Base-catalyzed cyclization of N -sulfonyl propargylamides to sulfonylmethyl-substituted oxazoles via sulfonyl migration

Article abstract of DOI:10.1021/jo4004635

The reaction of N-sulfonyl propargylamides in the presence of a base catalyst selectively affords 5-sulfonylmethyl oxazoles via 1,4-sulfonyl migration. Allenes have been established as the key intermediates. Experimental evidence has been provided to support a two-step mechanism in the cyclization.

Full text of DOI:10.1021/jo4004635

Article
pubs.acs.org/joc
Base-Catalyzed Cyclization of N‑Sulfonyl Propargylamides to
Sulfonylmethyl-Substituted Oxazoles via Sulfonyl Migration
Xinzhang Yu, Xiaoyi Xin, Boshun Wan,* and Xingwei Li*
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
S
* Supporting Information
ABSTRACT: The reaction of N-sulfonyl propargylamides in the
presence of a base catalyst selectively affords 5-sulfonylmethyl oxazoles
via 1,4-sulfonyl migration. Allenes have been established as the key
intermediates. Experimental evidence has been provided to support a
two-step mechanism in the cyclization.
replacement of the alkenyl group with an acyl one may provide
an avenue for base-catalyzed cycloisomerization to access a
range of sulfonylmethyl-substituted oxazoles (Scheme 1, eq 2).
Inspired by this idea, we prepared a series of N-sulfonyl
propargylic amides from corresponding N-sulfonyl imines,
alkynes, and acyl chlorides in a one-pot procedure (Scheme 2,
eq 1).
INTRODUCTION
■
Oxazole is a common structural motif in numerous biologically
active compounds, synthetic intermediates, and pharmaceut-
icals.1 In particular, 5-sulfonylmethyloxazoles are known to
inhibit a biological pathway that is unique to arthropods, thus
showing potential controlling effects on arthroped pests.2
However, only a few methods for the synthesis of sulfonyl-
functionalized oxazoles have been reported.3 The development
of efficient and facile synthesis methods for sulfonylmethyl
oxazoles remains a challenge in synthetic organic chemistry.
Cyclization of propargylamides to oxazoles has been achieved
using transition metal,4 acid,5 and base6 catalysts. However, to
the best of our knowledge, the base-catalyzed cyclization
accompanied by sulfonyl migration7 has not been investigated
previously. Herein, we report an operationally simple base-
catalyzed cycloisomerization of N-sulfonyl propargylamides,
leading to the formation of trisubstituted oxazoles via a 1,4-
sulfonyl shift.
Scheme 2. Preparation of N-Sulfonyl Propargyl Amides
RESULTS AND DISCUSSION
■
We previously reported the base-catalyzed cyclization of 3-aza-
1,5-enynes into pyrroles via sulfonyl migration (Scheme 1, eq
1).8 On the basis of this precedent, we reasoned that
We initiated our studies of the cyclization of 1a with Cs2CO3
in DMF at room temperature, and 1a did afford the desired
product 1b9 in high yield together with concomitant
allenylamide 1c (Table 1, entry 1). A similar result was given
in CH3CN (entry 2), and considering the isolation processes
after the reaction, we chose CH3CN as the solvent to test the
efficiencies of other base catalysts. Among all the bases tested
(PPh3, Et3N, DBU, DMAP, DABCO, LiOH, t-BuOLi, K2CO3,
Na2CO3, Li2CO3, NaOAc, KOAc, CsOAc, K3PO4), only DBU
could selectively afford the oxazole (1b) after 7 h. All other
bases gave a mixture of the allene 1c and the oxazle 1b or did
not catalyze this rearrangement at all. However, there seemed
to be no straightforward correlation between the pKa and
reactivities of the different bases; for example, neither Li2CO3
nor t-BuOLi could catalyze this cyclization efficiently (entries 6,
7). DBU in another solvent, such as toluene, DCM, THF, or
Scheme 1. Design of Base-Catalyzed Sulfonyl-Migration
Cyclizations
Received: March 5, 2013
Published: April 26, 2013
© 2013 American Chemical Society
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quantitative yield when DCM was selected as the solvent
(entries 5, 14). A base catalyst proved to be necessary because
essentially no conversion was reached when it was omitted
(entry 13).
Table 1. Optimization of the Reaction Conditions for the
Construction of Oxazole
a
Next, we explored the scope and limitation of the cyclization
protocol (Table 2). Different substituted N-tosyl propargyla-
mides were subjected to the standard conditions, and a variety
of aryl-substituted N-tosyl propargylamides (R1, R2, R3 = Ar)
underwent smooth cycloisomerization, affording oxazoles in
good to excellent yields. In addition, the reaction could be
performed in 1 g scale. For example, when 1 g of 1a was
subjected to the standard conditions, 946 mg of 1b was
obtained in 95% yield. The reaction tolerated various
substituents in the aromatic ring, regardless of the electronic
effects and the position of the substituents (1a−15a). The alkyl
substitutents in the acyl unit (R3 = alkyl) were also well-
tolerated, albeit in slightly lower yields (18a−24a, 27−28a).
The acyl component could be protecting groups (such as Cbz).
For instance, 29a transformed into the corresponding oxazole
with OBn untouched. The heteroarene-substituted propargyla-
mides (26a) also could cyclize to the corresponding oxzaole,
which provided a method for preparing heteroarene-substituted
oxazoles. In contrast, the reaction was sluggish when R1 was an
alkyl group (19a), and the corresponding oxazole 19b was
obtained in 51% yield after 24 h. It is noteworthy that if the R2
in the propargylamides is an alkyl group or proton, this
cyclization could not proceed (16a, 17a, 25a) even though the
reaction time was prolonged to 24 h and the reaction
temperature was increased to 100 °C, indicating that an aryl
R2 substitution is crucial to this catalytic transformation.
Likewise, other sulfonyl groups might shift under the same
condition (Scheme 3). The yields of the oxazole products were
b
yield (%)
c
entry
base (10 mol %)
solvent
1a
1b
89
1c
1
Cs2CO3
Cs2CO3
PPh3
DMF
2
9
10
66
74
76
24
10
0
2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCM
3
20
19
10
62
82
0
85
15
14
12
3
4
Et3N
5
DABCO
t-BuOLi
Li2CO3
DBU
6
0.7
7
0
99
13
40
50
8
9
DBU
0
74
51
37
12
1
10
11
12
13
DBU
toluene
THF
0
DBU
0
DBU
EtOH
77
98
0
0.5
d
−
CH3CN
DCM
0
0
e
14
DABCO
99
a
Reaction conditions: 1a (0.05 mmol), base (10 mol %), solvent (2
mL), rt for 7 h under air. HPLC yields. Recovery of the starting
b
c
d
e
material. No base was added. For 30 min.
EtOH, provided 1b in lower yields (entries 9−12).
Interestingly, switching the base to DABCO afforded 1c as
the major product in CH3CN, which was optimized to nearly
a
Table 2. Scope of 5-(Tosylmethyl)oxazole Formation
a
b
Reaction conditions: a (0.1 mmol), DBU (10 mol %), CH3CN (2 mL), under air, rt, 7 h; the yields of b. For 24 h.
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consistently high (82−99%), regardless of the different
electronic properties of the sulfonyl group.
material 1a, the oxazole 1b, the allene 1c, and an unknown
compound 1d. In the process, 1a disappeared after 2 h, at
which time 1c reached its maximum (52%). During the next 2
h, allene 1c decayed completely, while the amount of 1b kept
increasing to a nearly quantitative yield. This suggests that 1c
might be an intermediate leading to 1b. Indeed, an X-ray
authenticated allene 38c9 was cleanly converted into oxazole
38b (98% yield) in the presence of DBU (10 mol %) in
CH3CN (Scheme 5). Noticeably, a third species 1d remained at
Scheme 3. Scope of 5-(Arylsulfonyl)methyl Oxazole
a
Formation
Scheme 5. Conversion of Allene to Oxazole
a
Reaction conditions: propargylamide a (0.1 mmol), DBU (10 mol
%), CH3CN (2 mL), rt, 7 h, under air.
Given the information in the screening of the reaction
conditions, we selected DABCO (10 mol %) in DCM as the
standard conditions for propargyl−allenyl isomerization. All N-
sulfonyl propargylamides with an aryl R2 gave the correspond-
ing allenylamides in high yields (Scheme 4). In line with the
a constant concentration during the first 3.5 h. In addition, we
also found 1d at the early stage of preparing allene 1c under the
DABCO/DCM condition. Unfortunately, we failed to isolate
this species or capture it by dienophiles. On the basis of related
reports,10 we proposed that 1d was a zwitterionic intermedi-
ate.11
a
Scheme 4. Formation of Allene Products
A mechanistic rationale is proposed for this transformation
(Scheme 6a). First, base-catalyzed 1,3-proton migration results
Scheme 6. Possible Mechanism of Sulfonyl Migration and
Cyclization
a
Reaction conditions: propargylamide a (0.1 mmol), DABCO (10 mol
b
%), DCM (2 mL), rt, 30 min, under air. For 24 h.
results of oxazole formation, if the N-sulfonyl propargylamides
were alkyl-substituted or unsubstituted at the R2 position, no
isomerization took place even after 24 h (16c, 17c, 25c).
To cast light on the reaction mechanism, we monitored the
whole conversion process of 1a using HPLC (Figure 1). There
were four species detectable in the reaction system: the starting
in the formation of allenylamides 1c, followed by nucleophilic
attack of the oxygen at the allenyl carbon to give a zwitterionic
intermediate 1d, and then rearranged to oxazole 1b via 1,4-
sulfonyl shift. Two possible pathways can be envisioned for this
1,4-sulfonyl migration:7,8 intramolecular 1,4-sulfonyl shift and
intermolecular dissociation−addition sequence. To clarify
which pathway is followed, a crossover experiment was
performed: an equimolar mixture of 1a and 31a was subjected
to the standard conditions, affording four oxazole products in a
nearly 1:1:1:1 ratio, indicating an intermolecular pathway
(Scheme 7). However, the role of DBU in the overall process is
still not fully understood; it likely facilitates the sulfonyl
dissociation (Scheme 6b).
Figure 1. Time profile of the isomerization of 1a.
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127.9, 125.6, 122.5, 87.6, 84.9, 54.6, 21.7, 21.3; HRMS (ESI-TOF) m/
z calcd for C30H25NO3SNa (M + Na)+ 502.1453, found 502.1469.
N-(1,3-Diphenylprop-2-ynyl)-4-methyl-N-tosylbenzamide (4a).
White solid, 1.4 g, 58% yield, mp 114−116 °C; 1H NMR (500
MHz, CDCl3) δ 7.78−7.71 (m, 2H), 7.57−7.51 (m, 2H), 7.45−7.39
(m, 4H), 7.36 (ddd, J = 6.1, 2.6, 0.9 Hz, 3H), 7.31−7.26 (m, 3H), 7.21
(d, J = 8.0 Hz, 2H), 7.09 (d, J = 7.9 Hz, 2H), 6.47 (s, 1H), 2.35 (d, J =
5.8 Hz, 6H); 13C NMR (126 MHz, CDCl3) δ 171.3, 144.8, 142.7,
136.4, 136.2, 132.6, 132.0, 129.4, 129.1, 128.9, 128.8, 128.8, 128.5,
128.4, 128.3, 128.2, 122.6, 87.5, 85.0, 54.7, 21.7; HRMS (ESI-TOF)
m/z calcd for C30H25NO3SNa (M + Na)+ 502.1453, found 502.1447.
3-Chloro-N-(1,3-diphenylprop-2-ynyl)-N-tosylbenzamide (5a).
Scheme 7. Crossover Experiment
1
White solid, 1.4 g, 56% yield, mp 48−49 °C; H NMR (500 MHz,
CDCl3) δ 7.81−7.73 (m, 2H), 7.53−7.48 (m, 2H), 7.45 (dd, J = 7.5,
2.0 Hz, 2H), 7.39−7.19 (m, 11H), 7.16 (d, J = 8.1 Hz, 1H), 6.59 (s,
1H), 2.39 (s, 3H), 2.16 (s, 1H); 13C NMR (126 MHz, CDCl3) δ
169.9, 145.2, 137.0, 136.0, 134.0, 132.0, 131.5, 129.7, 129.2, 129.0,
129.0, 128.6, 128.5, 128.5, 128.4, 127.9, 126.6, 122.3, 87.9, 84.5, 54.2,
21.8; HRMS (ESI-TOF) m/z calcd for C29H22ClNO3SNa (M + Na)+
522.0907, found 522.0930.
4-Chloro-N-(1,3-diphenylprop-2-ynyl)-N-tosylbenzamide (6a).
White solid, 1.1 g, 44% yield, mp 112−113 °C; 1H NMR (500
MHz, CDCl3) δ 7.82−7.75 (m, 2H), 7.56−7.48 (m, 2H), 7.43−7.38
(m, 2H), 7.38−7.31 (m, 5H), 7.31−7.26 (m, 3H), 7.26−7.23 (m, 2H),
7.23−7.18 (m, 2H), 6.52 (s, 1H), 2.37 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 170.3, 145.1, 138.2, 136.0, 136.0, 133.9, 131.9, 130.1, 129.6,
128.9, 128.6, 128.5, 128.4, 128.2, 128.0, 122.3, 87.8, 84.5, 54.3, 21.7;
HRMS (ESI-TOF) m/z calcd for C29H22ClNO3SNa (M + Na)+
522.0907, found 522.0914.
N-(1,3-Diphenylprop-2-ynyl)-3-fluoro-N-tosylbenzamide (7a).
White solid, 1.3 g, 54% yield, mp 102−103 °C; 1H NMR (500
MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), 7.52 (dd, J = 7.0, 1.3 Hz,
2H), 7.47−7.41 (m, 2H), 7.40−7.33 (m, 3H), 7.33−7.14 (m, 7H),
7.08 (dddd, J = 11.2, 8.9, 3.2, 1.7 Hz, 2H), 6.56 (s, 1H), 2.38 (s, 3H),
2.16 (s, 1H); 13C NMR (126 MHz, CDCl3) δ 169.8, 161.9 (d, J =
248.1 Hz), 145.1, 137.2 (d, J = 7.2 Hz), 135.9 (d, J = 3.0 Hz), 131.9,
129.6 (d, J = 8.2 Hz), 129.5, 128.9, 128.9, 128.5, 128.4, 128.3, 127.8,
124.2 (d, J = 3.0 Hz), 122.2, 118.6 (d, J = 21.2 Hz), 115.5 (d, J = 23.6
Hz), 87.7, 84.5, 54.2, 21.6; 19F NMR (471 MHz, CDCl3) δ −112.2;
HRMS (ESI-TOF) m/z calcd for C29H22FNO3SNa (M + Na)+
506.1202, found 506.1178.
N-(1,3-Diphenylprop-2-ynyl)-4-fluoro-N-tosylbenzamide (8a).
White solid, 1.1 g, 46% yield, mp 121−122 °C; 1H NMR (500
MHz, CDCl3) δ 7.82−7.75 (m, 2H), 7.55−7.48 (m, 2H), 7.46−7.37
(m, 4H), 7.37−7.31 (m, 3H), 7.31−7.25 (m, 3H), 7.25−7.22 (m, 2H),
6.91 (t, J = 8.7 Hz, 2H), 6.51 (s, 1H), 2.36 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 170.4, 164.9 (d, J = 253.3 Hz), 145.1, 136.1, 136.1,
131.7 (d, J = 3.1 Hz), 131.4 (d, J = 9.1 Hz), 129.6, 129.0, 128.6, 128.5,
128.4, 128.1, 122.4, 115.1 (d, J = 22.1 Hz), 87.7, 84.6, 54.4, 21.7; 19F
NMR (471 MHz, CDCl3) δ −106.5; HRMS (ESI-TOF) m/z calcd for
C29H22FNO3SNa (M + Na)+ 506.1202, found 506.1213.
CONCLUSION
■
In summary, we have developed a DBU-catalyzd cyclo-
isomerization of N-sulfonyl propargylamides to various 5-
(sulfonylmethyl)oxazoles. The allene intermediate has been
established, and both the oxazoles and the allenes have been
obtained with high selectivity. The reaction conditions are mild,
and this method may find applications in the synthesis of
complex structures.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out under air
unless otherwise indicated. All solvents were dried just before use
according to the standard procedure. Commercially available reagents
were used without further purification. HRMS spectra were produced
on a Q-TOF microspectrometer. The melting points were determined
with a binocular microscope melting apparatus and were uncorrected.
General Procedure for the Synthesis of N-Sulfonyl Prop-
argylamides (1a as an Example). To a solution of 1.3 g (5 mmol)
of N-tosylaldimines12 and 562 mg (5.5 mmol) of phenylacetylene in
dry CH2Cl2 (20 mL), was added slowly LHMDS in THF (5 mL, 1 M,
5 mmol) at −78 °C under Ar. The resulting mixture was allowed to
stand from −78 to −40 °C for about 1 h until the consumption of N-
tosylaldimines was detected by TLC. Benzoyl chloride was then added
in one portion below −40 °C and kept for 5 min. The mixture was
then stirred at rt and kept for 30 min, and then the reaction was
quenched with water. The separated organic layer was washed with
brine and dried over MgSO4. After removal of the solvent, the residue
was purified by flash column chromatography to give 1.2 g of 1a as a
white solid in 52% yield (1a−16a and 18a−37a were all prepared by
this procedure).
N-(1,3-Diphenylprop-2-ynyl)-N-tosylbenzamide (1a). White solid,
1.2 g, 52% yield, mp 139−140 °C; H NMR (400 MHz, CDCl3) δ
1
7.75 (d, J = 7.8 Hz, 2H), 7.53 (d, J = 6.7 Hz, 2H), 7.38 (dd, J = 29.1,
10.9 Hz, 8H), 7.28−7.13 (m, 7H), 6.53 (s, 1H), 2.30 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 171.1, 144.8, 136.1, 136.0, 135.1, 131.8,
131.7, 129.3, 128.8, 128.4, 128.2, 127.9, 122.3, 87.4, 84.7, 54.4, 21.5;
HRMS (ESI-TOF) m/z calcd for C29H23NO3SNa (M + Na)+
488.1296, found 488.1295.
N-(1,3-Diphenylprop-2-ynyl)-N-tosyl-3-(trifluoromethyl)-
1
benzamide (9a). White solid, 1.2 g, 45% yield, mp 80−81 °C; H
N-(1,3-Diphenylprop-2-ynyl)-2-methyl-N-tosylbenzamide (2a).
White solid, 1.0 g, 42% yield, mp 134−135 °C; 1H NMR (500
MHz, CDCl3) δ 7.68 (d, J = 8.4 Hz, 2H), 7.64−7.57 (m, 2H), 7.53−
7.47 (m, 2H), 7.40−7.28 (m, 6H), 7.25−7.17 (m, 3H), 7.12−7.06 (m,
1H), 7.03 (t, J = 8.2 Hz, 2H), 6.72 (s, 1H), 2.40 (s, 3H), 2.01 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 170.4, 144.8, 136.5, 136.4, 134.5,
131.8, 130.3, 130.1, 129.2, 128.8, 128.8, 128.4, 128.4, 128.1, 127.7,
127.3, 125.9, 124.8, 122.4, 87.1, 84.9, 53.8, 21.6, 19.0; HRMS (ESI-
TOF) m/z calcd for C30H25NO3SNa (M + Na)+ 502.1453, found
502.1430.
NMR (500 MHz, CDCl3) δ 7.80−7.75 (m, 2H), 7.61 (d, J = 7.8 Hz,
1H), 7.55 (d, J = 7.8 Hz, 1H), 7.53−7.48 (m, 2H), 7.45−7.40 (m,
3H), 7.38−7.33 (m, 4H), 7.31−7.22 (m, 5H), 6.64 (s, 1H), 2.38 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 169.9, 145.4, 136.2, 136.0 (d, J =
3.8 Hz), 132.0, 131.8, 130.5 (q, J = 33.0 Hz), 129.7, 129.1, 128.8,
128.7, 128.5, 128.4, 128.0 (d, J = 3.5 Hz), 127.9, 125.18 (dd, J = 7.4,
3.6 Hz), 123.5 (q, J = 272.7 Hz), 122.2, 88.0, 84.4, 54.1, 21.7; 19F
NMR (471 MHz, CDCl3) δ −62.9; HRMS (ESI-TOF) m/z calcd for
C30H22F3NO3SNa (M + Na)+ 556.1170, found 556.1185.
N-(1,3-Diphenylprop-2-ynyl)-N-tosyl-4-(trifluoromethyl)-
benzamide (10a). White solid, 1.3 g, 49% yield, mp 106−107 °C; 1H
NMR (500 MHz, CDCl3) δ 7.84−7.74 (m, 2H), 7.53−7.48 (m, 2H),
7.46 (d, J = 8.2 Hz, 2H), 7.43−7.32 (m, 7H), 7.32−7.24 (m, 5H), 6.59
(s, 1H), 2.38 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 170.0, 145.4,
138.8, 136.0, 135.9, 133.0 (q, J = 32.8 Hz), 131.9, 129.7, 129.1, 128.9,
128.7, 128.6, 128.6, 128.5, 127.9, 124.8 (q, J = 3.7 Hz), 123.7 (q, J =
272.5 Hz), 87.9, 84.4, 54.1, 21.8; 19F NMR (471 MHz, CDCl3) δ
N-(1,3-Diphenylprop-2-ynyl)-3-methyl-N-tosylbenzamide (3a).
1
White solid, 1.2 g, 51% yield, mp 54−56 °C; H NMR (500 MHz,
CDCl3) δ 7.79−7.72 (m, 2H), 7.55−7.50 (m, 2H), 7.47−7.42 (m,
2H), 7.39−7.32 (m, 3H), 7.31−7.26 (m, 3H), 7.22 (ddd, J = 15.3, 5.8,
0.8 Hz, 4H), 7.17−7.12 (m, 2H), 6.54 (s, 1H), 2.37 (s, 3H), 2.21 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 171.5, 144.8, 137.8, 136.4,
136.3, 135.1, 132.5, 132.0, 129.4, 129.0, 128.9, 128.5, 128.3, 128.0,
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−63.1; HRMS (ESI-TOF) m/z calcd for C30H22F3NO3SNa (M +
Na)+ 556.1170, found 556.1156.
to reach room temperature gradually. After 6 h, the reaction mixture
was quenched with saturated sodium chloride solution, extracted with
ethyl acetate, and dried over anhydrous sodium sulfate. After filtration
and evaporation, the residue was purified by flash column
chromatography to give 17a. White solid, 80 mg, 82% yield, mp
N-(3-(4-Fluorophenyl)-1-phenylprop-2-ynyl)-N-tosylbenzamide
(11a). White solid, 1.6 g, 66% yield, mp 138−139 °C; 1H NMR (500
MHz, CDCl3) δ 7.72 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 6.6 Hz, 2H),
7.46−7.37 (m, 5H), 7.32−7.24 (m, 5H), 7.21 (d, J = 8.0 Hz, 2H), 7.04
(t, J = 8.5 Hz, 2H), 6.51 (s, 1H), 2.37 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 171.2, 162.9 (d, J = 250.1 Hz), 144.9, 136.3, 136.1, 135.3,
133.9 (d, J = 8.4 Hz), 131.8, 129.5, 129.0, 128.6, 128.6, 128.4, 128.0,
128.0, 118.6 (d, J = 3.2 Hz), 115.8 (d, J = 22.1 Hz), 86.5, 84.7, 54.4,
21.7; 19F NMR (377 MHz, CDCl3) δ −110.6; HRMS (ESI-TOF) m/z
calcd for C29H22FNO3SNa (M + Na)+ 506.1202, found 506.1193.
N-(1-Phenyl-3-p-tolylprop-2-ynyl)-N-tosylbenzamide (12a).
White solid, 0.8 g, 33% yield, mp 120−122 °C; 1H NMR (500
MHz, CDCl3) δ 7.82−7.73 (m, 2H), 7.52 (d, J = 7.3 Hz, 2H), 7.40 (t,
J = 7.9 Hz, 3H), 7.34 (d, J = 6.9 Hz, 2H), 7.31−7.20 (m, 7H), 7.16 (d,
J = 7.8 Hz, 2H), 6.53 (s, 1H), 2.38 (d, J = 4.2 Hz, 6H); 13C NMR (126
MHz, CDCl3) δ 171.3, 144.8, 139.1, 136.4, 135.4, 131.9, 131.7, 129.5,
129.2, 129.0, 128.5, 128.5, 128.2, 128.0, 128.0, 119.4, 87.8, 84.2, 54.6,
21.7, 21.7; HRMS (ESI-TOF) m/z calcd for C30H25NO3SNa (M +
Na)+ 502.1453, found 502.1451.
N-(1-(2-Chlorophenyl)-3-phenylprop-2-ynyl)-N-tosylbenzamide
(13a). White solid, 1.1 g, 44% yield, mp 145−146 °C; 1H NMR (400
MHz, CDCl3) δ 8.22 (d, J = 7.7 Hz, 1H), 7.75 (d, J = 7.8 Hz, 2H),
7.61−7.54 (m, 2H), 7.47 (d, J = 7.5 Hz, 1H), 7.37 (qd, J = 15.3, 7.8
Hz, 8H), 7.25 (t, J = 7.6 Hz, 1H), 7.19 (d, J = 7.8 Hz, 1H), 7.04 (d, J =
8.1 Hz, 2H), 6.40 (s, 1H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 171.5, 144.4, 136.4, 134.9, 134.1, 133.8, 132.4, 132.2, 132.0, 130.3,
129.4, 129.0, 128.8, 128.6, 128.5, 128.2, 126.7, 122.3, 87.6, 85.3, 54.0,
21.6; HRMS (ESI-TOF) m/z calcd for C29H22ClNO3SNa (M + Na)+
522.0907, found 522.0912.
N-(1-(2-Fluorophenyl)-3-phenylprop-2-ynyl)-N-tosylbenzamide
(14a). White solid, 1.8 g, 74% yield, mp 120−122 °C; 1H NMR (500
MHz, CDCl3) δ 8.01 (td, J = 7.8, 1.2 Hz, 1H), 7.74−7.65 (m, 2H),
7.62−7.55 (m, 2H), 7.54−7.46 (m, 3H), 7.40 (ddd, J = 3.8, 3.2, 1.8
Hz, 5H), 7.32 (tdd, J = 7.3, 5.3, 1.7 Hz, 1H), 7.20 (td, J = 7.6, 1.1 Hz,
1H), 7.11 (d, J = 8.0 Hz, 2H), 6.90 (ddd, J = 10.4, 8.2, 1.0 Hz, 1H),
6.52 (s, 1H), 2.35 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 171.2,
160.9 (d, J = 249.7 Hz), 144.5, 136.6, 134.9, 132.4 (d, J = 2.2 Hz),
132.1, 132.0, 130.8 (d, J = 8.3 Hz), 129.1, 129.0, 129.0, 128.6, 128.5,
124.2 (d, J = 3.2 Hz), 122.8 (d, J = 12.0 Hz), 122.5, 115.2 (d, J = 20.7
Hz), 87.6, 84.4, 50.9 (d, J = 3.0 Hz), 21.7; 19F NMR (377 MHz,
CDCl3) δ −117.1; HRMS (ESI-TOF) m/z calcd for C29H22FNO3SNa
(M + Na)+ 506.1202, found 506.1209.
N-(3-Phenyl-1-o-tolylprop-2-ynyl)-N-tosylbenzamide (15a).
White solid, 0.7 g, 29% yield, mp 135−137 °C; 1H NMR (400
MHz, CDCl3) δ 8.02−7.94 (m, 1H), 7.64 (d, J = 7.3 Hz, 2H), 7.50 (d,
J = 8.5 Hz, 4H), 7.44 (t, J = 7.4 Hz, 1H), 7.38−7.28 (m, 5H), 7.17 (dd,
J = 5.6, 3.5 Hz, 2H), 7.07 (d, J = 8.2 Hz, 2H), 7.03−6.96 (m, 1H), 6.34
(s, 1H), 2.28 (s, 3H), 2.20 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
171.5, 144.5, 136.5, 136.1, 135.1, 132.9, 132.2, 131.8, 131.8, 130.5,
129.1, 128.8, 128.8, 128.8, 128.4, 128.2, 125.9, 122.6, 87.4, 86.1, 53.9,
21.6, 19.5; HRMS (ESI-TOF) m/z calcd for C30H25NO3SNa (M +
Na)+ 502.1453, found 502.1462.
1
97−99 °C; H NMR (500 MHz, CDCl3) δ 7.98 (d, J = 8.4 Hz, 2H),
7.60−7.54 (m, 2H), 7.49 (d, J = 7.5 Hz, 1H), 7.39 (t, J = 7.7 Hz, 2H),
7.36−7.28 (m, 5H), 7.26 (d, J = 8.4 Hz, 2H), 4.80 (s, 2H), 2.39 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 170.8, 145.0, 136.0, 134.4,
131.9, 131.8, 129.5, 129.1, 128.9, 128.5, 128.4, 128.0, 122.2, 85.1, 83.9,
38.9, 21.7; HRMS (ESI-TOF) m/z calcd for C23H19NO3SNa (M +
Na)+ 412.0983, found 412.0986.
N-(1,3-Diphenylprop-2-ynyl)-N-tosylacetamide (18a). White crys-
tals, 1.1 g, 55% yield, mp 146−147 °C; 1H NMR (500 MHz, CDCl3) δ
7.98 (d, J = 8.4 Hz, 2H), 7.70 (dd, J = 8.4, 1.0 Hz, 2H), 7.48−7.30 (m,
10H), 7.04 (s, 1H), 2.44 (s, 3H), 2.12 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 170.2, 145.0, 137.0, 136.8, 131.9, 129.8, 129.1, 128.9, 128.6,
128.4, 128.3, 127.0, 122.2, 87.5, 84.7, 52.5, 25.7, 21.8; HRMS (ESI-
TOF) m/z calcd for C24H21NO3SNa (M + Na)+ 426.1140, found
426.1147.
N-(3-Cyclohexyl-1-phenylprop-2-ynyl)-N-tosylacetamide (19a).
White solid, 0.8 g, 39% yield, mp 116−117 °C; 1H NMR (500
MHz, CDCl3) δ 7.99−7.95 (m, 2H), 7.65−7.61 (m, 2H), 7.42−7.37
(m, 2H), 7.36−7.29 (m, 3H), 6.82 (d, J = 1.0 Hz, 1H), 2.54 (s, 1H),
2.45 (s, 3H), 1.99 (s, 3H), 1.83 (s, 2H), 1.71 (s, 2H), 1.51 (s, 3H),
1.35 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 170.6, 144.8, 137.5,
136.9, 129.5, 128.8, 128.4, 128.0, 126.9, 92.6, 75.7, 52.2, 32.6, 32.6,
29.1, 25.9, 25.7, 24.8, 21.8; HRMS (ESI-TOF) m/z calcd for
C24H27NO3SNa (M + Na)+ 432.1609, found 432.1600.
N-(1-Phenyl-3-p-tolylprop-2-ynyl)-N-tosylacetamide (20a). White
solid, 1.2 g, 57% yield, mp 109−110 °C; 1H NMR (500 MHz, CDCl3)
δ 8.03−7.96 (m, 2H), 7.76−7.67 (m, 2H), 7.42 (t, J = 7.6 Hz, 2H),
7.39−7.31 (m, 5H), 7.17 (d, J = 7.8 Hz, 2H), 7.05 (s, 1H), 2.43 (s,
3H), 2.38 (s, 3H), 2.11 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
170.2, 144.9, 139.3, 137.0, 136.7, 131.8, 129.7, 129.3, 128.8, 128.3,
128.2, 126.9, 119.0, 87.6, 83.9, 52.4, 25.6, 21.7, 21.6; HRMS (ESI-
TOF) m/z calcd for C25H23NO3SNa (M + Na)+ 440.1296, found
440.1303.
N-(1-Phenyl-3-o-tolylprop-2-ynyl)-N-tosylacetamide (21a). White
solid, 1.0 g, 48% yield, mp 86−88 °C; 1H NMR (500 MHz, CDCl3) δ
7.96 (d, J = 8.4 Hz, 2H), 7.75−7.68 (m, 2H), 7.41 (dd, J = 10.9, 4.4
Hz, 3H), 7.35−7.28 (m, 3H), 7.23 (ddd, J = 17.0, 7.5, 0.9 Hz, 2H),
7.16 (dd, J = 10.7, 4.2 Hz, 1H), 7.07 (s, 1H), 2.41 (d, J = 8.8 Hz, 6H),
2.11 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 170.0, 145.0, 140.5,
137.0, 136.7, 132.3, 129.7, 129.0, 128.8, 128.3, 128.2, 127.0, 125.7,
121.9, 88.3, 86.4, 52.6, 25.7, 21.7, 20.9; HRMS (ESI-TOF) m/z calcd
for C25H23NO3SNa (M + Na)+ 440.1296, found 440.1281.
N-(3-Phenyl-1-o-tolylprop-2-ynyl)-N-tosylacetamide (22a). White
solid, 0.9 g, 43% yield, mp 160−161 °C; 1H NMR (500 MHz, CDCl3)
δ 8.00 (dd, J = 5.2, 4.0 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.51−7.45
(m, 2H), 7.38−7.31 (m, 3H), 7.29−7.25 (m, 2H), 7.23−7.19 (m, 2H),
7.17−7.13 (m, 1H), 7.06 (s, 1H), 2.38 (d, J = 1.6 Hz, 6H), 2.19 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 170.2, 144.9, 136.8, 133.7,
131.9, 131.1, 130.9, 129.6, 128.9, 128.8, 128.5, 128.3, 125.9, 122.4,
87.3, 85.7, 51.3, 25.9, 21.7, 20.0; HRMS (ESI-TOF) m/z calcd for
C25H23NO3SNa (M + Na)+ 440.1296, found 440.1281.
N-(4-Methyl-1-phenylpent-1-yn-3-yl)-N-tosylbenzamide (16a).
White solid, 1.4 g, 65% yield, mp 152−153 °C; 1H NMR (400
MHz, CDCl3) δ 7.82 (d, J = 7.9 Hz, 2H), 7.51 (d, J = 7.9 Hz, 2H),
7.46 (s, 1H), 7.43−7.38 (m, 2H), 7.34 (dd, J = 13.6, 6.4 Hz, 5H), 7.20
(d, J = 8.1 Hz, 2H), 4.70 (d, J = 10.4 Hz, 1H), 2.69 (qt, J = 13.1, 6.6
Hz, 1H), 2.34 (s, 3H), 1.15 (d, J = 6.6 Hz, 3H), 1.10 (d, J = 6.6 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 171.0, 144.8, 136.4, 135.4,
131.8, 131.7, 129.4, 128.8, 128.5, 128.4, 128.3, 128.2, 122.9, 86.9, 85.2,
59.8, 32.6, 21.7, 21.1, 19.9; HRMS (ESI-TOF) m/z calcd for
C26H25NO3SNa (M + Na)+ 454.1435, found 454.1440.
N-(3-Phenylprop-2-ynyl)-N-tosylbenzamide (17a). NaH (60%, 20
mg, 0.5 mmol) was added to a solution of 4-methyl-N-(3-phenylprop-
2-ynyl)benzenesulfonamide (71 mg, 0.25 mmol) in dry THF (2 mL),
and the mixture was stirred at rt for 1 h. The resulting solvent was
cooled to 0 °C in an ice−water bath, and benzoyl chloride (42 mg, 0.3
mmol) was added to it slowly. Then the reaction mixture was allowed
N-(1-(2-Chlorophenyl)-3-phenylprop-2-ynyl)-N-tosylacetamide
1
(23a). White solid, 1.3 g, 59% yield, mp 160−161 °C; H NMR (500
MHz, CDCl3) δ 8.22−8.17 (m, 1H), 7.64 (d, J = 8.3 Hz, 2H), 7.58−
7.50 (m, 2H), 7.40−7.34 (m, 4H), 7.31 (dd, J = 4.9, 1.2 Hz, 2H),
7.23−7.16 (m, 2H), 7.08 (s, 1H), 2.38 (s, 3H), 2.35 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 169.8, 144.8, 137.1, 133.9, 133.4, 133.3, 132.0,
130.0, 129.7, 129.6, 128.9, 128.5, 127.9, 126.6, 122.3, 87.0, 84.9, 50.8,
25.4, 21.6; HRMS (ESI-TOF) m/z calcd for C24H20ClNO3SNa (M +
Na)+ 460.0750, found 460.0757.
N-(1-(2-Fluorophenyl)-3-phenylprop-2-ynyl)-N-tosylacetamide
1
(24a). White solid, 1.4 g, 65% yield, mp 119−120 °C; H NMR (500
MHz, CDCl3) δ 8.01 (td, J = 7.8, 1.0 Hz, 1H), 7.82 (d, J = 8.3 Hz,
2H), 7.55−7.46 (m, 2H), 7.41−7.30 (m, 4H), 7.25−7.18 (m, 3H),
7.04 (ddd, J = 10.5, 8.2, 0.9 Hz, 1H), 2.40 (d, J = 7.1 Hz, 3H), 2.26 (s,
4899
dx.doi.org/10.1021/jo4004635 | J. Org. Chem. 2013, 78, 4895−4904

The Journal of Organic Chemistry
Article
3H); 13C NMR (126 MHz, CDCl3) δ 169.4, 160.6 (d, J = 250.1 Hz),
144.9, 137.1, 131.9, 130.5 (d, J = 8.4 Hz), 129.7, 129.0, 128.5, 128.1,
123.9 (d, J = 3.3 Hz), 123.6 (d, J = 11.9 Hz), 122.2, 115.6 (d, J = 20.9
Hz), 87.1, 84.1, 47.8, 25.4, 21.6; HRMS (ESI-TOF) m/z calcd for
C24H20FNO3SNa (M + Na)+ 444.1046, found 444.1061.
N-(1-Cyclopropyl-3-phenylprop-2-ynyl)-N-tosylacetamide (25a).
White solid, 770 mg, 42% yield, mp 84−85 °C; 1H NMR (500
MHz, CDCl3) δ 7.91 (d, J = 8.4 Hz, 2H), 7.36 (dt, J = 6.0, 2.5 Hz,
2H), 7.32−7.21 (m, 5H), 4.88 (d, J = 8.8 Hz, 1H), 2.39 (s, 3H), 2.36
(s, 3H), 1.96−1.86 (m, 1H), 0.81−0.74 (m, 1H), 0.68−0.60 (m, 2H),
0.60−0.54 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 169.7, 144.8,
137.1, 131.7, 129.8, 128.5, 128.3, 127.6, 122.5, 86.1, 84.0, 55.2, 25.7,
21.5, 16.5, 6.5, 4.8; HRMS (ESI-TOF) m/z calcd for C21H21NO3SNa
(M + Na)+ 390.1140, found 390.1144.
N-(1-Phenyl-3-p-tolylprop-2-ynyl)-N-(phenylsulfonyl)benzamide
1
(32a). White solid, 950 mg, 41% yield, mp 118−119 °C; H NMR
(500 MHz, CDCl3) δ 7.92 (d, J = 7.6 Hz, 2H), 7.55 (dd, J = 16.1, 7.8
Hz, 3H), 7.47−7.35 (m, 7H), 7.32−7.22 (m, 5H), 7.18 (d, J = 7.8 Hz,
2H), 6.58 (s, 1H), 2.39 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
171.3, 139.3, 139.1, 136.2, 135.1, 133.7, 131.8, 131.7, 129.2, 128.9,
128.8, 128.5, 128.4, 128.3, 128.0, 119.3, 87.9, 84.1, 54.7, 21.6; HRMS
(ESI-TOF) m/z calcd for C29H23NO3SNa (M + Na)+ 488.1296; found
488.1312.
N-(1,3-Diphenylprop-2-ynyl)-N-(methylsulfonyl)benzamide
1
(33a). White solid, 290 mg, 15% yield, mp 161−162 °C; H NMR
(500 MHz, CDCl3) δ 7.64−7.59 (m, 2H), 7.57−7.46 (m, 5H), 7.43−
7.28 (m, 8H), 6.40 (s, 1H), 3.23 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 173.1, 135.9, 134.3, 132.5, 132.0, 129.2, 128.8, 128.7, 128.7,
128.6, 128.5, 128.1, 122.1, 88.3, 84.3, 55.3, 43.1; HRMS (ESI-TOF)
m/z calcd for C23H19NO3SNa (M + Na)+ 412.0983, found 412.1000.
N-(Methylsulfonyl)-N-(1-phenyl-3-p-tolylprop-2-ynyl)benzamide
N-(1-(Furan-2-yl)-3-phenylprop-2-ynyl)-N-tosylacetamide (26a).
1
Yellow gum, 236 mg, 12% yield; H NMR (500 MHz, CDCl3) δ
7.95−7.87 (m, 2H), 7.51−7.44 (m, 2H), 7.42−7.40 (m, 1H), 7.38−
7.30 (m, 5H), 7.01 (s, 1H), 6.65−6.59 (m, 1H), 6.40 (dd, J = 3.3, 1.8
Hz, 1H), 2.43 (s, 3H), 2.25 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
170.0, 149.5, 145.0, 143.0, 136.9, 132.0, 129.7, 129.2, 128.6, 128.5,
122.0, 111.0, 109.9, 86.0, 83.2, 46.8, 25.2, 21.8; HRMS (ESI-TOF) m/
z calcd for C22H19NO4SNa (M + Na)+ 416.0932, found 416.0923.
N-(1,3-Diphenylprop-2-ynyl)-N-tosylcyclopropanecarboxamide
(27a). White solid, 1.5 g, 71% yield, mp 117−118 °C; 1H NMR (500
MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 2H), 7.71 (d, J = 7.6 Hz, 2H),
7.48 (d, J = 7.3 Hz, 2H), 7.42 (d, J = 7.5 Hz, 2H), 7.40−7.29 (m, 6H),
7.11 (s, 1H), 2.43 (s, 3H), 2.00 (dd, J = 4.5, 3.0 Hz, 1H), 0.93 (dd, J =
4.8, 2.6 Hz, 1H), 0.83−0.68 (m, 2H), 0.49−0.40 (m, 1H); 13C NMR
(126 MHz, CDCl3) δ 174.1, 144.7, 137.4, 137.1, 131.9, 129.6, 129.0,
128.9, 128.6, 128.3, 128.1, 126.8, 122.2, 87.4, 85.1, 52.4, 21.7, 16.0,
10.8, 10.7; HRMS (ESI-TOF) m/z calcd for C26H23NO3SNa (M +
Na)+ 452.1296, found 452.1279.
1
(34a). White solid, 342 mg, 17% yield, mp 139−140 °C; H NMR
(500 MHz, CDCl3) δ 7.61 (dt, J = 8.4, 1.4 Hz, 2H), 7.55−7.46 (m,
3H), 7.45−7.40 (m, 2H), 7.37−7.28 (m, 5H), 7.19 (d, J = 7.8 Hz,
2H), 6.40 (s, 1H), 3.25 (s, 3H), 2.39 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 173.1, 139.4, 136.1, 134.3, 132.4, 131.9, 129.3, 128.8, 128.6,
128.5, 128.4, 128.1, 119.0, 88.5, 83.6, 55.3, 43.0, 21.6; HRMS (ESI-
TOF) m/z calcd for C24H21NO3SNa (M + Na)+ 426.1140, found
426.1151.
N-(3-(4-Fluorophenyl)-1-phenylprop-2-ynyl)-N-(methylsulfonyl)-
benzamide (35a). White solid, 223 mg, 11% yield, mp 170−171 °C;
1H NMR (500 MHz, CDCl3) δ 7.66−7.60 (m, 2H), 7.55−7.49 (m,
5H), 7.38−7.31 (m, 5H), 7.11−7.03 (m, 2H), 6.37 (s, 1H), 3.18 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 172.9, 163.1 (d, J = 250.6 Hz),
135.8, 134.2, 134.0 (d, J = 8.5 Hz), 132.6, 128.8, 128.7, 128.7, 128.5,
128.1, 118.2 (d, J = 3.5 Hz), 115.9 (d, J = 22.2 Hz), 87.2, 84.2, 55.3,
43.1; 19F NMR (377 MHz, CDCl3) δ −110.1 (d, J = 0.9 Hz); HRMS
(ESI-TOF) m/z calcd for C23H18FNO3SNa (M + Na)+ 430.0889,
found 430.0883.
N-(1,3-Diphenylprop-2-ynyl)-N-tosylcyclobutanecarboxamide
1
(28a). White solid, 758 mg, 34% yield, mp 146−147 °C; H NMR
(500 MHz, CDCl3) δ 7.98 (d, J = 8.4 Hz, 2H), 7.67 (dd, J = 8.3, 1.0
Hz, 2H), 7.49−7.40 (m, 4H), 7.40−7.30 (m, 6H), 6.93 (s, 1H), 3.51
(p, J = 8.1 Hz, 1H), 2.43 (s, 3H), 2.18 (dt, J = 18.1, 8.9 Hz, 1H), 2.05−
1.92 (m, 2H), 1.77−1.64 (m, 2H), 1.37−1.25 (m, 1H); 13C NMR
(126 MHz, CDCl3) δ 175.4, 144.8, 137.3, 137.1, 131.9, 129.7, 129.1,
128.9, 128.6, 128.3, 128.2, 126.8, 122.2, 87.3, 85.0, 52.3, 40.1, 25.3,
21.8, 17.7; HRMS (ESI-TOF) m/z calcd for C27H25NO3SNa (M +
Na)+ 466.1453, found 466.1447.
N-(1,3-Diphenylprop-2-ynyl)-N-(methylsulfonyl)acetamide (36a).
White solid, 337 mg, 21% yield, mp 102−103 °C; H NMR (500
MHz, CDCl3) δ 7.68−7.62 (m, 2H), 7.54 (dt, J = 4.0, 2.3 Hz, 2H),
7.46−7.33 (m, 6H), 6.90 (s, 1H), 3.45 (s, 3H), 2.23 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 171.9, 136.7, 132.0, 129.3, 129.0, 128.6, 128.4,
126.8, 121.7, 87.8, 84.1, 51.6, 43.0, 25.7; HRMS (ESI-TOF) m/z calcd
for C18H17NO3SNa (M + Na)+ 350.0827, found 350.0836.
1
N-(3-(4-Fluorophenyl)-1-phenylprop-2-ynyl)-N-(methylsulfonyl)-
acetamide (37a). White solid, 397 mg, 23% yield, mp 91−92 °C; 1H
NMR (500 MHz, CDCl3) δ 7.65−7.60 (m, 2H), 7.54−7.49 (m, 2H),
7.45−7.39 (m, 2H), 7.37−7.31 (m, 1H), 7.08−7.03 (m, 2H), 6.88 (s,
1H), 3.42 (s, 3H), 2.23 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
171.6, 163.0 (d, J = 250.9 Hz), 136.6, 134.0 (d, J = 8.5 Hz), 128.9,
128.4, 126.7, 117.8 (d, J = 3.4 Hz), 115.9 (d, J = 22.2 Hz), 86.6, 84.0,
51.4, 43.0, 25.6; 19F NMR (377 MHz, CDCl3) δ −109.7; HRMS (ESI-
TOF) m/z calcd for C18H16FNO3SNa (M + Na)+ 368.0733, found
368.0729.
General Procedure for the Preparation of Oxazoles b. A 10
mL vial equipped with a magnetic stirrer was charged with propargylic
amide a (0.1 mmol), DBU (1.5 mg, 10 mol %), and CH3CN (1 mL).
The mixture was stirred at rt for 7 h under air. The crude mixture was
concentrated and purified by flash column chromatography to give the
desired product b.
2,4-Diphenyl-5-(phenyl(tosyl)methyl)oxazole (1b). White solid, 46
mg, 98% yield, mp 156−157 °C; 1H NMR (500 MHz, CDCl3) δ 8.12
(ddd, J = 5.6, 3.0, 1.5 Hz, 2H), 7.70−7.62 (m, 2H), 7.55−7.49 (m,
3H), 7.49−7.35 (m, 10H), 7.13 (d, J = 8.0 Hz, 2H), 5.70 (s, 1H), 2.39
(s, 3H); 13C NMR (126 MHz, CDCl3) δ 161.9, 145.2, 142.4, 138.5,
134.5, 131.0, 130.9, 130.8, 130.4, 129.5, 129.5, 129.3, 129.0, 129.0,
128.8, 128.8, 127.9, 127.1, 126.9, 68.7, 21.8; HRMS (ESI-TOF) m/z
calcd for C29H23NO3SNa (M + Na)+ 488.1296, found 488.1288.
4-Phenyl-5-(phenyl(tosyl)methyl)-2-o-tolyloxazole (2b). White
solid, 46 mg, 96% yield, mp 143−145 °C; 1H NMR (500 MHz,
CDCl3) δ 8.09−8.03 (m, 1H), 7.74−7.66 (m, 2H), 7.51−7.46 (m,
2H), 7.44 (d, J = 8.3 Hz, 2H), 7.43−7.32 (m, 9H), 7.12 (d, J = 8.0 Hz,
Benzyl 1,3-Diphenylprop-2-ynyl(tosyl)carbamate (29a). Colorless
1
crystals, 767 mg, 31% yield, mp 97−99 °C; H NMR (500 MHz,
CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 7.3 Hz, 2H), 7.38−7.26
(m, 8H), 7.22 (d, J = 7.2 Hz, 1H), 7.19−7.12 (m, 4H), 6.98 (d, J = 7.3
Hz, 2H), 6.90 (s, 1H), 5.02−4.90 (m, 2H), 2.35 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 151.4, 144.7, 137.1, 136.3, 134.4, 131.9, 129.3,
128.8, 128.6, 128.4, 128.3, 128.0, 127.3, 122.3, 86.7, 84.7, 68.9, 53.1,
21.6; HRMS (ESI-TOF) m/z calcd for C30H25NO4SNa (M + Na)+
518.1402, found 518.1405.
N-(1,3-Diphenylprop-2-ynyl)-N-(phenylsulfonyl)benzamide
1
(30a). White solid, 670 mg, 30% yield, mp 146−147 °C; H NMR
(500 MHz, CDCl3) δ 7.89 (d, J = 8.3 Hz, 2H), 7.55 (dd, J = 13.2, 7.4
Hz, 3H), 7.49−7.34 (m, 10H), 7.32−7.22 (m, 5H), 6.57 (s, 1H); 13C
NMR (126 MHz, CDCl3) δ 171.3, 139.3, 136.2, 135.1, 133.7, 132.0,
131.8, 129.0, 128.8, 128.5, 128.5, 128.4, 128.0, 122.4, 87.8, 84.8, 54.6;
HRMS (ESI-TOF) m/z calcd for C28H21NO3SNa (M + Na)+
474.1140, found 474.1129.
N-(3-(4-Fluorophenyl)-1-phenylprop-2-ynyl)-N-(phenylsulfonyl)-
benzamide (31a). White solid, 1.1 g, 49% yield, mp 132−133 °C; 1H
NMR (500 MHz, CDCl3) δ 7.83 (dd, J = 8.4, 1.1 Hz, 2H), 7.58−7.49
(m, 3H), 7.43 (ddd, J = 14.3, 7.2, 1.7 Hz, 7H), 7.30−7.23 (m, 5H),
7.04 (dd, J = 12.1, 5.3 Hz, 2H), 6.53 (s, 1H); 13C NMR (126 MHz,
CDCl3) δ 171.2, 163.0 (d, J = 250.6 Hz), 139.3, 136.0, 135.1, 133.9 (d,
J = 8.4 Hz), 133.8, 131.9, 128.9, 128.8, 128.6, 128.6, 128.4, 128.1,
118.5 (d, J = 3.3 Hz), 115.8 (d, J = 22.1 Hz), 86.7, 84.6, 54.6; 19F
NMR (377 MHz, CDCl3) δ −110.5; HRMS (ESI-TOF) m/z calcd for
C28H20FNO3SNa (M + Na)+ 492.1046, found 492.1042.
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2H), 5.72 (s, 1H), 2.82 (s, 3H), 2.37 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 162.4, 145.2, 142.0, 138.0, 138.0, 134.6, 131.9, 131.1, 130.8,
130.6, 130.4, 129.6, 129.5, 129.4, 129.1, 129.0, 128.8, 128.7, 127.8,
126.2, 126.1, 68.6, 22.3, 21.7; HRMS (ESI-TOF) m/z calcd for
C30H25NO3SNa (M + Na)+ 502.1453, found 502.1435.
4-Phenyl-5-(phenyl(tosyl)methyl)-2-m-tolyloxazole (3b). White
solid, 47 mg, 98% yield, mp 56−57 °C; 1H NMR (500 MHz,
CDCl3) δ 7.97−7.88 (m, 2H), 7.71−7.60 (m, 2H), 7.49−7.36 (m,
11H), 7.33 (d, J = 7.6 Hz, 1H), 7.14 (d, J = 7.9 Hz, 2H), 5.71 (s, 1H),
2.47 (s, 3H), 2.39 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 162.1,
145.2, 142.3, 138.8, 138.4, 134.5, 131.9, 130.9, 130.8, 130.4, 129.5,
129.5, 129.3, 129.0, 128.9, 128.8, 128.8, 127.9, 127.4, 127.0, 124.1,
68.7, 21.8, 21.5; HRMS (ESI-TOF) m/z calcd for C30H25NO3SNa (M
+ Na)+ 502.1453, found 502.1472.
4-Phenyl-5-(phenyl(tosyl)methyl)-2-p-tolyloxazole (4b). White
solid, 46 mg, 97% yield, mp 149−151 °C; 1H NMR (500 MHz,
CDCl3) δ 8.00 (d, J = 8.0 Hz, 2H), 7.72−7.63 (m, 2H), 7.48−7.37 (m,
10H), 7.32 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 8.1 Hz, 2H), 5.69 (s, 1H),
2.45 (s, 3H), 2.39 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 162.1,
145.1, 142.3, 141.4, 138.1, 134.5, 131.0, 130.8, 130.5, 129.7, 129.5,
129.5, 129.3, 129.0, 128.8, 128.7, 127.9, 126.9, 124.4, 68.7, 21.8, 21.7;
HRMS (ESI-TOF) m/z calcd for C30H25NO3SNa (M + Na)+
502.1453, found 502.1472.
m/z calcd for C30H22F3NO3SNa (M + Na)+ 556.1170, found
556.1180.
4-Phenyl-5-(phenyl(tosyl)methyl)-2-(4-(trifluoromethyl)phenyl)-
1
oxazole (10b). White solid, 53 mg, 99% yield, mp 189−191 °C; H
NMR (500 MHz, CDCl3) δ 8.24 (d, J = 8.2 Hz, 2H), 7.78 (d, J = 8.2
Hz, 2H), 7.69−7.61 (m, 2H), 7.49 (d, J = 6.6 Hz, 2H), 7.42 (dt, J =
11.5, 5.8 Hz, 8H), 7.14 (d, J = 8.0 Hz, 2H), 5.70 (s, 1H), 2.39 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 160.5, 145.4, 142.8, 139.3, 134.5,
132.6 (q, J = 32.8 Hz), 130.7, 130.6, 130.3, 130.2, 129.6, 129.6, 129.2,
129.1, 129.0, 128.9, 127.9, 127.1, 126.1 (q, J = 3.7 Hz), 124.0 (q, J =
272.4 Hz), 68.6, 21.8; 19F NMR (377 MHz, CDCl3) δ −63.5; HRMS
(ESI-TOF) m/z calcd for C30H22F3NO3SNa (M + Na)+ 556.1170,
found 556.1178.
5-((4-Fluorophenyl)(tosyl)methyl)-2,4-diphenyloxazole (11b).
1
White solid, 43 mg, 90% yield, mp 70−72 °C; H NMR (500 MHz,
CDCl3) δ 8.15−8.04 (m, 2H), 7.68−7.60 (m, 2H), 7.54−7.49 (m,
3H), 7.47−7.34 (m, 7H), 7.13 (d, J = 8.1 Hz, 2H), 7.09 (dd, J = 11.9,
5.3 Hz, 2H), 5.66 (s, 1H), 2.38 (s, 3H); 13C NMR (126 MHz, CDCl3)
δ 163.5 (d, J = 249.7 Hz), 161.9, 145.4, 142.5, 138.2, 134.3, 132.6 (d, J
= 8.4 Hz), 131.1, 130.8, 129.7, 129.2, 129.1, 128.9, 127.8, 127.0, 126.9,
126.3 (d, J = 3.0 Hz), 116.1 (d, J = 21.7 Hz), 67.8, 21.8; 19F NMR
(377 MHz, CDCl3) δ −112.0; HRMS (ESI-TOF) m/z calcd for
C29H22FNO3SNa (M + Na)+ 506.1202, found 506.1194.
2-(3-Chlorophenyl)-4-phenyl-5-(phenyl(tosyl)methyl)oxazole
(5b). White solid, 46 mg, 93% yield, mp 156−158 °C; 1H NMR (500
MHz, CDCl3) δ 8.04−8.00 (m, 2H), 7.65−7.57 (m, 2H), 7.52−7.38
(m, 12H), 7.20−7.11 (m, 2H), 5.72 (s, 1H), 2.41 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 160.5, 145.4, 142.6, 139.1, 135.2, 134.3, 131.0,
130.7, 130.4, 130.4, 129.6, 129.4, 129.0, 129.0, 128.9, 128.7, 127.9,
126.7, 125.0, 68.7, 21.8; HRMS (ESI-TOF) m/z calcd for
C29H22ClNO3SNa (M + Na)+ 522.0907, found 522.0892.
2-(4-Chlorophenyl)-4-phenyl-5-(phenyl(tosyl)methyl)oxazole
(6b). White solid, 48 mg, 96% yield, mp 148−150 °C; 1H NMR (500
MHz, CDCl3) δ 8.08−8.03 (m, 2H), 7.52−7.45 (m, 4H), 7.45−7.36
(m, 8H), 7.13 (d, J = 7.9 Hz, 2H), 5.69 (s, 1H), 2.39 (s, 3H); 13C
NMR (126 MHz, CDCl3) δ 160.9, 145.3, 142.5, 138.7, 137.2, 134.5,
130.7, 130.7, 130.4, 129.6, 129.4, 129.2, 129.0, 128.9, 128.9, 128.1,
127.9, 125.6, 68.6, 21.8; HRMS (ESI-TOF) m/z calcd for
C29H22ClNO3SNa (M + Na)+ 522.0907, found 522.0893.
2-(3-Fluorophenyl)-4-phenyl-5-(phenyl(tosyl)methyl)oxazole
(7b). White solid, 47 mg, 97% yield, mp 151−153 °C; 1H NMR (500
MHz, CDCl3) δ 7.95−7.89 (m, 1H), 7.76 (ddd, J = 9.4, 2.4, 1.6 Hz,
1H), 7.66−7.60 (m, 2H), 7.53−7.46 (m, 3H), 7.46−7.36 (m, 8H),
7.21 (tdd, J = 8.4, 2.6, 0.7 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 5.70 (s,
1H), 2.40 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 164.1, 161.4 (d, J =
185.5 Hz), 145.4, 142.6, 138.9, 134.4, 130.8 (d, J = 8.1 Hz), 130.7,
130.4, 129.6, 129.4, 129.0, 129.0, 128.9, 128.9, 127.9, 122.6 (d, J = 2.9
Hz), 118.0 (d, J = 21.3 Hz), 113.8 (d, J = 23.9 Hz), 68.7, 21.8; 19F
NMR (377 MHz, CDCl3) δ −112.4; HRMS (ESI-TOF) m/z calcd for
C29H22FNO3SNa (M + Na)+ 506.1202, found 506.1205.
2-(4-Fluorophenyl)-4-phenyl-5-(phenyl(tosyl)methyl)oxazole
(8b). White solid, 46 mg, 95% yield, mp 176−177 °C; 1H NMR (500
MHz, CDCl3) δ 8.17−8.06 (m, 2H), 7.67−7.59 (m, 2H), 7.49−7.32
(m, 10H), 7.23−7.16 (m, 2H), 7.12 (d, J = 8.0 Hz, 2H), 5.67 (s, 1H),
2.37 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 164.6 (d, J = 252.1 Hz),
161.1, 145.2, 142.4, 138.5, 134.5, 134.5, 130.8 (d, J = 8.1 Hz), 130.7,
130.4, 129.6, 129.5, 129.2, 129.1, 129.0, 128.9, 123.5 (d, J = 3.0 Hz),
116.3 (d, J = 22.2 Hz), 68.6, 21.8; 19F NMR (377 MHz, CDCl3) δ
−105.2; HRMS (ESI-TOF) m/z calcd for C29H22FNO3SNa (M +
Na)+ 506.1202, found 506.1217.
2,4-Diphenyl-5-(p-tolyl(tosyl)methyl)oxazole (12b). White solid,
40 mg, 83% yield, mp 59−60 °C; 1H NMR (500 MHz, CDCl3) δ 8.11
(ddd, J = 5.5, 3.0, 1.5 Hz, 2H), 7.56 (d, J = 8.2 Hz, 2H), 7.51 (tt, J =
4.1, 1.8 Hz, 3H), 7.48−7.43 (m, 4H), 7.43−7.36 (m, 3H), 7.22 (d, J =
7.9 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H), 5.67 (s, 1H), 2.38 (d, J = 4.0 Hz,
6H); 13C NMR (126 MHz, CDCl3) δ 161.8, 145.1, 142.2, 139.6,
138.7, 134.6, 131.0, 131.0, 130.6, 129.7, 129.5, 129.3, 129.0, 128.8,
128.7, 127.9, 127.3, 127.1, 126.9, 68.4, 21.8, 21.4; HRMS (ESI-TOF)
m/z calcd for C30H25NO3SNa (M + Na)+ 502.1453, found 502.1462.
4-(2-Chlorophenyl)-2-phenyl-5-(phenyl(tosyl)methyl)oxazole
(13b). Yellow gum, 48 mg, 96% yield; 1H NMR (500 MHz, CDCl3) δ
8.11 (ddd, J = 5.1, 2.4, 1.5 Hz, 2H), 7.75−7.66 (m, 2H), 7.56−7.47
(m, 3H), 7.45−7.35 (m, 6H), 7.32 (td, J = 7.7, 1.7 Hz, 1H), 7.23 (dt, J
= 7.5, 1.4 Hz, 1H), 7.15−7.07 (m, 3H), 5.45 (s, 1H), 2.39 (s, 3H); 13C
NMR (126 MHz, CDCl3) δ 162.0, 145.0, 140.0, 139.6, 134.5, 133.2,
132.0, 131.0, 130.9, 130.2, 129.9, 129.6, 129.5, 129.3, 129.0, 128.9,
128.7, 126.8, 126.8, 126.7, 68.7, 21.6; HRMS (ESI-TOF) m/z calcd for
C29H22ClNO3SNa (M + Na)+ 522.0907, found 522.0890.
4-(2-Fluorophenyl)-2-phenyl-5-(phenyl(tosyl)methyl)oxazole
1
(14b). White solid, 46 mg, 96% yield, mp 72−73 °C; H NMR (500
MHz, CDCl3) δ 8.17−8.08 (m, 2H), 7.78 (dd, J = 6.7, 2.9 Hz, 2H),
7.57−7.48 (m, 3H), 7.47−7.31 (m, 7H), 7.16 (dt, J = 8.7, 4.3 Hz, 1H),
7.12−7.04 (m, 3H), 5.67 (d, J = 1.5 Hz, 1H), 2.35 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 162.4, 159.2 (d, J = 248.0 Hz), 145.0, 140.2,
136.4, 134.5, 131.4 (d, J = 2.7 Hz), 131.1, 130.9, 130.6 (d, J = 8.3 Hz),
129.9, 129.5, 129.5, 129.0, 128.9, 126.9, 126.9, 124.4 (d, J = 3.2 Hz),
118.6 (d, J = 14.1 Hz), 115.9 (d, J = 22.2 Hz), 110.1, 68.7 (d, J = 7.1
Hz), 21.7; 19F NMR (377 MHz, CDCl3) δ −113.5; HRMS (ESI-
TOF) m/z calcd for C29H22FNO3SNa (M + Na)+ 506.1202, found
506.1208.
2-Phenyl-5-(phenyl(tosyl)methyl)-4-o-tolyloxazole (15b). White
solid, 46 mg, 97% yield, mp 66−68 °C; 1H NMR (500 MHz,
CDCl3) δ 8.19−8.08 (m, 2H), 7.67−7.57 (m, 2H), 7.56−7.48 (m,
3H), 7.47−7.43 (m, 2H), 7.43−7.35 (m, 3H), 7.31 (td, J = 7.5, 1.3 Hz,
1H), 7.24 (d, J = 7.6 Hz, 1H), 7.18 (dd, J = 12.2, 4.3 Hz, 3H), 6.97
(dd, J = 7.5, 1.2 Hz, 1H), 5.38 (s, 1H), 2.41 (s, 3H), 2.10 (s, 3H); 13C
NMR (126 MHz, CDCl3) δ 161.6, 145.1, 142.6, 139.5, 138.2, 134.9,
131.0, 130.8, 130.7, 130.4, 130.0, 129.7, 129.6, 129.4, 129.3, 129.3,
129.0, 129.0, 127.2, 126.8, 125.9, 68.1, 21.8, 20.0; HRMS (ESI-TOF)
m/z calcd for C30H25NO3SNa (M + Na)+ 502.1453, found 502.1448.
2-Methyl-4-phenyl-5-(phenyl(tosyl)methyl)oxazole (18b). White
solid, 36 mg, 89% yield, mp 168−169 °C; 1H NMR (500 MHz,
CDCl3) δ 7.57 (dd, J = 7.9, 1.6 Hz, 2H), 7.41−7.29 (m, 10H), 7.11 (d,
J = 7.9 Hz, 2H), 5.57 (s, 1H), 2.56 (s, 3H), 2.36 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 162.1, 145.1, 141.1, 138.0, 134.5, 130.9, 130.7,
130.4, 129.5, 129.4, 129.1, 128.9, 128.8, 128.6, 127.7, 68.4, 21.7, 14.3;
4-Phenyl-5-(phenyl(tosyl)methyl)-2-(3-(trifluoromethyl)phenyl)-
1
oxazole (9b). White solid, 50 mg, 94% yield, mp 152−153 °C; H
NMR (500 MHz, CDCl3) δ 8.33 (d, J = 7.8 Hz, 1H), 8.29 (s, 1H),
7.77 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 7.61 (dd, J = 7.6, 1.8
Hz, 2H), 7.56−7.49 (m, 2H), 7.48−7.35 (m, 8H), 7.16 (d, J = 8.0 Hz,
2H), 5.73 (s, 1H), 2.40 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
160.4, 145.5, 142.7, 139.3, 134.2, 131.7 (q, J = 32.9 Hz), 130.6, 130.6,
130.5, 130.0, 129.7, 129.6, 129.5, 129.5, 129.0, 129.0, 127.9, 127.9,
127.5 (q, J = 3.6 Hz), 123.9 (q, J = 272.6 Hz), 123.6 (q, J = 3.5 Hz),
68.8, 21.7; 19F NMR (377 MHz, CDCl3) δ −63.3; HRMS (ESI-TOF)
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HRMS (ESI-TOF) m/z calcd for C24H21NO3SNa (M + Na)+
426.1140, found 426.1136.
7.55 (dd, J = 7.8, 1.7 Hz, 2H), 7.42−7.29 (m, 10H), 7.13 (d, J = 8.0
Hz, 2H), 5.56 (s, 1H), 2.38 (s, 3H), 2.17 (tt, J = 8.2, 5.2 Hz, 1H),
1.23−1.08 (m, 4H); 13C NMR (126 MHz, CDCl3) δ 166.7, 145.1,
141.1, 137.0, 134.5, 131.0, 130.7, 130.5, 129.5, 129.4, 129.1, 128.9,
128.7, 128.5, 127.7, 68.5, 21.8, 9.2, 8.9, 8.8; HRMS (ESI-TOF) m/z
calcd for C26H23NO3SNa (M + Na)+ 452.1296, found 452.1308.
2-Cyclobutyl-4-phenyl-5-(phenyl(tosyl)methyl)oxazole (28b).
5-(Cyclohexyl(tosyl)methyl)-2-methyl-4-phenyloxazole (19b).
White solid, 21 mg, 51% yield, mp 180−181 °C; 1H NMR (500
MHz, CDCl3) δ 7.34 (d, J = 8.2 Hz, 2H), 7.28−7.21 (m, 3H), 7.09−
7.00 (m, 4H), 4.40 (d, J = 7.5 Hz, 1H), 2.70−2.60 (m, 1H), 2.51 (s,
3H), 2.33 (s, 3H), 2.27 (d, J = 12.8 Hz, 1H), 1.88 (d, J = 12.7 Hz, 1H),
1.75 (ddd, J = 29.9, 20.8, 8.2 Hz, 3H), 1.43−1.15 (m, 5H); 13C NMR
(126 MHz, CDCl3) δ 161.7, 144.6, 141.7, 138.7, 135.9, 130.7, 129.5,
128.4, 128.3, 128.0, 127.3, 68.3, 37.5, 32.4, 31.0, 26.3, 26.2, 26.1, 21.7,
14.2; HRMS (ESI-TOF) m/z calcd for C24H27NO3SNa (M + Na)+
432.1609, found 432.1599.
2-Methyl-4-phenyl-5-(p-tolyl(tosyl)methyl)oxazole (20b). White
solid, 38 mg, 91% yield, mp 56−57 °C; 1H NMR (500 MHz, CDCl3)
δ 7.48 (d, J = 8.2 Hz, 2H), 7.43−7.39 (m, 2H), 7.38−7.31 (m, 5H),
7.18 (d, J = 7.9 Hz, 2H), 7.12 (d, J = 7.9 Hz, 2H), 5.56 (s, 1H), 2.57
(s, 3H), 2.37 (d, J = 5.2 Hz, 6H); 13C NMR (126 MHz, CDCl3) δ
162.0, 145.0, 140.9, 139.5, 138.3, 134.6, 131.0, 130.6, 129.6, 129.5,
129.0, 128.7, 128.5, 127.6, 127.3, 68.1, 21.7, 21.4, 14.3; HRMS (ESI-
TOF) m/z calcd for C25H23NO3SNa (M + Na)+ 440.1296, found
440.1292.
2-Methyl-4-phenyl-5-(o-tolyl(tosyl)methyl)oxazole (21b). White
solid, 38 mg, 91% yield, mp 139−141 °C; 1H NMR (500 MHz,
CDCl3) δ 8.09 (dd, J = 7.6, 1.6 Hz, 1H), 7.47−7.41 (m, 2H), 7.39−
7.32 (m, 5H), 7.32−7.24 (m, 2H), 7.13 (t, J = 7.8 Hz, 3H), 5.96 (s,
1H), 2.58 (s, 3H), 2.38 (s, 3H), 2.10 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 162.2, 145.1, 141.1, 138.3, 137.6, 135.0, 131.0, 130.8, 130.8,
129.6, 129.3, 129.0, 128.7, 128.6, 127.6, 126.7, 63.2, 21.8, 19.8, 14.4;
HRMS (ESI-TOF) m/z calcd for C25H23NO3SNa (M + Na)+
440.1296, found 440.1302.
2-Methyl-5-(phenyl(tosyl)methyl)-4-o-tolyloxazole (22b). White
solid, 38 mg, 90% yield, mp 145−147 °C; 1H NMR (500 MHz,
CDCl3) δ 7.58−7.51 (m, 2H), 7.42−7.32 (m, 5H), 7.29−7.23 (m,
1H), 7.19 (d, J = 7.6 Hz, 1H), 7.14 (dd, J = 13.9, 7.7 Hz, 3H), 6.89
(dd, J = 7.5, 1.1 Hz, 1H), 5.26 (s, 1H), 2.58 (s, 3H), 2.39 (s, 3H), 2.04
(s, 3H); 13C NMR (126 MHz, CDCl3) δ 161.7, 145.0, 141.3, 139.1,
138.0, 134.9, 130.7, 130.6, 130.4, 129.9, 129.8, 129.5, 129.4, 129.1,
129.0, 128.9, 125.7, 67.8, 21.7, 20.0, 14.4; HRMS (ESI-TOF) m/z
calcd for C25H23NO3SNa (M + Na)+ 440.1296, found 440.1288.
4-(2-Chlorophenyl)-2-methyl-5-(phenyl(tosyl)methyl)oxazole
(23b). White solid, 40 mg, 92% yield, mp 139−140 °C; 1H NMR (500
MHz, CDCl3) δ 7.67−7.62 (m, 2H), 7.41−7.34 (m, 6H), 7.29 (td, J =
7.7, 1.7 Hz, 1H), 7.20 (td, J = 7.5, 1.3 Hz, 1H), 7.11 (d, J = 7.9 Hz,
2H), 7.03 (dd, J = 7.6, 1.6 Hz, 1H), 5.37 (s, 1H), 2.59 (s, 3H), 2.38 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 162.2, 145.0, 139.8, 138.4,
134.7, 133.1, 131.9, 131.1, 130.1, 129.9, 129.7, 129.6, 129.5, 129.4,
128.9, 128.8, 126.7, 68.50, 21.7, 14.4; HRMS (ESI-TOF) m/z calcd for
C24H20ClNO3SNa (M + Na)+ 460.0750, found 460.0750.
4-(2-Fluorophenyl)-2-methyl-5-(phenyl(tosyl)methyl)oxazole
(24b). White solid, 39 mg, 93% yield, mp 108−109 °C; 1H NMR (500
MHz, CDCl3) δ 7.69 (dd, J = 6.4, 3.1 Hz, 2H), 7.43−7.39 (m, 3H),
7.39−7.35 (m, 2H), 7.33−7.24 (m, 2H), 7.11 (td, J = 7.6, 1.1 Hz, 1H),
7.08−7.01 (m, 3H), 5.57 (d, J = 1.7 Hz, 1H), 2.58 (s, 3H), 2.34 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 162.5, 159.1 (d, J = 247.8 Hz),
145.0, 139.8, 135.1, 134.5, 131.1 (d, J = 2.9 Hz), 130.9, 130.3 (d, J =
8.4 Hz), 129.9, 129.5, 129.4, 128.9, 128.7, 124.3 (d, J = 3.4 Hz), 118.6
(d, J = 14.1 Hz), 115.9 (d, J = 22.3 Hz), 68.3 (d, J = 7.1 Hz), 21.7,
14.3; 19F NMR (377 MHz, CDCl3) δ −113.7; HRMS (ESI-TOF) m/z
calcd for C24H20FNO3SNa (M + Na)+ 444.1046, found 444.1047.
4-(Furan-2-yl)-2-methyl-5-(phenyl(tosyl)methyl)oxazole (26b).
Yellow gum, 35 mg, 89% yield; 1H NMR (500 MHz, CDCl3) δ
7.71−7.64 (m, 2H), 7.51−7.46 (m, 2H), 7.42−7.35 (m, 3H), 7.33 (dd,
J = 1.8, 0.8 Hz, 1H), 7.12 (d, J = 7.9 Hz, 2H), 6.56 (dd, J = 3.4, 0.7 Hz,
1H), 6.38 (dd, J = 3.4, 1.8 Hz, 1H), 6.07 (s, 1H), 2.54 (s, 3H), 2.32 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 162.6, 146.8, 145.0, 142.4,
137.3, 134.6, 132.3, 131.0, 130.0, 129.4, 129.3, 129.0, 128.8, 111.4,
108.6, 68.4, 21.7, 14.3; HRMS (ESI-TOF) m/z calcd for
C22H19NO4SNa (M + Na)+ 416.0932, found 416.0936.
1
Colorless gum, 41 mg, 93% yield; H NMR (500 MHz, CDCl3) δ
7.59 (dd, J = 7.6, 1.8 Hz, 2H), 7.42−7.31 (m, 10H), 7.12 (d, J = 8.1
Hz, 2H), 5.61 (s, 1H), 3.80−3.66 (m, 1H), 2.58−2.40 (m, 4H), 2.38
(s, 3H), 2.18−2.09 (m, 1H), 2.08−2.00 (m, 1H); 13C NMR (126
MHz, CDCl3) δ 167.7, 145.1, 141.0, 137.7, 134.6, 131.1, 130.8, 130.5,
129.5, 129.4, 129.1, 128.9, 128.7, 128.5, 127.8, 68.6, 33.4, 27.6, 27.5,
21.8, 18.9; HRMS (ESI-TOF) m/z calcd for C27H25NO3SNa (M +
Na)+ 466.1453, found 466.1449.
2-(Benzyloxy)-4-phenyl-5-(phenyl(tosyl)methyl)oxazole (29b).
Yellow gum, 47 mg, 95% yield; 1H NMR (400 MHz, CDCl3) δ
7.53 (dd, J = 8.1, 7.1 Hz, 4H), 7.48−7.29 (m, 13H), 7.07 (d, J = 8.0
Hz, 2H), 5.55−5.42 (m, 3H), 2.36 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 161.7, 145.0, 140.6, 134.8, 134.4, 132.9, 131.0, 130.7, 130.4,
129.5, 129.4, 129.1, 129.1, 128.8, 128.8, 128.8, 128.8, 128.7, 127.7,
73.4, 68.7, 21.8; HRMS (ESI-TOF) m/z calcd for C30H25NO4SNa (M
+ Na)+ 518.1402, found 518.1412.
2,4-Diphenyl-5-(phenyl(phenylsulfonyl)methyl)oxazole (30b).
White solid, 45 mg, 99% yield, mp 140−141 °C; 1H NMR (500
MHz, CDCl3) δ 8.16−8.08 (m, 2H), 7.65 (dd, J = 7.6, 1.9 Hz, 2H),
7.55 (ddd, J = 23.2, 6.9, 2.4 Hz, 6H), 7.48 (dd, J = 8.0, 1.6 Hz, 2H),
7.39 (dtd, J = 15.8, 8.0, 6.9 Hz, 8H), 5.72 (s, 1H); 13C NMR (126
MHz, CDCl3) δ 161.9, 142.6, 138.2, 137.5, 134.1, 131.1, 130.9, 130.7,
130.3, 129.6, 129.3, 129.0, 129.0, 128.9, 128.9, 128.9, 127.9, 127.1,
126.9, 68.7; HRMS (ESI-TOF) m/z calcd for C28H21NO3SNa (M +
Na)+ 474.1140, found 474.1142.
5-((4-Fluorophenyl)(phenylsulfonyl)methyl)-2,4-diphenyloxazole
(31b). White solid, 46 mg, 97% yield, mp 159−160 °C; 1H NMR (500
MHz, CDCl3) δ 8.12 (dd, J = 6.3, 2.3 Hz, 2H), 7.70−7.61 (m, 2H),
7.58 (d, J = 8.0 Hz, 3H), 7.55−7.49 (m, 3H), 7.48−7.32 (m, 7H), 7.09
(t, J = 8.5 Hz, 2H), 5.70 (s, 1H); 13C NMR (126 MHz, CDCl3) δ
163.6 (d, J = 249.9 Hz), 162.0, 142.7, 138.0, 137.3, 134.2, 132.6 (d, J =
8.5 Hz), 131.2, 130.7, 129.2, 129.1, 129.0, 129.0, 127.9, 126.9, 126.9,
126.1 (d, J = 3.2 Hz), 116.1 (d, J = 21.8 Hz), 116.1 (d, J = 21.8 Hz),
67.8; 19F NMR (377 MHz, CDCl3) δ −111.8; HRMS (ESI-TOF) m/z
calcd for C28H20FNO3SNa (M + Na)+ 492.1046, found 492.1042.
2,4-Diphenyl-5-(phenylsulfonyl(p-tolyl)methyl)oxazole (32b).
White solid, 38 mg, 82% yield, mp 149−150 °C; 1H NMR (500
MHz, CDCl3) δ 8.12 (dd, J = 6.6, 2.9 Hz, 2H), 7.61−7.49 (m, 8H),
7.46 (d, J = 7.4 Hz, 2H), 7.43−7.32 (m, 5H), 7.21 (d, J = 7.9 Hz, 2H),
5.69 (s, 1H), 2.37 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 161.8,
142.4, 139.8, 138.5, 137.6, 134.0, 131.0, 130.9, 130.6, 129.7, 129.3,
129.0, 128.9, 128.8, 127.9, 127.1, 127.1, 126.9, 68.4, 21.4; HRMS (ESI-
TOF) m/z calcd for C29H23NO3SNa (M + Na)+ 488.1296, found
488.1291.
5-(Methylsulfonyl(phenyl)methyl)-2,4-diphenyloxazole (33b).
White solid, 36 mg, 93% yield, mp 167−169 °C; 1H NMR (500
MHz, CDCl3) δ 8.20−8.13 (m, 2H), 7.77 (dd, J = 7.8, 1.7 Hz, 2H),
7.73−7.67 (m, 2H), 7.55−7.40 (m, 9H), 5.68 (s, 1H), 2.85 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 162.2, 142.6, 138.0, 131.2, 130.9,
130.8, 130.2, 129.9, 129.5, 129.2, 129.1, 129.1, 128.1, 127.0, 126.9,
67.5, 39.2; HRMS (ESI-TOF) m/z calcd for C23H19NO3SNa (M +
Na)+ 412.0983, found 412.0994.
5-(Methylsulfonyl(p-tolyl)methyl)-2,4-diphenyloxazole (34b).
White solid, 33 mg, 83% yield, mp 166−167 °C; 1H NMR (500
MHz, CDCl3) δ 8.21−8.09 (m, 2H), 7.73−7.68 (m, 2H), 7.65 (d, J =
8.1 Hz, 2H), 7.47 (ddd, J = 28.8, 10.0, 5.2 Hz, 6H), 7.28 (d, J = 7.9 Hz,
2H), 5.65 (s, 1H), 2.84 (s, 3H), 2.38 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 162.1, 142.3, 140.0, 138.2, 131.1, 130.9, 130.2, 130.0, 129.2,
129.1, 128.0, 127.7, 127.1, 126.9, 67.2, 39.1, 21.4; HRMS (ESI-TOF)
m/z calcd for C24H21NO3SNa (M + Na)+ 426.1140, found 426.1144.
5-((4-Fluorophenyl)(methylsulfonyl)methyl)-2,4-diphenyloxazole
(35b). White solid, 34 mg, 83% yield, mp 191−193 °C; 1H NMR (500
MHz, CDCl3) δ 8.20−8.11 (m, 2H), 7.81−7.74 (m, 2H), 7.72−7.66
2-Cyclopropyl-4-phenyl-5-(phenyl(tosyl)methyl)oxazole (27b).
1
Colorless gum, 37 mg, 86% yield; H NMR (500 MHz, CDCl3) δ
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Article
(m, 2H), 7.56−7.47 (m, 5H), 7.45 (d, J = 7.3 Hz, 1H), 7.18 (t, J = 8.6
Hz, 2H), 5.67 (s, 1H), 2.84 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
163.7 (d, J = 250.5 Hz), 162.3, 142.6, 137.8, 132.2 (d, J = 8.5 Hz),
131.3, 130.8, 129.3, 129.2, 129.1, 128.0, 126.9, 126.4 (d, J = 3.2 Hz),
116.6 (d, J = 21.8 Hz), 66.5, 39.2; 19F NMR (471 MHz, CDCl3) δ
−110.9; HRMS (ESI-TOF) m/z calcd for C23H18FNO3SNa (M +
Na)+ 430.0889, found 430.0879.
2-Methyl-5-(methylsulfonyl(phenyl)methyl)-4-phenyloxazole
(36b). White solid, 26 mg, 81% yield, mp 168−169 °C; 1H NMR (500
MHz, CDCl3) δ 7.74−7.67 (m, 2H), 7.63−7.57 (m, 2H), 7.50−7.43
(m, 5H), 7.40 (ddd, J = 7.4, 3.7, 1.3 Hz, 1H), 5.59 (s, 1H), 2.79 (s,
3H), 2.61 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 162.3, 141.3,
137.7, 130.9, 130.9, 130.1, 129.8, 129.4, 129.1, 129.0, 127.9, 67.3, 39.1,
14.4; HRMS (ESI-TOF) m/z calcd for C18H17NO3SNa (M + Na)+
350.0827, found 350.0837.
under Ar. The resulting mixture was allowed to stand while its
temperature increased from −78 to −40 °C for about 1 h until the N-
tosylaldimines had disappeared. 2-Methoxyacetyl chloride was added
in one portion below −40 °C and allowed to stand for 5 min. The
mixture was immediately warmed to rt and allowed to stand for 30
min, followed by quenching with water. The separated organic layer
was washed with brine and dried over MgSO4. After removal of the
solvent, the residue was purified by flash column chromatography to
give the desired product 38c. Colorless crystals, 1.4 g, 65% yield, mp
175−176 °C; 1H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 8.1 Hz, 2H),
7.52 (d, J = 7.4 Hz, 4H), 7.45−7.31 (m, 6H), 7.16 (d, J = 6.9 Hz, 2H),
6.95 (s, 1H), 4.20 (d, J = 16.3 Hz, 1H), 4.04 (s, 1H), 3.33 (s, 3H), 2.37
(s, 3H); 13C NMR (126 MHz, CDCl3) δ 208.1, 169.0, 145.3, 135.8,
132.9, 131.1, 129.5, 129.4, 129.3, 129.3, 129.3, 129.0, 128.4, 125.4,
111.4, 103.6, 71.0, 59.5, 21.7; HRMS (ESI-TOF) m/z calcd for
C25H23NO4SNa (M + Na)+ 456.1245, found 456.1243.
5-((4-Fluorophenyl)(methylsulfonyl)methyl)-2-methyl-4-phenyl-
1
oxazole (37b). White solid, 30 mg, 87% yield, mp 177−178 °C; H
2-(Methoxymethyl)-4-phenyl-5-(phenyl(tosyl)methyl)oxazole
(38b). A 10 mL vial equipped with a magnetic stirrer was charged with
38c (0.1 mmol), DBU (2 mg, 10 mol %), and CH3CN (1 mL). The
mixture was stirred at ambient temperature for 4 h under air. The
crude mixture was then concentrated and purified by flash column
chromatography to give the desired product 38b. Colorless gum, 42
NMR (500 MHz, CDCl3) δ 7.74−7.65 (m, 2H), 7.62−7.56 (m, 2H),
7.48−7.43 (m, 2H), 7.43−7.37 (m, 1H), 7.15 (t, J = 8.6 Hz, 2H), 5.58
(s, 1H), 2.78 (s, 3H), 2.61 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
163.6 (d, J = 250.4 Hz), 162.4, 141.3, 137.5, 132.1 (d, J = 8.4 Hz),
130.8, 129.2, 129.1, 127.8, 126.6 (d, J = 3.4 Hz), 116.5 (d, J = 21.8
Hz), 66.4, 39.1, 14.4; 19F NMR (471 MHz, CDCl3) δ −111.0; HRMS
(ESI-TOF) m/z calcd for C18H16FNO3SNa (M + Na)+ 368.0733,
found 368.0740.
1
mg, 96% yield; H NMR (500 MHz, CDCl3) δ 7.58 (dd, J = 7.9, 1.6
Hz, 2H), 7.43−7.32 (m, 10H), 7.12 (d, J = 8.0 Hz, 2H), 5.63 (s, 1H),
4.62 (s, 2H), 3.52 (s, 3H), 2.37 (s, 3H); 13C NMR (126 MHz, CDCl3)
δ 161.3, 145.2, 141.2, 139.2, 134.4, 130.7, 130.6, 130.2, 129.5, 129.5,
129.1, 129.0, 128.8, 127.8, 68.5, 66.5, 59.2, 21.8; HRMS (ESI-TOF)
m/z calcd for C25H24NO4S (M + H)+ 434.1426, found 434.1425.
N-(1,3-Diphenylprop-2-ynyl)benzamide (1e). 1e was prepared
according to the literature procedure.13 1H NMR (500 MHz,
CDCl3) δ 7.82 (dd, J = 5.2, 3.3 Hz, 2H), 7.66 (d, J = 7.2 Hz, 2H),
7.55−7.46 (m, 3H), 7.46−7.37 (m, 4H), 7.37−7.29 (m, 4H), 6.77 (d, J
= 8.4 Hz, 1H), 6.50 (d, J = 8.5 Hz, 1H); 13C NMR (126 MHz, CDCl3)
δ 166.3, 139.2, 134.0, 132.0, 131.9, 128.9, 128.7, 128.4, 128.3, 127.3,
127.3, 122.6, 87.1, 85.2, 45.8.
General Procedure for the Synthesis of Allenylamides c
from a. A 10 mL vial equipped with a magnetic stirrer was charged
with N-sulfonyl propargylamide a (0.1 mmol), DABCO (1 mg, 10 mol
%), and DCM (2 mL). The mixture was stirred at rt for 30 min under
air. The crude mixture was then concentrated and purified by flash
column chromatography to give the desired product c. (1c, 18c, 19c,
and 36c were all prepared by this procedure.)
N-(1,3-Diphenylpropa-1,2-dienyl)-N-tosylbenzamide (1c). White
solid, 45 mg, 98% yield, mp 189−190 °C; 1H NMR (500 MHz,
CDCl3) δ 8.05−7.98 (m, 2H), 7.61−7.56 (m, 2H), 7.47−7.43 (m,
2H), 7.43−7.36 (m, 3H), 7.32 (d, J = 7.3 Hz, 1H), 7.25−7.16 (m,
7H), 6.93 (d, J = 7.2 Hz, 2H), 6.56 (s, 1H), 2.40 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 209.2, 170.3, 145.1, 135.8, 134.4, 134.3, 131.7,
131.3, 129.9, 129.3, 129.0, 129.0, 128.8, 128.5, 128.3, 128.2, 128.0,
126.0, 114.7, 103.3, 21.8; HRMS (ESI-TOF) m/z calcd for
C29H23NO3SNa (M + Na)+ 488.1296, found 488.1309.
N-(1,3-Diphenylpropa-1,2-dienyl)-N-tosylacetamide (18c). White
solid, 39 mg, 97% yield, mp 53−57 °C; 1H NMR (500 MHz, CDCl3)
δ 7.88 (d, J = 4.4 Hz, 2H), 7.68−7.39 (m, 8H), 7.35 (dd, J = 15.6, 7.8
Hz, 2H), 7.17 (s, 2H), 6.98 (s, 1H), 2.37 (s, 3H), 2.17 (s, 3H); 13C
NMR (126 MHz, CDCl3) δ 208.1, 170.1, 145.0, 136.2, 133.3, 131.3,
129.3, 129.3, 129.2, 129.1, 128.8, 128.3, 125.5, 113.6, 103.4, 24.1, 21.7;
HRMS (ESI-TOF) m/z calcd for C24H21NO3SNa (M + Na)+
426.1140, found 426.1132.
5-Benzyl-2,4-diphenyloxazole (1f). A 10 mL vial equipped with a
magnetic stirrer was charged with 1e (31 mg, 0.1 mmol), DBU (15
mg, 0.1 mmol), and CH3CN (1 mL). The mixture was stirred at
ambient temperature for 2 h under air. The crude mixture was then
concentrated and purified by flash column chromatography to give the
1
desired product 1f. Colorless gum, 29 mg, 94% yield; H NMR (500
MHz, CDCl3) δ 8.08−8.01 (m, 2H), 7.75−7.70 (m, 2H), 7.44−7.36
(m, 5H), 7.33−7.24 (m, 5H), 7.24−7.18 (m, 1H), 4.28 (s, 2H); 13C
NMR (126 MHz, CDCl3) δ 160.3, 145.8, 137.4, 137.4, 132.3, 130.3,
128.9, 128.8, 128.4, 127.8, 127.7, 127.2, 126.9, 126.5, 32.1. Data are in
accordance with the previously reported results.5b
N-(3-Cyclohexyl-1-phenylpropa-1,2-dienyl)-N-tosylacetamide
ASSOCIATED CONTENT
■
(19c). Stop the reaction after 24 h to produce colorless gum, 38 mg,
1
S
* Supporting Information
92% yield; H NMR (500 MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 2H),
1H and 13C NMR spectra of all compounds and crystallographic
data (CIF) of 1a and 38c. This material is available free of
charge via the Internet at http://pubs.acs.org.
7.43 (d, J = 7.6 Hz, 2H), 7.36 (t, J = 7.8 Hz, 2H), 7.28 (t, J = 7.5 Hz,
3H), 5.83 (d, J = 91.9 Hz, 1H), 2.43 (s, 3H), 2.35 (t, J = 16.6 Hz, 1H),
2.07 (s, 3H), 1.89−1.66 (m, 4H), 1.42−1.09 (m, 6H); 13C NMR (126
MHz, CDCl3) δ 204.0, 170.5, 144.9, 136.4, 134.2, 129.4, 129.2, 129.0,
128.1, 125.1, 110.7, 106.5, 38.6, 33.2, 33.1, 25.9, 24.1, 21.8; HRMS
(ESI-TOF) m/z calcd for C24H27NO3SNa (M + Na)+ 432.1604, found
431.9787.
AUTHOR INFORMATION
■
Corresponding Author
*B.W.: bswan@dicp.ac.cn. X.L.: xwli@dicp.ac.cn.
N-(1,3-Diphenylpropa-1,2-dienyl)-N-(methylsulfonyl)acetamide
1
(36c). White solid, 31 mg, 96% yield, mp 57−59 °C; H NMR (400
MHz, CDCl3) δ 7.50 (dd, J = 15.3, 7.9 Hz, 4H), 7.42−7.35 (m, 4H),
7.35−7.28 (m, 2H), 6.98 (s, 1H), 3.34 (s, 3H), 2.27 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 207.4, 171.5, 132.9, 131.0, 129.3, 129.2, 129.1,
128.8, 128.2, 125.3, 113.0, 103.5, 41.9, 24.0; HRMS (ESI-TOF) m/z
calcd for C18H17NO3SNa (M + Na)+ 350.0827, found 350.0837.
N-(1,3-Diphenylpropa-1,2-dienyl)-2-methoxy-N-tosylacetamide
(38c). To a solution of N-tosylaldimines (1.3 g, 5 mmol) and
phenylacetylene (562 mg, 5.5 mmol) in 20 mL of dry CH2Cl2, was
added dropwise LHMDS in THF (1 M, 5 mL, 5 mmol) at −78 °C
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the financial support from the National
Basic Research Program of China (2010CB833300) and the
National Natural Science Foundation of China (21172218).
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Article
(12) The N-sulfonylaldimines were prepared following the procedure
described in the literature: Love, B. E.; Raje, P. S.; Williams, T. C., II.
Synlett 1994, 493.
(13) Zhan, Z.; Yang, W.; Yang, R.; Yu, J.; Li, J.; Liu, H. Chem.
Commun. 2006, 3352.
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Yamagishi, U.; Song, D.; Konta, S.; Yamamoto, Y. Angew. Chem., Int.
Ed. 2007, 46, 2284. (c) Yeom, H.-S.; So, E.; Shin, S. Chem.Eur. J.
2011, 17, 1764.
(8) Xin, X.; Wang, D.; Li, X.; Wan, B. Angew. Chem., Int. Ed. 2012, 51,
1693.
(9) The identities of 1b and 38c were confirmed by X-ray
crystallography. See CCDC 925075 (1b) and CCDC 928506 (38c)
for the crystallographic data.
(10) For zwitterionic intermediates, see: (a) Xia, Y.; Dudnik, A. S.; Li,
Y.; Gevorgyan, V. Org. Lett. 2010, 12, 5538. (b) Seregin, I. V.;
Gevorgyan, V. J. Am. Chem. Soc. 2006, 128, 12050.
(11) One reviewer of this work presumed that the 1d was
desulfonated 1a (1e). To verify, we prepared 1e according the
literature procedure (ref 13). 1e did cyclize to the oxazle 1f under the
DBU/CH3CN condition. But when we checked using HPLC, we
found neither 1e (3.6 min) nor 1f (16.2 min) was 1d (7.1 min). In
addition, during the whole course of cyclization of 1a, we did not find
any trace of 1e or 1f during HPLC. Therefore, 1d is certainly not
desulfonated 1a.
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