Enantioselective cascade reactions of stable sulfur ylides and nitroolefins through an axial-to-central chirality transfer strategy

Article abstract of DOI:10.1021/jo202324f

An enantioselective [4 + 1] annulation/rearrangement cascade of stable sulfur ylides and nitroolefins has been developed through an efficient axial-to-central chirality transfer with the use of a chiral BINOL-derived sulfide as a reliable stereocontroller

Full text of DOI:10.1021/jo202324f

Article
pubs.acs.org/joc
Enantioselective Cascade Reactions of Stable Sulfur Ylides and
Nitroolefins through an Axial-to-Central Chirality Transfer Strategy
Liang-Qiu Lu, Zhi-Hui Ming, Jing An, Chao Li, Jia-Rong Chen, and Wen-Jing Xiao*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152
Luoyu Road, Wuhan, Hubei 430079, China
S
* Supporting Information
ABSTRACT: An enantioselective [4 + 1] annulation/
rearrangement cascade of stable sulfur ylides and nitroolefins
has been developed through an efficient axial-to-central
chirality transfer with the use of a chiral BINOL-derived
sulfide as a reliable stereocontroller. It can provide
pharmaceutically and synthetically important oxazolidinones
in high stereoselectivities (up to 96:4 e.r. and >95:5 d.r.).
Moreover, this strategy was also successfully applied to the asymmetric [4 + 1]/[3 + 2] cycloaddition cascade of sulfur ylides with
alkene-tethered nitroolefins, and the corresponding enantioenriched fused heterocycles (up to 87:13 e.r. and >95:5 d.r.) were
obtained in good to excellent yields (54−95% yields).
hand, over the past decades, another strategy, “axial-to-central
chirality transfer”, has proven to be another important proto-
col for promoting the evolvement of asymmetric synthesis.17
Nevertheless, it still remains a limited application in the trans-
formation of sulfur ylides. To the best of our knowledge, there
are only two reports primarily disclosed by Seki et al18a and
Uemura et al18b before our work, wherein axial chiral sulfides 1
and 219 (Scheme 2) were applied to the asymmetric epoxi-
dation reaction of aromatic aldehydes (eqs 1 and 2, Scheme 2).
Though they did not unequivocally demonstrate the idea that
axial-to-central chirality transfer can indeed efficiently promote
the asymmetric epoxidation of semistable sulfur ylides with
excellent enantioselectivities, these achievements paved the way
for the development of formal [4 + 1] annulations of stable
sulfur ylides with conjugated systems, which would provide an
efficient approach to highly enantiomerically enriched five-
membered heterocycles.
Recently, we first applied the axial-to-central chirality transfer
strategy to the asymmetric [4 + 1] pyrroline annulation of
unsaturated imines with stable sulfur ylides, and excellent
asymmetric induction was observed (eq 3, Scheme 2, up to
99:1 e.r.).20 Inspired by this success, we envisaged that the
axially chiral sulfide 2 might be further utilized in other
enantioselective reactions. Herein, we describe two types of
asymmetric cascade reactions of stable sulfur ylides with nitro-
olefins, giving optically active oxazolidinones and structurally
complex fused heterocycles in a concise fashion with moderate
to good chemo- and stereoselectivities (up to 71% yield, 96:4
e.r., and >95:5 d.r.; up to 95% yield, 87:13 e.r., and >95:5 d.r.),
respectively.
INTRODUCTION
■
Cascade reactions have been established as a powerful strategy
for the rapid construction of complex functional molecules.1 In
this context, sulfur ylides have provided excellent opportunities
for developing new cascade transformations.2,3 Impressively,
remarkable advances have been achieved with respect to
asymmetric cascade reactions involving sulfur ylides over the
past decade. For instance, elegant works from Borhan,4
Aggarwal,5 Tang,6 and many other groups7 have successfully
developed sulfoxonium ylides, vinyl sulfonium salts, and
crotonate-derived sulfonium salts as versatile reagents to
construct highly complex and optically active heterocyclic
compounds. Despite advances, cascade reactions employing
stable sulfur ylides as the reactant still remain a continuing
challenge due to their relatively low activity.8 In this regard, our
group has developed two types of cascade reactions of stable
sulfur ylides with highly electrophilic nitroolefins,9 which pro-
vided a powerful platform for the rapid and efficient assembly
of cheap and readily available starting materials into biologically
and synthetically significant oxazolidinones10 (Scheme 1, A)
and chroman-incorporated fused heterocycles11 (Scheme 1, B).
In view of their importance, considerable research efforts have
been directed toward the development of efficient methods for
their enantioselective synthesis.12
Sulfur ylide-participated asymmetric transformations mostly
involve the chiral sulfur ylide dictating the chirality of the
products, in which stereochemical information is transferred
from the chiral sulfide to the resulting chiral product.2,3b Such a
process is common in the asymmetric epoxidation, aziridina-
tion, and cyclopropanation,2 as well as other cascade reactions
to construct chiral dihydrofurans,13a cyclohexenes,6 and nitro-
nates.13b To the best of our knowledge, most of the enantio-
pure sulfides are derived from natural centrally chiral sources,
such as camphor,14 amino acids,15 and sugars.16 On the other
Received: November 16, 2011
Published: December 15, 2011
© 2011 American Chemical Society
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Scheme 1. Our Previous Works on the Cascade Reactions of Stable Sulfur Ylides with Nitroolefins
Scheme 2. Axially Chiral Sulfides
nitroolefin 4a afforded the corresponding oxazolidinone 5aa in
good yield (69%) with good enantioselectivity (85:15 e.r.)
upon treatment with 10 mol % 2-chlorophenyl thioures (2-
CTU) and 4-(dimethylamino)pyridine (DMAP) in dichloro-
methane at room temperature for 16 h (Table 1, entry 1).
Further examination of reaction media showed that this
asymmetric cascade reaction was remarkably influenced by
the polarity of solvents (Table 1, entries 1−8). The weak polar
solvents, such as toluene, have positively affected the
enantioselectivity (Table 1, entry 8, 35% yield and 90:10
e.r.), and the moderately polar dichloromethane was the best
solvent of choice in terms of reaction efficiency (Table 1, entry
1, 69% yield and 85:15 e.r.). Interestingly, we found that a
mixture of toluene and CH2Cl2 in a 4:1 ratio provided the
satisfactory results with 63% yield and 90:10 e.r. (Table 1, entry
9).21 Further optimization of reaction parameters, such as the
ratio of reagents (3a/4a), concentration, and temperature,
resulted in a higher yield and enantiomeric ratio of the desired
chiral oxazolidinone (Table 1, entry 13, 71% yield and 95:5 er).
When the reaction was conducted at −40 °C, the enantiomeric
RESULTS AND DISCUSSION
■
Despite the success of the enantioselective [4 + 1] pyrroline
annulation of α,β-unsaturated imines with chiral sulfur ylides 3,
there still exist two major challenges for the development of an
enantioselective [4 + 1] annulation/rearrangement cascade of
stable sulfur ylides and nitroolefins through an axial-to-central
chirality transfer strategy (Scheme 3): (1) in the cascade
reaction for oxazolidinone synthesis, the requisite combination
of multiple catalysts, such as thiourea and DMAP, together with
the following rearrangements made this asymmetric cascade
process formidable in terms of chemo- and enantioselectivity;
(2) unlike the asymmetric [4 + 1] annulation of unsaturated
imines where the protecting group on nitrogen functions as a
stereotunable effect, there is not a similar steric effect on the
nitroolefin to improve the stereodiscrimination.
Condition Optimization for the Enantioselective [4 +
1] Annulation/Rearrangement Cascade. With these
thoughts in mind, initial attempts for experimental validation
of the hypothesis were implemented using axially chiral sulfur
ylides to provide enantioenriched oxazolidinones (Table 1). To
our delight, the reaction of axially chiral sulfur ylide 3a with
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Scheme 3. Proposal and Challenge
a
Table 1. Condition Optimization for the Enantioselective Cascade [4 + 1] Annulation/Rearrangement Reaction
b
c
entry
solvent
CH2Cl2
concn (M)
time (h)
yield (%)
e.r. (%)
1
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.08
0.01
0.01
0.01
16
48
48
60
48
35
40
48
48
65
65
48
26
72
69
47
25
45
trace
43
53
35
63
59
68
52
71
41
85:15
87:13
82:18
85:15
2
3
4
5
6
7
CHCl3
Et2O
THF
d
DMF
n.d.
CH3CN
64:36
46:54
90:10
90:10
90:10
92:8
CH3OH
8
toluene
e
9
toluene/CH2Cl2
toluene/CH2Cl2
toluene/CH2Cl2
toluene/CH2Cl2
toluene/CH2Cl2
toluene/CH2Cl2
ef
,
10
eg
,
11
12
eg
,
95:5
eh
,
13
ehi
95:5
,
,
14
97:3
a
b
The reactions were carried out on a 0.2 mmol scale of 4a with 1.1 equiv of 3a at room temperature in the corresponding solvent. Isolated yield.
c
d
e
f
e.r. was determined by chiral stationary phase HPLC analysis. n.d. = not determined. The ratio of toluene and DCM is 4:1. The ratio of 3a/4a
g
h
i
was changed to 1:1. The ratio of 3a/4a was changed to 1:1.5. The ratio of 3a/4a was changed to 1.25:1. The reaction was carried out at −40 °C.
ratio could be improved to 97:3, albeit with a lowered yield
(Table 1, entry 14).
enantiomeric ratios are obtained (Scheme 4, 5ag: 68% yield,
>95:5 d.r., and 95:5 e.r.). In the cases of 2-methoxyl-β-
nitrostyrene and α-naphthyl nitroolefin, the asymmetric cascade
reactions also gave corresponding products, though the
decrease in enantiomeric excess was observed because of the
possible steric repulsion (Scheme 4, 5ah: 65% yield, >95:5 d.r.,
88:12 e.r.; 5ai: 58% yield, >95:5 d.r., 92:8 e.r.). Notably,
multiple substituted 3,4-difluoro-β-nitrostyrene was also
successfully utilized to prepare chiral oxazolidinone conven-
iently in moderate yield with good stereoselectivity (Scheme 4,
5aj: 50% yield, >95:5 d.r., 92:8 e.r.), which is an important
intermediate to access a potential alpha adrenergic receptor
antagonist.22 Finally, aliphatic nitroolefins, such as isopropyl
nitroolefin, were tried, but only limited success was achieved
Scope of the Enantioselective [4 + 1] Annulation/
Rearrangement Cascade. Under the optimal conditions,
experiments to probe the scope of the nitroolefin component
have been implemented. As highlighted in Scheme 4, reactions
with a wide range of nitroolefins with varying electronic/steric
functional groups on the benzene ring all proceed well. For
instance, the electron-rich, electron-neutral, and electron-
deficient β-nitrostyrenes could give the corresponding products
in good results with 56−71% yields, >95:5 d.r., and up to 95:5
e.r. (Scheme 4, 5aa−5af). Moreover, variation of the substitute
position proved to be feasible. For example, when meta-bromo
sustituted nitrostyrene was applied, good yields and excellent
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Scheme 4. Scope of Nitroolefins for the Enantioselective Cascade [4 + 1] Annulation/Rearrangement Reaction
(Scheme 4, 5ak, 20% yield, >95:5 d.r., and 33:67 e.r.), and the
work to further improve these results is currently ongoing in
our laboratory.
graphic analysis (see the Supporting Information),24 and other
oxazolidinone products could be tentatively assigned according
to an analogous enantioinduction. It is worth noting that these
experimental results confirmed the rationality of our proposed
stereochemically controlled mechanism, as depicted in Scheme
3.
This asymmetric cascade reaction to access chiral oxazolidi-
nones is also general with respect to stable sulfur ylides, as
revealed in Scheme 5. When aromatic sulfur ylides were
utilized, variation of electronic contribution of substituents on
the benzene ring is possible without obvious loss in
stereoselectivity (Scheme 5, 5aa−5fa: 44−71% yields, >95:5
d.r., and 94:6−96:4 e.r.). A bulky meta-substituted substrate was
also efficient in this transformation, such as meta-bromo sulfur
ylide, giving the desired product 5ga in 50% yield, >95:5 d.r.,
and 91:9 e.r. It was noted that halogenated chiral oxazolidin-2-
ones should be valuable precursors for many further trans-
formations.23 Moreover, the scope of sulfur ylides could be
significantly extended to heteroaryl and alkylacyl ylides. For
example, when a 2-thiophenyl incorporated substrate was
applied, the enantioenriched oxazolidinone, including the
heteroarene architecture, could be obtained in moderated
yield and excellent stereoselectivities (Scheme 5, 5ha: 58%
yield, >95:5 d.r., and 95:5 e.r.). In addition, the (2-
phenylpropyl)acyl ylide can also react with nitroolefin 4i to
afford the desired product in moderate yield and with excellent
stereoselectivities (Scheme 5, 5ii: 46% yield, 78:22 e.r., and
>95:5 d.r.).
Enantioselective [4 + 1]/[3 + 2] Cycloaddition
Cascade. On the basis of the above success, we further
evaluated the axial-to-central chirality transfer strategy in the
asymmetric [4 + 1]/[3 + 2] cylcoaddition cascade. For
example, with mixed fluorobenzene/CHCl3 (1:4) as the
solvent,21 axially chiral sulfur ylide 3a reacted with acrylate-
tethered nitrostyrene 6a and enantioenriched fused heterocycle
7aa was delivered in high chemoselectivity and diastereose-
lectivity, though in moderate enantioselectivity (95% yield,
>95:5 d.r., 81:19 e.r.). As highlighted in Scheme 6, a range of
acrylate-tethered nitroolefins, including electron-neutral, elec-
tron-rich, and electron-deficient substituents, at the para
position of the oxygen atom could be well tolerated, leading
to desired fused heterocycles in high yields and moderate
enantioselectivities (Scheme 6, 7aa−7ad: 75−95% yields,
77:23−81:19 e.r.). Variation of the electronic properties on
sulfur ylides proved to be feasible, and moderate to good yields
with good enantioselectivities were achieved (Scheme 6, 7aa−
7ca: 54−95% yields, >95:5 d.r., and 81:19−87:13 e.r.). Note
that the axially chiral sulfide 2 as an efficient stereocontroller
could induce the generation of five sequential stereocenters.
The absolute configuration of oxazolidinone 5fa was
unambiguously confirmed to be (4S,5R) by X-ray crystallo-
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Scheme 5. Scope of Stable Sulfur Ylides for the Enantioselective Cascade [4 + 1] Annulation/Rearrangement Reaction
Scheme 6. Representative Results of Enantioselective [4 + 1]/[3 + 2] Cascade Reactions
nitrostyrene, efficiently affording enantioenriched fused hetero-
cycles in excellent yields and high stereoselectivities. Other
related asymmetric transformations based on this protocol will
be reported in due course.
CONCLUSION
■
In summary, we have described two types of enantioselective
cascade reactions of stable sulfur ylides and nitroolefins by
virtue of the efficient axial-to-central chirality transfer strategy.
The formal [4 + 1] annulation/rearrangement cascade
delivered optically active oxazolidinones in a concise way
with excellent stereoselectivities. In addition, the same strategy
has been further extended to asymmetric [4 + 1]/[3 + 2]
cycloaddition cascades of sulfur ylides and acrylate-tethered β-
EXPERIMENTAL SECTION
■
Representative Procedure for the Enantioselective [4 + 1]
Annulation/Rearrangement Cascade. To a 50 mL flask equipped
with a magnetic stir bar was added nitroolefin 4 (0.2 mmol, 1.0 equiv),
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1-(2-chlorophenyl)thiourea (2-CTU, 0.02 mmol, 3.73 mg, 0.1 equiv),
N,N-dimethylaminopyridine (DMAP, 0.02 mmol, 2.44 mg, 0.1 equiv),
and toluene/CH2Cl2 (4:1, 20 mL). This solution was stirred at
ambient temperature for 0.5 h, and then chiral sulfur ylide 3 (0.25
mmol, 1.25 equiv) was introduced and continued to stir for 24−48 h
at the same temperature. Upon the completion of the reaction
monitored by TLC, the solvent was removed under reduced pressure.
The crude product was purified by flash chromatography on silica gel
(silica, 200−300; eluant, petroleum ether/dichloromethane/ethyl
acetate (5:1:1−3:1:1)) to provide pure product 5. The absolute
configuration of oxazolidinone 5 was assigned by the X-ray
crystallographic analysis of 5fa according to an analogous enantioin-
301.3. Anal. Calcd for (C16H12ClNO3): C, 63.69; H, 4.01; N, 4.64.
Found: C, 63.75; H, 3.65; N, 4.48.
(4S,5R)-5-Benzoyl-4-(4-bromophenyl)oxazolidin-2-one (5af): 56%
yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio, 93:7.
Daicel Chirapak OD-H, hexane/isopropanol = 85/15, flow rate = 1.0
mL/min, tR = 27.29 min (major), tR = 42.08 min (minor). [α]D27 = −50
(c = 2.2, CHCl3). 1H NMR (600 MHz, CDCl3): δ (ppm) 7.97 (d, J =
7.6 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.56 (d, J = 8.3 Hz, 2H), 7.49 (t,
J = 7.7 Hz, 2H), 7.31 (d, J = 8.3 Hz, 2H), 5.79 (s, 1H), 5.39 (d, J = 5.9
Hz, 1H), 5.36 (d, J = 5.7 Hz, 1H). 13C NMR (150 MHz, CDCl3 +
DMSO-d6 (9:1)): δ (ppm) 191.8, 156.4, 138.1, 133.3, 132.6, 131.0,
128.1, 127.8, 127.2, 121.2, 81.1, 55.7. MS: m/z [M + 2]+ = 347.6. Anal.
Calcd for C16H12BrNO3: C, 55.51; H, 3.49; N, 4.05. Found: C, 55.40;
H, 3.38; N, 3.98.
1
duction. The diastereomer ratio was determined by H NMR of the
reaction mixture. The enantiomeric ratio was determined by chiral
HPLC at 25 °C using a UV detector tuned for 254 nm.
(4S,5R)-5-Benzoyl-4-(3-bromophenyl)oxazolidin-2-one (5ag):
68% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
95:5. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
(4S,5R)-5-Benzoyl-4-phenyloxazolidin-2-one (5aa): 71% yield;
white solid; diastereomeric ratio, >95:5; enantiomeric ratio, 95:5.
Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate = 0.7
mL/min, tR = 21.32 min (major), tR = 26.63 min (minor). [α]D27 = −82
(c = 2.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.94 (d, J =
8.0 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.47 (t, J = 6.4 Hz, 2H), 7.44−
7.34 (m, 5H), 6.30 (s, 1H), 5.46 (d, J = 5.2 Hz, 1H), 5.32 (d, J = 5.6
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 192.3, 157.7, 139.0,
134.4, 133.6, 129.4, 129.3, 129.0, 128.8, 126.3, 83.3, 57.0. MS: m/z =
268.4. Anal. Calcd for (C16H13NO3): C, 71.90; H, 4.90; N, 5.24.
Found: C, 72.13; H, 5.14; N, 5.58.
1.0 mL/min, tR = 18.45 min (major), tR = 24.37 min (minor). [α]D27
=
−89 (c = 2.4, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.93 (d,
J = 7.2 Hz, 2H), 7.61 (t, J = 7.0 Hz, 1H), 7.48−7.44 (m, 2H), 7.32−
7.28 (m, 1H), 6.96−6.87 (m, 3H), 6.53 (d, J = 6.0 Hz, 1H), 5.26 (d, J
= 4.8 Hz, 1H), 3.79 (s, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm)
192.3, 160.2, 157.8, 140.6, 134.4, 133.6, 130.4, 129.3, 128.8, 118.3,
114.5, 111.6, 83.1, 57.0, 55.3. MS: m/z = 345.7 (M + 2 = 347.8). Anal.
Calcd for (C16H12BrNO3): C, 55.51; H, 3.49; N, 4.05. Found: C,
55.64; H, 3.19; N, 4.01.
(4S,5R)-5-Benzoyl-4-(2-methoxyphenyl)oxazolidin-2-one (5ah):
65% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
88:12. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate
= 0.7 mL/min, tR = 18.77 min (major), tR = 24.82 min (minor). [α]D27
= −50 (c = 1.7, CHCl3). 1H NMR (600 MHz, CDCl3): δ (ppm) 7.98
(d, J = 7.5 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H),
7.42−7.29 (m, 2H), 7.04 (t, J = 7.4 Hz, 1H), 6.89 (d, J = 8.2 Hz, 1H),
5.59 (d, J = 4.5 Hz, 1H), 5.52 (d, J = 4.3 Hz, 2H), 3.64 (s, 3H). 13C
NMR (100 MHz, CDCl3 + DMSO-d6 (9:1)): δ (ppm) 192.6, 157.7,
155.4, 133.6, 133.4, 128.9, 128.3, 128.1, 127.1, 125.7, 120.1, 109.9,
79.8, 54.2, 52.5. MS: m/z = 297.6. Anal. Calcd for C17H15NO4: C,
68.68; H, 5.09; N, 4.71. Found: C, 68.57; H, 5.02; N, 4.62.
(4S,5R)-5-Benzoyl-4-(4-methoxyphenyl)oxazolidin-2-one (5ab):
63% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
95:5. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
0.7 mL/min, tR = 37.26 min (major), tR = 49.28 min (minor). [α]D27
=
1
−103 (c = 2.2, CHCl3). H NMR (400 MHz, CDCl3): δ (ppm) 7.94
(d, J = 7.6 Hz, 2H), 7.62 (t, J = 7.6 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H),
7.33 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 5.88 (s, 1H), 5.45
(d, J = 5.6 Hz, 1H), 5.24 (d, J = 5.6 Hz, 1H), 3.82 (s, 3H). 13C NMR
(100 MHz, CDCl3 + DMSO-d6 (9:1)): δ (ppm) 191.9, 158.3, 156.2,
132.8, 132.2, 130.5, 127.6, 127.4, 126.3, 112.9, 81.0, 55.7, 53.8. MS: m/
z = 297.3. Anal. Calcd for (C17H15NO4): C, 68.68; H, 5.09; N, 4.71.
Found: C, 68.83; H, 5.30; N, 4.59.
(4S,5R)-5-Benzoyl-4-(naphthalen-1-yl)oxazolidin-2-one (5ai):
71% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
92:8. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
(4S,5R)-5-Benzoyl-4-p-tolyloxazolidin-2-one (5ac): 67% yield;
white solid; diastereomer ratio, >95:5; enantiomeric ratio, 95:5. Daicel
Chirapak OD-H, hexane/isopropanol = 80/20, flow rate = 1.0 mL/
min, tR = 17.30 min (major), tR = 19.98 min (minor). [α]D27 = −64 (c =
1.0 mL/min, tR = 23.07 min (minor), tR = 38.55 min (major). [α]D27
=
74 (c = 1.3, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ (ppm) 8.01 (d,
J = 8.0 Hz, 2H), 7.95−7.88 (m, 3H), 7.71 (d, J = 7.2 Hz, 1H), 7.63−
7.44 (m, 6H), 6.34 (d, J = 3.6 Hz, 1H), 5.83 (s, 1H), 5.51 (d, J = 3.6
Hz, 1H). 13C NMR (100 MHz, CDCl3 + DMSO-d6 (9:1)): δ (ppm)
192.9, 157.4, 135.1, 133.9, 133.5, 133.5, 129.5, 129.2, 128.7, 128.3,
126.5, 125.7, 125.1, 123.1, 121.8, 113.9, 81.9, 52.7. MS: m/z = 317.2.
Anal. Calcd for (C20H15NO3): C, 75.70; H, 4.76; N, 4.41. Found: C,
75.79; H, 4.96; N, 4.41.
1
2.2, CHCl3). H NMR (600 MHz, CDCl3): δ (ppm) 7.89 (d, J = 5.8
Hz, 2H), 7.58 (s, 1H), 7.43 (s, 2H), 7.24 (d, J = 5.5 Hz, 2H), 7.18 (s,
2H), 6.78 (s, 1H), 5.40 (s, 1H), 5.18 (s, 1H), 2.33 (s, 3H). 13C NMR
(150 MHz, CDCl3): δ (ppm) 192.4, 158.0, 138.7, 136.0, 134.2, 133.6,
129.7, 129.2, 128.7, 126.1, 83.2, 57.0, 21.0. MS: m/z = 281.8. Anal.
Calcd for C17H15NO3: C, 72.58; H, 5.37; N, 4.98. Found: C, 72.49; H,
5.27; N, 4.88.
(4S,5R)-5-Benzoyl-4-(4-fluorophenyl)oxazolidin-2-one (5ad): 68%
yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio, 95:5.
Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate = 1.0
mL/min, tR = 14.72 min (major), tR = 19.11 min (minor). [α]D27 = −96
(c = 1.4, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.96 (d, J =
8.0 Hz, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.42−
7.39 (m, 2H), 7.11 (t, J = 8.8 Hz, 2H), 5.97 (s, 1H), 5.41 (d, J = 5.6
Hz, 1H), 5.36 (d, J = 5.6 Hz, 1H). 13C NMR (100 MHz, CDCl3 +
DMSO-d6 (9:1)): δ (ppm) 192.4, 163.5, 161.0, 157.2, 135.2, 134.0,
133.3, 128.8, 128.4, 127.8, 127.8, 115.7, 115.5, 82.4, 56.3. MS: m/z =
285.9. Anal. Calcd for (C16H12FNO3): C, 67.36; H, 4.24; N, 4.91.
Found: C, 67.27; H, 4.54; N, 4.82.
(4S,5R)-5-Benzoyl-4-(3,4-difluorophenyl)oxazolidin-2-one (5aj):
50% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
92:8. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
1.0 mL/min, tR = 13.49 min (major), tR = 16.20 min (minor). [α]D27
=
−25 (c = 2.2, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.97 (d,
J = 8.1 Hz, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H),
7.35−7.24 (m, 1H), 7.25−7.11 (m, 2H), 6.58 (s, 1H), 5.38 (s, 2H).
13C NMR (150 MHz, CDCl3): δ (ppm) 193.1, 157.8, 155.6, 133.8,
133.5, 129.1, 128.6, 128.3, 127.4, 125.9, 120.3, 110.1, 79.9, 54.4, 52.6.
MS: m/z = 303.0. Anal. Calcd for C16H11F2NO3: C, 63.37; H, 3.66; N,
4.62. Found: C, 63.27; H, 3.55; N, 4.53.
(4S,5R)-5-Benzoyl-4-(4-chlorophenyl)oxazolidin-2-one (5ae): 68%
yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio, 94:6.
Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate = 0.7
mL/min, tR = 22.55 min (major), tR = 30.42 min (minor). [α]D27 = −66
(c = 1.4, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.94 (d, J =
7.6 Hz, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.38−
7.32 (m, 4H), 6.62 (s, 1H), 5.39 (d, J = 5.6 Hz, 1H), 5.32 (d, J = 6.0
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 192.2, 157.7, 137.5,
134.9, 134.6, 133.6, 129.4, 129.4, 128.9, 127.7, 83.2, 56.6. MS: m/z =
(4S,5R)-5-Benzoyl-4-isopropyloxazolidin-2-one (5ak): 20% yield;
white solid; diastereomer ratio, >95:5; enantiomeric ratio, 67:33.
Daicel Chirapak AD-H, hexane/isopropanol = 85/15, flow rate = 1.0
mL/min, tR = 9.59 min (major), tR = 22.75 min (minor). [α]D27 = −35
(c = 0.53, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 8.03 (d, J =
7.6 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 6.29 (s,
1H), 5.33 (d, J = 4.4 Hz, 1H), 4.10 (t, J = 5.2 Hz, 1H), 1.94−1.86 (m,
1H), 1.03 (d, J = 6.8 Hz, 3H), 0.96 (d, J = 6.8 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ (ppm) 193.5, 158.4, 134.1, 129.3, 128.8, 79.3, 59.0,
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Article
32.4, 18.0, 17.3. MS: m/z = 234.1. Anal. Calcd for (C13H15NO3): C,
66.94; H, 6.48; N, 6.00. Found: C, 66.58; H, 6.28; N, 5.90.
rate = 1.0 mL/min, tR = 16.35 min (major), tR = 10.67 min (minor).
1
[α]D26 = −36 (c = 1.8, CH2Cl2). H NMR (600 MHz, CDCl3): δ 7.89
(4S,5R)-5-(4-Methoxybenzoyl)-4-phenyloxazolidin-2-one (5ba):
49% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
94:6. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
(d, J = 3.5 Hz, 1H), 7.78 (d, J = 4.7 Hz, 1H), 7.41 (s, 4H), 7.39−7.34
(m, 1H), 7.16 (t, J = 4.2 Hz, 1H), 6.42 (s, 1H), 5.29 (d, J = 5.4 Hz,
1H), 5.23 (d, J = 5.5 Hz, 1H). 13C NMR (150 MHz, CDCl3): δ 186.2,
157.7, 140.2, 139.0, 136.2, 135.1, 129.3, 129.0, 128.7, 126.2 84.3, 57.8.
HRMS (ESI) Calcd for C14H11NO3S [M + Na+]: 296.0357. Found:
296.0370.
1.0 mL/min, tR = 22.83 min (major), tR = 32.52 min (minor). [α]D27
=
1
−154 (c = 1.6, CHCl3). H NMR (600 MHz, CDCl3): δ (ppm) 7.95
(d, J = 8.8 Hz, 2H), 7.42 (d, J = 3.8 Hz, 4H), 7.40−7.34 (m, 1H), 6.94
(d, J = 8.8 Hz, 2H), 5.82 (s, 1H), 5.42 (d, J = 5.7 Hz, 1H), 5.36 (d, J =
5.3 Hz, 1H), 3.88 (s, 3H). 13C NMR (100 MHz, CDCl3+ DMSO-d6
(9:1)): δ (ppm) 190.9, 164.3, 158.0, 139.6, 131.6, 129.0, 128.6, 126.3,
114.0, 82.6, 57.4, 55.5. MS: m/z = 297.6. Anal. Calcd for
(C17H15NO4): C, 68.68; H, 5.09; N, 4.71. Found: C, 68.57; H, 5.37;
N, 4.71.
(4S,5R)-4-(Naphthalen-1-yl)-5-(3-phenylpropanoyl)-oxazolidin-2-
one (5ii): 46% yield; white solid; diastereomer ratio, >95:5;
enantiomeric ratio, 78:22. Daicel Chirapak OD-H, hexane/isopropanol
= 70/30, flow rate = 1.0 mL/min, tR = 30.30 min (major), tR = 13.73
1
min (minor). [α]D27 = 30 (c = 2.9, CHCl3). H NMR (600 MHz,
CDCl3): δ (ppm) 8.13 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H),
7.86 (d, J = 8.4 Hz, 1H), 7.61−7.53 (m, 3H), 7.48 (t, J = 7.5 Hz, 1H),
7.28 (t, J = 7.2 Hz, 2H), 7.22−7.19 (m, 3H), 6.03 (s, 1H), 5.80 (s,
1H), 4.65 (d, J = 2.4 Hz, 1H), 3.17−2.99 (m, 4H). 13C NMR (100
MHz, CDCl3): δ (ppm) 207.0, 158.3, 140.1, 134.2, 133.9, 129.6, 129.4,
129.1, 128.5, 128.3, 127.1, 126.3, 125.3, 122.6, 122.1, 85.4, 54.8, 40.8,
28.8. HRMS (ESI) Calcd for C22H19NO3 [M + Na+]: 368.1263.
Found: 368.1265.
Representative Procedure for the Enantioselective Cascade
[4 + 1]/[3 + 2] Cycloaddition. To the solution of nitroolefin 6a (0.1
mmol, 1.0 equiv, 26.3 mg) in CHCl3/F-benzene ((4:1), 5 mL) was
added chiral sulfur ylide 3a (0.125 mmol, 1.25 equiv, 53.82 mg). The
reaction mixture was stirred for 72 h at room temperature. Upon the
completion of the reaction monitored by TLC, the solvent was
removed under reduced pressure. The crude product was purified by
flash chromatography on silica gel (silica, 200−300; eluant, petroleum
ether/dichloromethane/acetone (10:3:1)) to provide pure product
7aa. The diastereomer ratio was determined by 1H NMR of the
reaction mixture. The enantiomeric ratio was determined by chiral
HPLC at 25 °C using a UV detector tuned for 254 nm.
(4S,5R)-5-(4-Methylbenzoyl)-4-phenyloxazolidin-2-one (5ca):
69% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
96:4. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
1.0 mL/min, tR = 14.34 min (major), tR = 22.12 min (minor). [α]D27
=
−97 (c = 1.8, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.83 (d,
J = 5.2 Hz, 1H), 7.36−7.41 (m, 5H), 7.26 (d, J = 5.2 Hz, 2H), 6.63 (s,
1H), 5.44 (d, J = 3.6 Hz, 1H), 5.28 (d, J = 3.2 Hz, 1H), 2.42 (s, 3H).
13C NMR (100 MHz, CDCl3): δ (ppm) 191.8, 158.0, 145.5, 139.1,
131.1, 129.5, 129.4, 129.3, 128.9, 126.3, 83.2, 57.2, 21.7. MS: m/z =
282.2. Anal. Calcd for (C17H15NO3): C, 72.58; H, 5.37; N, 4.98.
Found: C, 72.35; H, 5.54; N, 4.75.
(4S,5R)-5-(4-Fluorobenzoyl)-4-phenyloxazolidin-2-one (5da):
54% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
96:4. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
1.0 mL/min, tR = 17.10 min (major), tR = 20.97 min (minor). [α]D27
=
−94 (c = 1.4, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 8.80 (s,
1H), 8.48 (d, J = 8.2 Hz, 1H), 8.34 (d, J = 7.8 Hz, 1H), 7.73 (t, J = 8.0
Hz, 1H), 7.58−7.32 (m, 5H), 6.03 (s, 1H), 5.49−5.44 (m, 2H). 13C
NMR (100 MHz, CDCl3 + DMSO-d6 (9:1)): δ (ppm) 191.0, 156.7,
147.7, 138.9, 134.6, 129.8, 128.7, 128.4, 127.8, 125.8, 123.7, 82.5, 56.4.
MS: m/z = 285.5. Anal. Calcd for C16H12FNO3: C, 67.36; H, 4.24; N,
4.91. Found: C, 67.23; H, 4.15; N, 4.82.
Ethyl (1R,4S,4aS,9bR,9cR)-1-(Phenylcarbonyl)-4,4a,9b,9c-tetrahy-
dro-1H-2,3,5-trioxa-2a-azapentaleno[1,6-ab]nap-hthalene-4-car-
boxylate (7aa): 95% yield; white solid; diastereomer ratio, >95:5;
enantiomeric ratio, 81:19. Daicel Chirapak OD-H, hexane/isopropanol
= 70/30, flow rate = 1.0 mL/min, tR = 10.96 min (major), tR = 13.84
(4S,5R)-5-(4-Chlorobenzoyl)-4-phenyloxazolidin-2-one (5ea):
51% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
96:4. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate =
min (minor). [α]D27 = +12.3 (c = 2.1, CHCl3). H NMR (400 MHz,
1
CDCl3): δ (ppm) 8.00 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.2 Hz, 1H),
7.42 (t, J = 7.6 Hz, 2H), 7.33 (d, J = 7.6 Hz, 1H), 7.23 (t, J = 7.6 Hz,
1H), 7.01 (d, J = 8.0 Hz, 2H), 5.41 (d, J = 8.8 Hz, 1H), 5.11 (s, 1H),
5.10 (s, 1H), 4.52 (t, J = 7.8 Hz, 1H), 4.42 (t, J = 9.0 Hz, 1H), 4.31 (q,
J = 7.2 Hz, 2H), 1.34 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ (ppm) 192.4, 168.0, 153.2, 134.8, 134.1, 130.0, 129.5,
129.1,128.5, 123.6, 121.7, 117.8, 85.6, 82.7, 81.6, 73.9, 62.2, 41.7, 14.1.
MS: m/z = 382.3 ([M + H]+). Anal. Calcd for (C21H19NO6): C,
66.13; H, 5.02; N, 3.67. Found: C, 65.95; H, 4.74; N, 3.53.
1.0 mL/min, tR = 18.02 min (major), tR = 21.97 min (minor). [α]D27
=
1
−103 (c = 1.2, CHCl3). H NMR (400 MHz, CDCl3): δ (ppm) 7.93
(d, J = 8.4 Hz, 2H), 7.41−7.47 (m, 7H), 5.57 (s, 1H), 5.39 (s, 2H).
13C NMR (100 MHz, CDCl3): δ (ppm) 191.2, 157.4, 141.1, 138.8,
132.0, 130.8, 129.3, 129.2, 129.1, 126.3, 83.4, 56.9. MS: m/z = 302.0.
Anal. Calcd for (C16H12ClNO3): C, 63.69; H, 4.01; N, 4.64. Found: C,
63.85; H, 4.29; N, 4.57.
(4S,5R)-5-(4-Bromobenzoyl)-4-phenyloxazolidin-2-one (5fa): 44%
yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio, 96:4.
Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow rate = 1.0
mL/min, tR = 20.10 min (major), tR = 24.01 min (minor). [α]D27 = −69
(c = 3.6, CHCl3). 1H NMR (400 MHz, CDCl3): δ (ppm) 7.84 (d, J =
8.5 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H), 7.46−7.37 (m, 5H), 5.87 (s,
1H), 5.41−5.37 (m, 2H). 13C NMR (100 MHz, CDCl3 + DMSO-d6
(9:1)): δ (ppm) 191.2, 156.4, 138.7, 131.4, 131.0, 129.7, 128.3, 128.0,
127.6, 125.3, 81.3, 56.1. MS: m/z [M + 1]+ = 347.7. Anal. Calcd for
C16H12BrNO3: C, 55.51; H, 3.49; N, 4.05. Found: C, 55.38; H, 3.34;
N, 3.99.
Ethyl (1R,4S,4aS,9bR,9cR)-8-Methyl-1-(phenylcarbonyl)-
4,4a,9b,9c-tetrahydro-1H-2,3,5-trioxa-2a-azapentaleno-[1,6-ab]-
naphthalene-4-carboxylate (7ab): 75% yield; white solid; diaster-
eomer ratio, >95:5; enantiomeric ratio, 79:21. Daicel Chirapak OD-H,
hexane/isopropanol = 70/30, flow rate = 1.0 mL/min, tR = 8.62 min
(major), tR = 10.89 min (minor). [α]D26 = +35.6 (c = 1.9, CHCl3). H
1
NMR (600 MHz, CDCl3): δ (ppm) 8.01 (d, J = 7.8 Hz, 2H), 7.57 (t, J
= 7.2 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H), 7.12 (s, 1H), 7.03 (d, J = 8.4
Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 5.41 (d, J = 9.0 Hz, 1H), 5.10 (d, J
= 1.8 Hz, 1H), 5.07 (dd, J1 = 2.4 Hz, J2 = 6.6 Hz, 1H), 4.90 (dd, J1 =
6.0 Hz, J2 = 9.0 Hz, 1H), 4.38 (t, J = 9.0 Hz, 1H), 4.33−4.29 (m, 2H),
2.26 (s, 1H), 1.35 (t, J = 7.2 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ
(ppm) 192.6, 168.1, 150.9, 134.9, 134.0, 133.1, 130.3, 129.6, 129.5,
128.5, 121.5, 117.5, 85.6, 82.8, 81.6, 74.0, 62.1, 41.8, 20.6, 14.1. MS:
m/z = 396.4 ([M + H]+). Anal. Calcd for (C22H21NO6): C, 66.83; H,
5.35; N, 3.54. Found: C, 66.95; H, 5.53; N, 3.52.
(4S,5R)-5-(3-Bromobenzoyl)-4-phenyloxazolidin-2-one (5ga):
50% yield; white solid; diastereomer ratio, >95:5; enantiomeric ratio,
91:9. Daicel Chirapak AD-H, hexane/isopropanol = 70/30, flow rate =
1.0 mL/min, tR = 22.63 min (major), tR = 11.60 min (minor). [α]D27
=
−60 (c = 1.6, CH2Cl2). 1H NMR (600 MHz, CDCl3): δ 8.07 (s, 1H),
7.87 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.44−7.34 (m, 6H),
6.34 (s, 1H), 5.39 (d, J = 5.6 Hz, 1H), 5.34 (d, J = 5.6 Hz, 1H). 13C
NMR (150 MHz,CDCl3): δ 191.1, 157.5, 138.7, 137.3, 135.3, 132.3,
130.4, 129.4, 129.1, 128.0, 126.3, 123.1, 83.3, 56.9. HRMS (ESI) Calcd
for C16H12BrNO3 [M + Na+]: 367.9898. Found: 367.9897.
Ethyl (1R,4S,4aS,9bR,9cR)-1-(Phenylcarbonyl)-4,4a,9b,9c-tetrahy-
dro-1H-2,3,5-trioxa-2a-azapen-taleno[1,6-ab]na-phthalene-4-car-
boxylate (7ac): 91% yield; white solid; diastereomer ratio, >95:5;
enantiomeric ratio, 81:19. Daicel Chirapak OD-H, hexane/isopropanol
= 70/30, flow rate = 1.0 mL/min, tR = 10.55 min (major), tR = 13.77
(4S,5R)-4-Phenyl-5-(thiophene-2-carbonyl)oxazolidin-2-one
(5ha): 58% yield; white solid; diastereomer ratio, >95:5; enantiomeric
ratio, 95:5. Daicel Chirapak OD-H, hexane/isopropanol = 80/20, flow
min (minor). [α]D26 = +36.1 (c = 2.5, CHCl3). H NMR (600 MHz,
1
CDCl3): δ (ppm) 8.04 (d, J = 7.8 Hz, 2H), 7.60−7.58 (m, 1H), 7.45
1078
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The Journal of Organic Chemistry
Article
(t, J = 7.8 Hz, 2H), 7.37 (s, 1H), 7.20 (dd, J1 = 1.8 Hz, J2 = 8.4
Hz,1H), 6.97 (d, J = 8.4 Hz, 1H), 5.38 (d, J = 9.0 Hz, 1H), 5.11 (d, J =
6.6 Hz, 1H), 5.09 (s, 1H), 4.50 (dd, J1 = 6.6 Hz, J2 = 9.6 Hz, 1H), 4.40
(t, J = 9.0 Hz, 1H), 4.33−4.30 (m, 2H), 1.35 (t, J = 7.2 Hz, 3H). 13C
NMR (150 MHz, CDCl3): δ (ppm) 192.1, 167.8, 151.7, 134.6, 134.2,
129.7, 129.5, 129.1, 128.6, 128.4, 123.4, 119.2, 85.7, 82.8, 81.4, 73.4,
62.2, 41.3, 14.0. MS: m/z = 416.2 ([M + H]+). Anal. Calcd for
(C21H18ClNO6): C, 60.66; H, 4.36; N, 3.37. Found: C, 60.79; H, 4.47;
N, 3.18.
Ethyl (1R,4S,4aS,9bR,9cR)-1-(Phenylcarbonyl)-4,4a,11c,11d-tetra-
hydro-1H-2,3,5-trioxa-2a-azapentaleno[1,6-bc]p-henanthrene-4-
carboxylate (7ad): 87% yield; white solid; diastereomer ratio, >95:5;
enantiomeric ratio, 77:23. Daicel Chirapak OD-H, hexane/isopropanol
= 70/30, flow rate = 1.0 mL/min, tR = 15.62 min (minor), tR = 20.69
min (major). [α]D27 = +43.5(c = 2.1, CHCl3). Daicel Chirapak OD-H,
hexane/isopropanol = 70/30, flow rate = 1.0 mL/min, T = 25 °C, 254
nm, tR = 10.96 min (major), tR = 13.84 min (minor). [α]D27 = +12.3 (c
= 2.1, CHCl3). 1H NMR (600 MHz, CDCl3): δ (ppm) 8.20 (d, J = 8.4
Hz, 1H), 7.91 (dd, J1 = 1.2 Hz, J2 = 8.4 Hz, 2H), 7.77 (dd, J1 = 8.4 Hz,
J2 = 13.2 Hz, 2H), 7.55−7.52 (m, 1H), 7.50−7.47 (m, 1H), 7.40 (t, J =
7.5 Hz, 1H), 7.34 (t, J = 7.8 Hz, 2H), 7.25 (d, J = 9.0 Hz, 1H), 5.39−
5.33 (m, 3H), 5.02 (dd, J1 = 1.8 Hz, J2 = 6.0 Hz, 1H), 4.58 (dd, J1 = 6.6
Hz, J2 = 8.4 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.36 (t, J = 7.2 Hz, 3H).
13C NMR (150 MHz, CDCl3): δ (ppm) 194.1, 167.8, 152.2, 134.7,
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: wxiao@mail.ccnu.edu.cn.
ACKNOWLEDGMENTS
■
We are grateful to the National Science Foundation of China
(Nos. 20872043, 21072069, and 21002036), the National Basic
Research Program of China (2011CB808603), and Central
China Normal University for support of this research.
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133.7, 131.5, 130.5, 129.6, 129.4, 128.5, 128.4, 127.2, 124.6, 122.3,
118.6, 116.0, 84.7, 84.5, 82.8, 75.7, 62.2, 37.6, 14.1. MS: m/z =
432.5([M + H]+). Anal. Calcd for (C25H21NO6): C, 69.60; H, 4.91; N,
3.25. Found: C, 69.48; H, 5.18; N, 3.03.
Ethyl (1R,4S,4aS,9bR,9cR)-1-[(4-Methylphenyl)-carbon-yl]-
4,4a,9b,9c-tetrahydro-1H-2,3,5-trioxa-2a-azapentaleno [1,6-ab]-
naphthalene-4-carboxylate (7ba): 54% yield; white solid; diaster-
eomer ratio, >95:5; enantiomeric ratio, 87:13. Daicel Chirapak OD-H,
hexane/isopropanol = 70/30, flow rate = 1.0 mL/min, tR = 11.32 min
(major), tR = 16.39 min (minor). [α]D27 = +15.7 (c = 1.4, CHCl3).1H
NMR (600 MHz, CDCl3): δ (ppm) 7.91 (d, J = 7.2, 2H), 7.34 (d, J =
7.8 Hz, 1H), 7.25−7.22 (m, 3H), 7.02 (t, J = 8.1 Hz, 2H), 5.40 (d, J =
9.0 Hz, 1H), 5.11 (t, J = 6.6 Hz, 2H), 4.53−4.51 (m, 1H), 4.42 (t, J =
9.0 Hz, 1H), 4.33−4.30 (m, 2H), 2.39 (s, 1H), 1.35 (t, J = 7.2 Hz,
3H). 13C NMR (150 MHz, CDCl3): δ (ppm) 191.9, 168.1, 153.2,
145.2, 132.5, 130.0, 129.6, 129.3, 129.1, 123.6, 121.7, 117.8, 85.7, 82.7,
81.5, 73.9, 62.2, 41.7, 21.7, 14.1. MS: m/z = 395.5 (M+). Anal. Calcd
for (C22H21NO6): C, 66.83; H, 5.35; N, 3.54. Found: C, 67.04; H,
5.11; N, 3.40.
Ethyl (1R,4S,4aS,9bR,9cR)-1-[(4-Fluorophenyl)carbon-yl]-
4,4a,9b,9c-tetrahydro-1H-2,3,5-trioxa-2a-azapentaleno-[1,6-ab]-
naphthalene-4-carboxylate (7ca): 78% yield; white solid; diaster-
eomer ratio, >95:5; enantiomeric ratio, 87:13. Daicel Chirapak AD-H,
hexane/isopropanol = 60/40, flow rate = 1.0 mL/min, tR = 35.82 min
(major), tR = 40.69 min (minor). [α]D27 = +14.7 (c = 2.02, CHCl3). 1H
NMR (600 MHz, CDCl3): δ (ppm) 8.06 (dd, J1 = 5.4 Hz, J2 = 8.4 Hz,
2H), 7.36 (d, J = 6.6 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 7.10 (t, J = 8.7
Hz, 2H), 7.04 (t, J = 6.9 Hz, 2H), 5.35 (d, J = 9.0 Hz, 1H), 5.12 (s,
1H), 5.11 (d, J = 6.0 Hz, 1H), 4.52 (dd, J1 = 6.0 Hz, J2 = 9.0 Hz, 1H),
4.42 (t, J = 9.3 Hz, 1H), 4.34−4.29 (m, 2H), 1.36 (t, J = 7.2 Hz, 3H).
13C NMR (150 MHz, CDCl3): δ (ppm) 191.0, 168.0, 153.3, 132.41,
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Christmann, M. Org. Lett. 2009, 11, 4116. (c) Chen, Z.; Zhang, J.
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(8) Theoretical study on the activity of stable sulfur ylides:
(a) Lakhdar, S.; Appel, R.; Mayr, H. Angew. Chem., Int. Ed. 2009,
48, 5034. (b) Appel, R.; Hartmann, N.; Mayr, H. J. Am. Chem. Soc.
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iminum- or Brønsted acid-promoted asymmetric cyclopropanation:
(c) Kunz, R. K.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127,
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132.35, 131.3, 130.0, 129.2, 123.7, 121.7, 117.9, 115.9, 115.7, 85.6,
82.8, 81.7, 74.1, 62.2, 41.8, 14.1. MS: m/z = 399.3 (M+). Anal. Calcd
for (C21H18FNO6): C, 63.16; H, 4.54; N, 3.51. Found: C, 63.10; H,
4.34; N, 3.48.
ASSOCIATED CONTENT
́
́
(e) Hartikka, A.; Slosarczyk, A. T.; Arvidsson, P. I. Tetrahedron:
■
Asymmetry 2007, 18, 1403. (f) Cheng, Y.; An, J.; Lu, L.-Q.; Luo, L.;
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Xiao, W.-J. J. Am. Chem. Soc. 2008, 130, 6946. (b) Lu, L.-Q.; Li, F.; An,
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S
* Supporting Information
Experimental details, NMR spectra, HPLC spectra of all
products, and X-ray crystallographic data (CIF) for 5fa. This
material is available free of charge via the Internet at http://
pubs.acs.org.
1079
dx.doi.org/10.1021/jo202324f | J. Org. Chem. 2012, 77, 1072−1080

The Journal of Organic Chemistry
Article
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