.9 Hz, 1H), 6.72 (d, J¼7.5 Hz, 1H), 6.94 (d, J¼7.5 Hz,
2H), 7.00e7.03 (m, 2H), 7.09 (t, J¼7.5 Hz, 2H), 7.15e7.25 (m, 7H),
7.45 (t, J¼7.8 Hz, 2H), 7.64 (d, J¼6.9 Hz, 1H), 8.01 (d, J¼8.1 Hz, 2H).
Acknowledgements
10. (a) Liu, L.; Zhong, Y.; Zhang, P.; Jiang, X.; Wang, R. J. Org. Chem. 2012, 77,
10228e10234; (b) Liang, J.; Chen, Q.; Liu, L.; Jiang, X.; Wang, R. Org. Biomol.
Chem. 2013, 11, 1441e1445; (c) Geng, Z.-C.; Chen, X.; Zhang, J.-X.; Li, N.; Chen, J.;
Huang, X.-F.; Zhang, S.-Y.; Tao, J.-C.; Wang, X.-W. Eur. J. Org. Chem. 2013,
4738e4743.
We are grateful for financial support from the National Natural
Science Foundation of China (No. 21372217), the National Basic
Research Program of China (973 Program) (2010CB833300), and
Western Light Talent Culture Project, and Sichuan Youth Science
and Technology Foundation.
11. For selectedexamples of our group, see:(a) Chen, W. B.; Wu, Z. J.; Pei, Q. L.; Cun, L. F.;
Zhang, X. M.; Yuan, W. C. Org. Lett. 2010, 12, 3132e3135; (b) Han, Y. Y.; Han, W. Y.;
Hou, X.; Zhang, X. M.; Yuan, W. C. Org. Lett. 2012,14, 4054e4057; (c) Liao, Y. H.; Wu,
Z. J.; Han, W. Y.; Zhang, X. M.; Yuan, W. C. Chem.dEur. J. 2012, 18, 8916e8920; (d)
Liao, Y. H.; Liu, X. L.; Wu, Z. J.; Du, X. L.; Zhang, X. M.; Yuan, W. C. Chem.dEur. J. 2012,
18, 6679e6687; (e) Han, Y. Y.; Wu, Z. J.; Chen, W. B.; Du, X. L.; Zhang, X. M.; Yuan, W.
C. Org. Lett. 2011,13, 5064e5067; (f) Liu, X. L.; Wu, Z. J.; Du, X. L.; Zhang, X. M.; Yuan,
W. C. J. Org. Chem. 2011, 76, 4008e4017; (g) Liu, X. L.; Liao, Y. H.; Wu, Z. J.; Cun, L. F.;
Zhang, X. M.; Yuan, W. C. J. Org. Chem. 2010, 75, 4872e4875; (h) Liao, Y. H.; Liu, X. L.;
Wu, Z. J.; Cun, L. F.; Zhang, X. M.; Yuan, W. C. Org. Lett. 2010, 12, 2896e2899.
12. For a selected example about the reaction of unsaturated isoxazolones, see: Tu,
S.; Zhang, J.; Jia, R.; Jiang, B.; Zhang, Y.; Jiang, H. Org. Biomol. Chem. 2007, 5,
1450e1453.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.01.036.
References and notes
1. (a) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2209e2219; (b) Galliford, C. V.;
Scheidt, K. A. Angew. Chem., Int. Ed. 2007, 46, 8748e8758; (c) Greshock, T. J.;
Grubbs, A. W.; Jiao, P.; Wicklow, D. T.; Gloer, J. B.; Williams, R. M. Angew. Chem., Int.
Ed. 2008, 47, 3573e3577; (d) Mugishima, T.; Tsuda, M.; Kasai, Y.; Ishiyama, H.;
Fukushi, E.; Kawabata, J.; Watanabe, M.; Akao, K.; Kobayashi, J. I. J. Org. Chem.
2005, 70, 9430e9435; (e) Fensome, A.; Adams, W. R.; Adams, A. L.; Berrodin, T. J.;
Cohen, J.; Huselton, C.; Illenberger, A.; Kern, J. C.; Hudak, V. A.; Marella, M. A.;
Melenski, E. G.; McComas, C. C.; Mugford, C. A.; Slayden, O. D.; Yudt, M.; Zhang, Z.;
Zhang, P.; Zhu, Y.; Winneker, R. C.; Wrobel, J. E. J. Med. Chem. 2008, 51,1861e1873.
2. For selected examples, see: (a) Thayer, A. M. Chem. Eng. News 2007, 85, 11e19;
(b) Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2007, 70, 461e477.
13. For selected examples, see: (a) Li, L.; Klauber, E. G.; Seidel, D. J. Am. Chem. Soc.
2008, 130, 12248e12249; (b) Li, L.; Ganesh, M.; Seidel, D. J. Am. Chem. Soc. 2009,
131, 11648e11649; (c) Jiang, X.; Zhang, G.; Fu, D.; Cao, Y.; Shen, F.; Wang, R. Org.
Lett. 2010, 12, 1544e1547; (d) Vecchione, M. K.; Li, L.; Seidel, D. Chem. Commun.
2010, 4604e4606; (e) Jiang, X.; Cao, Y.; Wang, Y.; Liu, L.; Shen, F.; Wang, R. J. Am.
Chem. Soc. 2010, 132, 15328e15333; (f) Chen, X.; Dong, S.; Qiao, Z.; Zhu, Y.; Xie,
M.; Lin, L.; Liu, X.; Feng, X. Chem.dEur. J. 2011, 17, 2583e2586; (g) Tan, B.; Zeng,
X.; Leong, W. W. Y.; Shi, Z.; Barbas, C. F., III; Zhong, G. Chem.dEur. J. 2012, 18,
63e67; (h) Shi, Z.; Yu, P.; Chua, P. J.; Zhong, G. Adv. Synth. Catal. 2013, 355,
2797e2800.
3. For selected reviews, see: (a) Trost, B. M.; Brennan, M. K. Synthesis 2009,
3003e3025; (b) Zhou, F.; Liu, Y. L.; Zhou, J. Adv. Synth. Catal. 2010, 352,