Tf2NH-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with Dioxazoles: A Metal-Free Approach to Polysubstituted 4-Aminooxazoles

Article abstract of DOI:10.1021/acs.joc.7b00076

An unprecedented Tf₂NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.

Full text of DOI:10.1021/acs.joc.7b00076

Note
pubs.acs.org/joc
Tf2NH-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with
Dioxazoles: A Metal-Free Approach to Polysubstituted
4‑Aminooxazoles
Yingying Zhao,†,‡,§ Yancheng Hu,†,§ Chunxiang Wang,† Xincheng Li,*,† and Boshun Wan*,†
†Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China
‡University of Chinese Academy of Sciences, Beijing 10049, China
S
* Supporting Information
ABSTRACT: An unprecedented Tf2NH-catalyzed formal [3 + 2]
cycloaddition of ynamides with dioxazoles was developed to construct
various polysubstituted 4-aminooxazoles. This approach features a
metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost
catalyst, exceptionally mild reaction conditions, a very short reaction
time, a broad substrate scope, and high efficiency. This metal-free
protocol may find applications in pharmaceutical-oriented synthesis.
Scheme 1. Gold- versus Acid-Catalyzed Cycloadditions of
Ynamides with Dioxazoles
xazoles are important structural motifs in a broad range
Oof natural products, bioactive molecules, and pharma-
ceutical ingredients.1 Consequently, their synthesis has
attracted considerable attention over the past decade. Among
those synthetic routes,2,3 the bimolecular cycloaddition
approach, due to its formation of multiple new bonds in one
step, is arguably the simplest and most straightforward.3,7
However, most of them rely on transition-metal catalysis. By
contrast, the metal-free catalytic cycloadditions are extremely
rare.9 The metal-free protocol avoids the utilization of
transition metal catalysts, thus resulting in no metal residues
in the system, which is highly advantageous in the
pharmaceutical-oriented synthesis.4 In this context, the
exploration of metal-free catalytic bimolecular assembly of
oxazoles is in high demand.
In recent years, ynamides have emerged as versatile building
blocks to elaborate complex heterocyclic scaffolds due to their
specific reactivity.5 For example, gold-catalyzed cycloadditions
of ynamides with various unsaturated precursors have been
extensively investigated.6,7 In these reactions, α-imino gold
carbene was suggested to be the key intermediate. Following
the same principle, very recently, Liu et al. presented a gold-
catalyzed cycloaddition of ynamides with dioxazoles for the
synthesis of functionalized oxazoles (Scheme 1a).7 Besides gold
catalysis, ynamides could also be activated by acid catalysts to
form keteniminium ion intermediates, which then easily
underwent the reactions with nucleophiles.8 This strategy has
been employed to construct pyridines, pyrimidines, and
isoquinolines.9 Inspired by these elegant works and our long-
standing interests in exploring new methodologies toward
oxazoles,10 we envisioned that if ynamides would be first
activated by Brønsted acids such as Tf2NH and TfOH,8,9 then
the in situ generated keteniminium ion intermediates undergo
the cycloadditions with dioxazoles to give 4-aminooxazoles
(Scheme 1b). Indeed, the reaction proceeded efficiently in the
presence of Tf2NH at room temperature within a very short
reaction time (5 min). Remarkably, the IPrAuNTf2 catalyst
used in Liu’s work is nearly 44 times more expensive than
Tf2NH and 1390 times more expensive than TfOH,11 making
Received: January 11, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.7b00076
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
the metal-free approach a highly economical alternative to a
noble metal catalyst. Thus, our approach features the first
metal-free acid-catalyzed [3 + 2] cycloaddition toward oxazoles,
a low-cost catalyst, exceptionally mild reaction conditions, and a
very short reaction time. These amazing advantages will
certainly enable this metal-free catalytic protocol to find
applications in organic synthesis, especially in the synthesis of
pharmaceuticals. Herein, we report the results of our studies.
We initiated our investigation by reacting ynamide 1a and
dioxazole 2a in the presence of Tf2NH (1.2 equiv). As
expected, the cycloaddition proceeded efficiently under this
condition, providing the desired product 3aa in 82% yield
(Table 1, entry 1). Notably, the reaction can be finished within
With the optimal reaction conditions in hand, we first
explored the scope of ynamides and the results are summarized
in Scheme 2. The variations of R1 group at the terminal alkyne
a
Scheme 2. Scope of Substrates
a
Table 1. Optimization of the Reaction Conditions
b
entry
acid
x
dioxazole
solvent
yield (%)
1
2
3
4
5
Tf2NH
Tf2NH
Tf2NH
Tf2NH
Tf2NH
Tf2NH
TfOH
1.2
2a
2a′
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
THF
DCE
82
28
81
82
77
86
83
0
1.2
0.1
0.05
0.025
0.05
0.05
0.05
0.05
0.05
0.05
0.05
c
6
c
7
c
8
c
CF3CO2H
TsOH
9
0
c
10
Tf2NH
Tf2NH
Tf2NH
70
0
c
11
cd
,
12
77
a
Reaction conditions: Tf2NH (5 mol %) was added to a mixture of
a
Reaction conditions: Acid was added to a mixture of 1a (0.1 mmol)
ynamide 1 (0.2 mmol) and dioxazole 2 (0.24 mmol) in DCE (2.0 mL)
b
and 2a (0.2 mmol) in DCE (1.0 mL) and then stirred at room
temperature for 5 min. Yields were determined by HPLC using
naphthalene as the internal standard. 0.12 mmol of 2a was used. The
reaction was conducted under open-air conditions.
and then stirred at room temperature for 5 min. 1.0 equiv of Tf2NH
b
c
was employed. 12 h. Ts = p-toluenesulfonyl, Ms = methanesulfonyl,
c
d
p-Ns = p-nitrobenzenesulfonyl.
were first examined. A series of substituents at the ortho-, meta-,
and para-positions of the phenyl ring were all well tolerated,
providing the corresponding 4-aminooxazoles 3ba−3ja in good
to excellent yields. The electronic properties and positions of
the substituents have a neglectable effect on the reactivity.
Notably, treatment of 2-thienyl derived ynamide 1k with a
catalytic amount of Tf2NH afforded the desired product 3ka in
95% yield. Surprisingly, desilylated oxazole 3la was found to be
the main product when using TIPS-substituted ynamide 1l as
the substrate. Consequently, in this case, 1 equiv of Tf2NH was
required to achieve a moderate yield. Furthermore, other alkyl
groups such as n-butyl and cyclohexyl in R1 were also
compatible with the process, producing 4-aminooxazoles 3ma
and 3na in acceptable yields albeit with a longer reaction time.
The effects of the electron-withdrawing groups on the nitrogen
atom were next investigated. The reactions of ynamides bearing
N-Ms, N-SO2Ph, and N-Ns with 2a furnished the correspond-
ing products 3oa−3qa in 78−89% yields. However, when the
sterically hindered 2-naphthyl substituent was employed in the
sulfonyl group, 4-aminooxazole 3ra was only afforded in 69%
yield. The more electron-rich ynamide 1s possessing an
oxazolidine group can also participate in the reaction, giving
3sa in a moderate yield after prolonging the reaction time to 12
5 min. However, the utilization of dioxazole 2a′ as the
cycloaddition partner only afforded 3aa in 28% yield (entry 2).
The catalyst loading was then investigated, and a catalytic
amount of Tf2NH was used to promote the reaction. We were
delighted to find that 10 mol % of Tf2NH could efficiently
catalyze the cycloaddition, producing 3aa in a comparable yield
(entry 3). A lower catalyst loading (5 mol %) also gave a good
result, while 77% yield of 3aa was achieved in the presence of
2.5 mol % of catalyst (entries 4 and 5). Pleasingly, when the
amount of dioxazole 2a was decreased to 1.2 equiv, the yield of
3aa increased to 86% (entry 6). It is noteworthy that the use of
TfOH as catalyst also delivered the desired oxazole 3aa in a
comparable yield (entry 7).12 The other Brønsted acids such as
CF3CO2H and TsOH cannot promote the reaction (entries 8
and 9). When the solvent was changed to DCM, the reaction
also occurred but gave an inferior result (entry 10). By contrast,
no desired product was obtained when the reaction was
performed in THF (entry 11). Disappointedly, when the
reaction was conducted under open-air conditions, a moderate
yield was obtained (entry 12). It is because the side product
amide was easily formed by the acid-catalyzed addition of water
with ynamide.8a
B
DOI: 10.1021/acs.joc.7b00076
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The Journal of Organic Chemistry
Note
h. The substituted benzyl group such as 4-BrC6H4CH2 on the
nitrogen atom was compatible with this process (3ta). Notably,
when R2 was changed to the phenyl group, the cycloaddition
also proceeded with high efficiency (3ua, 97%). In the cases of
N-methyl and N-allyl ynamides 1v and 1w, the reactions
afforded the corresponding oxazoles in 75% and 70% yield,
respectively.
dioxazole 2a to afford the intermediate B. A subsequent ring
fragmentation of B occurs, leading to the formation of benzylic
carbocation C with the elimination of acetone. The nucleophilic
attack of the carbonyl oxygen atom onto the carbocation
produces intermediate D. Finally, deprotonation of D delivers
the desired product 3aa and regenerates the acid catalyst.
In summary, we describe herein an unprecedented Tf2NH-
catalyzed formal [3 + 2] cycloaddition of ynamides with
dioxazoles for the construction of various polysubstituted 4-
aminooxazoles. This approach features a metal-free catalytic
bimolecular assembly of oxazole motifs, a low-cost catalyst,
exceptionally mild reaction conditions, a very short reaction
time, a broad substrate scope, and high efficiency. We believe
that this work will pave a new way for the exploration of acid-
catalyzed cycloadditions of ynamides with other unsaturated
precursors.
Subsequently, a wide range of substituted dioxazoles were
surveyed. Dioxazole 2b with an electron-donating group 2-
OMe on the phenyl ring underwent the reaction efficiently,
generating product 3ab in 89% yield. A variety of meta- and
para-substituted groups, such as Cl, F, Me, OMe, and CF3,
were all suitable for this process, leading to the formation of
highly functionalized 4-aminooxazoles 3ac−3ah in good to
excellent yields. These results reveal that the steric and
electronic factors had little influence on the reaction course.
The cycloaddition of 2-furyl substituted dioxazole 2i with
ynamide 1a produced the desired oxazole 3ai in 91% yield.
Besides, when an alkyl substituent such as cyclohexyl was
employed in R (2j), the reaction also occurred under the
standard conditions albeit with a slightly decreased yield.
To illustrate the practical application of this method, a gram-
scale experiment was conducted. Ynamide 1a (2.7 mmol) and
dioxazole 2a (3.2 mmol) were dissolved in 30 mL of DCE.
Then a catalytic amount of Tf2NH (5 mol %) was added, and
the mixture was stirred at room temperature for 5 min. The
reaction was quenched by Et3N, and removal of the solvent and
direct crystallization in DCM/petroleum ether afforded 3aa in
84% yield (1.09 g). Alternatively, a comparable yield could also
be obtained by using a much cheaper TfOH catalyst albeit with
a slightly longer reaction time (20 min). To further
demonstrate the advantage of our protocol, we also conducted
the reaction using a gold catalyst (5 mol % of IPrAuNTf2, Liu’s
work). It is noted that a much longer reaction time (6 h versus
5 min) was required to achieve a comparable yield (1.06 g,
81%). Thus, our metal-free catalytic reaction provides an
economical alternative for the synthesis of aminooxazoles.
According to the precedents on the chemistry of the
keteniminium ion,8,9 a plausible mechanism was proposed in
Scheme 3. Initially, in the presence of Tf2NH, ynamide 1a
proceeds through a protonation step to form keteniminium ion
intermediate A. Then, A is attacked by the nitrogen atom of
EXPERIMENTAL SECTION
■
General Information. Unless otherwise noted, all manipulations
and reactions were conducted under an inert atmosphere using
standard Schlenk techniques or in an argon-filled glovebox. All
chemicals were purchased from commercial sources and were used
without further purification. Solvents were treated prior to use
according to the standard methods. Column chromatography was
carried out on silica gel (300−400 mesh) using a forced flow of eluent
at 0.3−0.5 bar pressure. NMR spectra were recorded at room
temperature in CDCl3 on 400 MHz spectrometers. The chemical shifts
1
for H NMR were recorded in ppm downfield from tetramethylsilane
(TMS) with CDCl3 (7.26 ppm) as the internal standard. The chemical
shifts for 13C NMR were recorded in ppm downfield using the central
peak of CDCl3 (77.16 ppm) as the internal standard. Coupling
constants (J) are reported in hertz and refer to apparent peak
multiplications. The abbreviations s, d, t, q, and m stand for singlet,
doublet, triplet, quartet, and multiplet in that order. HRMS data were
obtained with a Micromass HPLC-Q-TOF mass spectrometer (ESI).
General Procedure for the Synthesis of Ynamides. N-Alkyl
substituted ynamides 1a−1t, 1v, and 1w were synthesized by copper-
catalyzed cross-couplings of amides with the corresponding alkynyl
bromides.7,13 N-Phenyl substituted ynamide 1u was synthesized by
iron-catalyzed cross-coupling of phenylbenzenesulfonamide with
(bromoethynyl)benzene.7
General Procedure 1 (GP 1). In a 50 mL flame-dried Schlenk tube,
N-alkyl substituted amides (5.0 mmol), CuSO4·5H2O (10 mol %,
125.0 mg), 1,10-phenanthroline (20 mol %, 180.0 mg), K2CO3 (2.0
equiv, 1.38 g), and toluene (20 mL) were added in sequence under an
argon atmosphere. Then alkynyl bromides (6.0 mmol) were
introduced, and the resulting mixture was stirred at 80 °C for 12 h.
Afterward, the crude mixture was filtered through a short pad of Celite
and washed with ethyl acetate. Removal of the solvent and purification
by silica gel column chromatography yielded the N-alkyl substituted
ynamides (eluent: petroleum ether/ethyl acetate 10/1).
Scheme 3. Proposed Mechanism
General Procedure 2 (GP 2). In a 50 mL flame-dried Schlenk tube,
4-methyl-N-phenylbenzenesulfonamide (5.0 mmol, 1.24 g), FeCl3·
6H2O (10 mol %, 135.2 mg), K2CO3 (2.0 equiv, 1.38 g), and toluene
(20 mL) were added in sequence under an argon atmosphere. Then
N,N′-dimethyl-1,2-ethanediamine (DMEDA, 20 mol %, 108 μL) and
(bromoethynyl)benzene (6.0 mmol, 1.09 g) were introduced. The
resulting mixture was stirred at 90 °C for 12 h. Afterward, the crude
mixture was filtered through a short pad of Celite and washed with
ethyl acetate. Removal of the solvent and purification by silica gel
column chromatography yielded the N-phenyl ynamide 1u (eluent:
petroleum ether/ethyl acetate 10/1).
N-Benzyl-4-methyl-N-(phenylethynyl)benzenesulfonamide (1a).
Known compound;13 7.8 g (in 25 mmol scale); 96% yield; 1H
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.2 Hz, 2H), 7.36−7.28 (m,
7H), 7.26−7.19 (m, 5H), 4.58 (s, 2H), 2.44 (s, 3H).
N-Benzyl-4-methyl-N-(o-tolylethynyl)benzenesulfonamide (1b).
Known compound;8a 790.0 mg (in 3.0 mmol scale); 70% yield; H
1
C
DOI: 10.1021/acs.joc.7b00076
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The Journal of Organic Chemistry
Note
NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.1 Hz, 2H), 7.38−7.26 (m,
7H), 7.18 (d, J = 7.5 Hz, 1H), 7.14−7.02 (m, 3H), 4.59 (s, 2H), 2.42
(s, 3H), 2.16 (s, 3H).
N-Benzyl-N-((2-methoxyphenyl)ethynyl)-4-methylbenzenesulfon-
amide (1c). Known compound;13 843.5 mg (in 3.0 mmol scale); 72%
yield; 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2H), 7.40−
7.34 (m, 2H), 7.33−7.24 (m, 5H), 7.23−7.16 (m, 2H), 6.88−6.73 (m,
2H), 4.59 (s, 2H), 3.81 (s, 3H), 2.42 (s, 3H).
8.0 Hz, 2H), 7.36−7.24 (m, 5H), 4.43 (s, 2H), 2.46−2.30 (m, 4H),
1.63−1.46 (m, 4H), 1.42−1.32 (m, 1H), 1.31−1.17 (m, 5H).
N-Benzyl-N-(phenylethynyl)methanesulfonamide (1o). Known
compound;7 785.6 mg (in 4.0 mmol scale); 69% yield; 1H NMR
(400 MHz, CDCl3) δ 7.51−7.46 (m, 2H), 7.43−7.32 (m, 5H), 7.31−
7.25 (m, 3H), 4.71 (s, 2H), 2.93 (s, 3H).
N-Benzyl-N-(phenylethynyl)benzenesulfonamide (1p). Known
compound;13 500.0 mg (in 5.0 mmol scale); 29% yield; H NMR
1
N-Benzyl-N-((2-fluorophenyl)ethynyl)-4-methylbenzenesulfon-
(400 MHz, CDCl3) δ 7.91 (d, J = 7.7 Hz, 2H), 7.63 (t, J = 7.4 Hz,
1H), 7.52 (t, J = 7.7 Hz, 2H), 7.35−7.28 (m, 5H), 7.27−7.20 (m, 5H),
4.61 (s, 2H).
amide (1d). White solid; 1.12 g (in 3.4 mmol scale); 87% yield; mp
1
72−73 °C; H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.2 Hz, 2H),
7.37−7.27 (m, 7H), 7.26−7.17 (m, 2H), 7.05−6.96 (m, 2H), 4.59 (s,
2H), 2.43 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 162.4 (d, J =
250.6 Hz), 144.8, 134.7, 134.4, 133.0 (d, J = 1.4 Hz), 129.8, 1129.3 (d,
J = 7.8 Hz), 129.1, 128.6, 128.5, 127.9, 123.9 (d, J = 3.7 Hz), 115.4 (d,
J = 20.7 Hz), 111.6 (d, J = 15.7 Hz), 87.5, 65.3, 55.9, 21.8. 19F NMR
(376 MHz, CDCl3) δ −110.27. HRMS (ESI) calcd for C22H19FNO2S
[M + H]+ 380.1115, found 380.1121.
N-Benzyl-4-nitro-N-(phenylethynyl)benzenesulfonamide (1q).
Known compound;13 574.0 mg (in 2.5 mmol scale); 58% yield; H
1
NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.6 Hz, 2H), 7.98 (d, J = 8.5
Hz, 2H), 7.39−7.22 (m, 10H), 4.68 (s, 2H).
N-Benzyl-N-(phenylethynyl)naphthalene-2-sulfonamide (1r). Yel-
low solid; 570.0 mg (in 2.5 mmol scale); 80% yield; mp 109−110 °C;
1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.97−7.86 (m, 4H),
N-Benzyl-N-((2-bromophenyl)ethynyl)-4-methylbenzenesulfon-
amide (1e). Known compound;18 0.9 g (in 2.5 mmol scale); 82%
7.68−7.57 (m, 2H), 7.36−7.30 (m, 2H), 7.28−7.19 (m, 8H), 4.64 (s,
2H). 13C {1H} NMR (100 MHz, CDCl3) δ 135.3, 134.6, 134.4, 132.1,
131.3, 129.5, 129.4, 129.0, 128.6, 128.5, 128.3, 128.1, 127.9, 127.78,
122.77, 122.7, 82.7, 71.5, 56.0. HRMS (ESI) calcd for C25H20NO2S
[M + H]+ 398.1209, found 398.1215.
1
yield; H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.1 Hz, 2H), 7.49
(d, J = 7.8 Hz, 1H), 7.40−7.34 (m, 2H), 7.34−7.27 (m, 5H), 7.24−
7.14 (m, 2H), 7.10−7.03 (m, 1H), 4.62 (s, 2H), 2.43 (s, 3H).
N-Benzyl-N-((3-fluorophenyl)ethynyl)-4-methylbenzenesulfon-
amide (1f). Yellow solid; 0.98 g (in 3.0 mmol scale); 86% yield; mp
3-(Phenylethynyl)oxazolidin-2-one (1s). Known compound;7
200.0 mg (in 2.5 mmol scale); 43% yield; 1H NMR (400 MHz,
CDCl3) δ 7.48−7.40 (m, 2H), 7.35−7.27 (m, 3H), 4.53−4.43 (m,
2H), 4.04−3.95 (m, 2H).
1
69−70 °C; H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.3 Hz, 2H),
7.37−7.29 (m, 7H), 7.23−7.16 (m, 1H), 7.01−6.86 (m, 3H), 4.58 (s,
2H), 2.45 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 162.4 (d, J =
246.2 Hz), 145.0, 134.7, 134.3, 129.93, 129.9 (d, J = 9.2 Hz), 129.0,
128.7 128.6, 127.8, 126.9 (d, J = 3.1 Hz), 124.8 (d, J = 9.6 Hz), 117.8
(d, J = 22.8 Hz), 115.0 (d, J = 21.2 Hz), 83.7, 70.7 (d, J = 3.5 Hz),
55.7, 21.8. 19F NMR (376 MHz, CDCl3) δ −113.16. HRMS (ESI)
calcd for C22H19FNO2S [M + H]+ 380.1115, found 380.1119.
N-Benzyl-4-methyl-N-(p-tolylethynyl)benzenesulfonamide (1g).
N-(4-Bromobenzyl)-4-methyl-N-(phenylethynyl)benzenesulfon-
amide (1t). Yellow solid; 790.0 mg (in 2.5 mmol scale); 72% yield; mp
1
65−66 °C; H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.1 Hz, 2H),
7.42 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.27−7.16 (m, 6H),
4.52 (s, 2H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 144.9,
134.7, 133.7, 131.8, 131.3, 130.6, 129.9, 128.4, 128.0, 127.8, 122.7,
122.6, 82.5, 71.6, 55.2, 21.8. HRMS (ESI) calcd for C22H19BrNO2S [M
+ H]+ 440.0314, found 440.0313.
Known compound;16 680 mg (in 2.5 mmol scale); 73% yield; H
1
NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.1 Hz, 2H), 7.39−7.25 (m,
7H), 7.13 (d, J = 7.9 Hz, 2H), 7.04 (d, J = 7.9 Hz, 2H), 4.56 (s, 2H),
2.43 (s, 3H), 2.30 (s, 3H).
N-Benzyl-N-((4-methoxyphenyl)ethynyl)-4-methylbenzenesulfon-
amide (1h). Known compound;16 341.0 mg (in 3.0 mmol scale); 29%
yield; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.3 Hz, 2H), 7.36−
7.26 (m, 7H), 7.19 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 4.56
(s, 2H), 3.77 (s, 3H), 2.44 (s, 3H).
N-Benzyl-N-((4-fluorophenyl)ethynyl)-4-methylbenzenesulfon-
amide (1i). Known compound;18 510.0 mg (in 2.5 mmol scale); 54%
yield; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 2H), 7.37−
7.27 (m, 7H), 7.19 (dd, J = 8.5, 5.4 Hz, 2H), 6.92 (t, J = 8.6 Hz, 2H),
4.56 (s, 2H), 2.43 (s, 3H).
N-Benzyl-N-((4-chlorophenyl)ethynyl)-4-methylbenzenesulfon-
amide (1j). Known compound;19 1.38 g (in 4.0 mmol scale); 88%
yield; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.3 Hz, 2H), 7.35−
7.27 (m, 7H), 7.20 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.6 Hz, 2H), 4.57
(s, 2H), 2.43 (s, 3H).
4-Mehyl-N-phenyl-N-(phenylethynyl)benzenesulfonamide (1u).
Known compound;13 500.0 mg (in 5 mmol scale); 29% yield; H
1
NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.3 Hz, 2H), 7.43−7.25 (m,
12H), 2.44 (s, 3H).
N,4-Dimethyl-N-(phenylethynyl)benzenesulfonamide (1v).
7
1
Known compound; 1.3 g (in 5.0 mmol scale); 91% yield; H NMR
(400 MHz, CDCl3) δ 7.84 (d, J = 8.3 Hz, 2H), 7.40−7.33 (m, 4H),
7.31−7.23 (m, 3H), 3.14 (s, 3H), 2.45 (s, 3H).
N-Allyl-4-methyl-N-(phenylethynyl)benzenesulfonamide (1w).
Known compound;13 1.2 g (in 5.0 mmol scale); 77% yield; 1H
NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.3 Hz, 2H), 7.40−7.31 (m,
4H), 7.30−7.24 (m, 3H), 5.86−5.71 (m, 1H), 5.36−5.20 (m, 2H),
4.05 (d, J = 6.4 Hz, 2H), 2.44 (s, 3H).
General Procedure for the Synthesis of Dioxazoles. 5,5-
Dimethyl-1,4,2-dioxazoles 2a−2j were prepared by camphorsulfonic
acid catalyzed reactions of 2,2-dimethoxypropane and the correspond-
ing hydoxamic acids.14 1,4,2-Dioxazol-5-one 2a′ was synthesized by
the reaction of benzohydroxamic acid with 1,1′-carbonyldiimidazole
(CDI).14,15
General Procedure for 2a−2j. In a 100 mL flask, NH2OH·HCl
(10.0 mmol, 0.70 g), K2CO3 (2.0 equiv, 2.76 g), ethyl acetate (40 mL),
and H2O (20 mL) were added in sequence. After cooling to 0 °C, acyl
chloride (5.0 mmol) was added dropwise. The resulting mixture was
then stirred at room temperature for 16 h. The solution was diluted
with water, extracted with ethyl acetate, and dried over anhydrous
MgSO4. Upon removal of the solvent, the crude product was used
directly for the next step without further purification.
In a 100 mL flask, the crude hydoxamic acid was dissolved in DCM
(30 mL). Subsequently, 2,2-dimethoxypropane (15 mmol, 1.8 mL)
and camphorsulfonic acid (5.5 mmol, 1.28 g) were added. The
resulting solution was stirred at room temperature for 3 h. The
reaction was quenched with saturated NaHCO3 solution, extracted
with dichloromethane, and dried over anhydrous MgSO4. Removal of
the solvent and purification by silica gel column chromatography
N-Benzyl-4-methyl-N-(thiophen-2-ylethynyl)benzenesulfonamide
(1k). Known compound;19 1.47 g (in 5.0 mmol scale); 80% yield; H
1
NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.3 Hz, 2H), 7.34−7.28 (m,
7H), 7.22 (d, J = 5.2 Hz, 1H), 7.08 (d, J = 3.6 Hz, 1H), 6.92 (dd, J =
5.2, 3.6 Hz, 1H), 4.58 (s, 2H), 2.45 (s, 3H).
N-Benzyl-4-methyl-N-((triisopropylsilyl)ethynyl)-
benzenesulfonamide (1l). Known compound;13 1.0 g (in 5.0 mmol
scale); 45% yield; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.3 Hz,
2H), 7.32−7.23 (m, 7H), 4.49 (s, 2H), 2.43 (s, 3H), 0.97−0.91 (m,
21H).
N-Benzyl-N-(hex-1-ynyl)-4-methylbenzenesulfonamide (1m).
Known compound;18 5.0 g (in 20 mmol scale); 73% yield; 1H
NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.3 Hz, 2H), 7.33−7.22 (m,
7H), 4.43 (s, 2H), 2.43 (s, 3H), 2.15 (t, J = 6.9 Hz, 2H), 1.39−1.30
(m, 2H), 1.28−1.17 (m, 2H), 0.82 (t, J = 7.3 Hz, 3H).
N-Benzyl-N-(cyclohexylethynyl)-4-methylbenzenesulfonamide
(1n). Known compound;20 1.2 g (in 5.0 mmol scale); 70% yield; H
1
NMR (400 MHz, Acetone-d6) δ 7.79 (d, J = 8.3 Hz, 2H), 7.43 (d, J =
D
DOI: 10.1021/acs.joc.7b00076
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
afforded the dioxazoles 2a−2j (eluent: petroleum ether/ethyl acetate
50/1).
Et3N solution (10 vol % in pentane) and extracted with DCM (3 × 5
mL). The combined organic phase was washed by water and dried
with anhydrous sodium sulfate. Upon removal of the solvent, the crude
product was purified by silica gel column chromatography to give the
desired product 3aa (eluent: petroleum ether/ethyl acetate 10/1).
N-Benzyl-N-(2,5-diphenyloxazol-4-yl)-4-methylbenzenesulfon-
General Procedure for 2a′. In a 250 mL flask, N-hydroxy-
benzamide (15 mmol, 2.06 g) and 1,1′-carbonyldiimidazole (CDI, 15
mmol, 2.43 g) were dissolved in DCM (150 mL). The resulting
mixture was stirred at room temperature for 2 h. The reaction was
quenched with 1 M HCl, extracted with dichloromethane, washed with
water, and dried over anhydrous MgSO4. Removal of the solvent and
direct crystallization produced 2a′ as a white solid.
1
amide (3aa). White solid; 86.2 mg; 90% yield; mp 131−132 °C; H
NMR (400 MHz, CDCl3) δ 7.99−7.90 (m, 2H), 7.86−7.77 (m, 4H),
7.49−7.41 (m, 3H), 7.39−7.26 (m, 5H), 7.22−7.16 (m, 2H), 7.10−
6.99 (m, 3H), 4.62 (s, 2H), 2.48 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3) δ 158.0, 147.8, 144.1, 135.6, 134.9, 132.9, 130.7, 129.6,
129.38, 128.91, 128.85, 128.4, 128.3, 128.0, 127.3, 126.9, 126.4, 125.7,
54.2, 21.8. HRMS (ESI) calcd for C29H25N2O3S [M + H]+ 481.1580,
found 481.1600.
5,5-Dimethyl-3-phenyl-1,4,2-dioxazole (2a). Known compound;7
2.5 g (in 20.0 mmol scale); 71% yield; 1H NMR (400 MHz, CDCl3) δ
7.82−7.76 (m, 2H), 7.48−7.39 (m, 3H), 1.68 (s, 6H).
3-Phenyl-1,4,2-dioxazol-5-one (2a′). Known compound;7 1.7 g (in
15.0 mmol scale); 70% yield; 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J
= 7.2 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.55 (t, J = 7.7 Hz, 2H).
3-(2-Methoxyphenyl)-5,5-dimethyl-1,4,2-dioxazole (2b). Pale yel-
low oil; 200 mg (in 5.0 mmol scale); 20% yield; 1H NMR (400 MHz,
CDCl3) δ 7.70−7.62 (m, 1H), 7.48−7.39 (m, 1H), 7.03−6.96 (m,
2H), 3.94 (s, 3H), 1.67 (s, 6H). 13C {1H} NMR (100 MHz, CDCl3) δ
158.1, 156.8, 132.5, 129.8, 120.3, 113.8, 112.4, 111.5, 55.9, 24.8.
HRMS (ESI) calcd for C11H14NO3 [M + H]+ 208.0968, found
208.0969.
N-Benzyl-4-methyl-N-(2-phenyl-5-o-tolyloxazol-4-yl)benzene-
sulfonamide (3ba). White solid; 81.8 mg; 83% yield; mp 146−147
1
°C; H NMR (400 MHz, CDCl3) δ 7.96−7.85 (m, 4H), 7.48−7.39
(m, 4H), 7.35 (d, J = 8.0 Hz, 2H), 7.30−7.22 (m, 1H), 7.17 (t, J = 7.5
Hz, 1H), 7.14−7.06 (m, 2H), 7.06−6.96 (m, 4H), 4.52 (s, 2H), 2.49
(s, 3H), 1.93 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.6,
149.0, 144.0, 137.8, 135.9, 134.9, 133.8, 130.61, 130.56, 130.3, 129.7,
129.5, 129.3, 128.9, 128.2, 127.8, 127.5, 126.2, 125.7, 54.0, 21.8, 20.3.
HRMS (ESI) calcd for C30H27N2O3S [M + H]+ 495.1737, found
495.1741.
3-(3-Chlorophenyl)-5,5-dimethyl-1,4,2-dioxazole (2c). Pale yellow
1
oil; 430 mg (in 5.0 mmol scale); 41% yield; H NMR (400 MHz,
N-Benzyl-N-(5-(2-methoxyphenyl)-2-phenyloxazol-4-yl)-4-meth-
CDCl3) δ 7.77−7.74 (m, 1H), 7.69−7.65 (m, 1H), 7.46−7.41 (m,
1H), 7.35 (t, J = 7.9 Hz, 1H), 1.68 (s, 6H). 13C {1H} NMR (100 MHz,
CDCl3) δ 157.3, 134.7, 131.3, 130.0, 126.7, 125.5, 124.8, 116.2, 25.0.
HRMS (ESI) calcd for C10H11ClNO2 [M + H]+ 212.0473, found
212.0479.
ylbenzenesulfonamide (3ca). White solid; 94.0 mg; 92% yield; mp
1
176−177 °C; H NMR (400 MHz, CDCl3) δ 7.98−7.93 (m, 2H),
7.92−7.86 (m, 2H), 7.48−7.41 (m, 4H), 7.36−7.29 (m, 3H), 7.10−
6.98 (m, 5H), 6.97−6.90 (m, 1H), 6.80 (d, J = 8.3 Hz, 1H), 4.53 (s,
2H), 3.63 (s, 3H), 2.47 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ
158.7, 157.5, 146.2, 143.7, 136.4, 135.2, 134.3, 131.1, 131.0, 130.4,
129.5, 129.2, 128.8, 128.0, 127.7, 127.5, 126.4, 120.4, 116.3, 111.0,
55.5, 54.0, 21.8. HRMS (ESI) calcd for C30H27N2O4S [M + H]+
511.1686, found 511.1683.
3-(3-Fluorophenyl)-5,5-dimethyl-1,4,2-dioxazole (2d). Pale yellow
1
oil; 230 mg (in 5.0 mmol scale); 24% yield; H NMR (400 MHz,
CDCl3) δ 7.60−7.54 (m, 1H), 7.50−7.44 (m, 1H), 7.43−7.36 (m,
1H), 7.20−7.13 (m, 1H), 1.69 (s, 6H). 13C {1H} NMR (100 MHz,
CDCl3) δ 162.6 (d, J = 246.9 Hz), 157.5 (d, J = 3.3 Hz), 130.5 (d, J =
8.1 Hz), 125.7 (d, J = 8.7 Hz), 122.5 (d, J = 3.3 Hz), 118.3 (d, J = 21.2
Hz), 116.2, 113.8 (d, J = 24.2 Hz), 25.0. 19F NMR (376 MHz, CDCl3)
δ −111.83. HRMS (ESI) calcd for C11H11FNO2 [M + H]+ 196.0768,
found 196.0771.
N-Benzyl-N-(5-(2-fluorophenyl)-2-phenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3da). White solid; 84.8 mg; 85% yield; mp
1
101−102 °C; H NMR (400 MHz, CDCl3) δ 7.99−7.92 (m, 2H),
7.85 (d, J = 8.0 Hz, 2H), 7.74−7.66 (m, 1H), 7.49−7.41 (m, 3H),
7.38−7.27 (m, 3H), 7.15−6.96 (m, 7H), 4.58 (s, 2H), 2.48 (s, 3H).
13C {1H} NMR (100 MHz, CDCl3) δ 159.4 (d, J = 253.9 Hz), 159.1,
5,5-Dimethyl-3-p-tolyl-1,4,2-dioxazole (2e). Pale yellow oil; 500
1
mg (in 5.0 mmol scale); 52% yield; H NMR (400 MHz, CDCl3) δ
144.0, 135.8, 134.8, 134.7, 131.0 (d, J = 8.2 Hz), 130.8, 130.09, 130.07,
129.6, 129.4, 128.9, 128.8, 128.2, 127.9, 127.3 126.5, 124.0 (d, J = 3.6
Hz), 116.0 (d, J = 21.3 Hz), 115.2 (d, J = 13.0 Hz), 54.1, 21.8. 19F
NMR (376 MHz, CDCl3) δ −111.90. HRMS (ESI) calcd for
C29H24FN2O3S [M + H]+ 499.1486, found 499.1502.
7.67 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H), 1.67
(s, 6H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.5, 141.8, 129.4,
126.7, 120.9, 115.4, 25.0, 21.7. HRMS (ESI) calcd for C11H14NO2 [M
+ H]+ 192.1019, found 192.1023.
3-(4-Methoxyphenyl)-5,5-dimethyl-1,4,2-dioxazole (2f). Known
7
1
N-Benzyl-N-(5-(2-bromophenyl)-2-phenyloxazol-4-yl)-4-methyl-
compound; 350 mg (in 5.0 mmol scale); 34% yield; H NMR (400
MHz, CDCl3) δ 7.71 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H),
3.84 (s, 3H), 1.67 (s, 6H).
benzenesulfonamide (3ea). White solid; 93.5 mg; 84% yield; mp
1
180−181 °C; H NMR (400 MHz, CDCl3) δ 8.00−7.93 (m, 2H),
7.92−7.82 (m, 2H), 7.55−7.49 (m, 2H), 7.49−7.41 (m, 3H), 7.36 (d, J
= 7.9 Hz, 2H), 7.33−7.27 (m, 1H), 7.24−7.19 (m, 1H), 7.15−7.10 (m,
1H), 7.09−7.00 (m, 4H), 4.62−4.45 (m, 2H), 2.48 (s, 3H). 13C {1H}
NMR (100 MHz, CDCl3) δ 159.1, 146.9, 144.0, 135.9, 134.8, 133.2,
132.5, 130.9, 130.8, 129.6, 129.2, 128.92, 128.85, 128.3, 128.02,
127.97, 127.4, 127.2, 126.5, 123.3, 54.1, 21.8. HRMS (ESI) calcd for
C29H24BrN2O3S [M + H]+ 559.0686, found 559.0696.
3-(4-Fluorophenyl)-5,5-dimethyl-1,4,2-dioxazole (2g). Known
7
1
compound; 550 mg (in 5.0 mmol scale); 56% yield; H NMR (400
MHz, CDCl3) δ 7.89−7.60 (m, 2H), 7.21−7.04 (m, 2H), 1.68 (s, 6H).
5,5-Dimethyl-3-(4-(trifluoromethyl)phenyl)-1,4,2-dioxazole (2h).
Known compound;7 1.65 g (in 10.0 mmol scale); 67% yield; 1H
NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.1
Hz, 2H), 1.70 (s, 6H).
3-(Furan-2-yl)-5,5-dimethyl-1,4,2-dioxazole (2i). Known com-
pound;7 500 mg (in 5.0 mmol scale); 60% yield; 1H NMR (400
MHz, CDCl3) δ 7.57−7.49 (m, 1H), 6.90−6.81 (m, 1H), 6.54−6.44
(m, 1H), 1.62 (s, 6H).
3-Cyclohexyl-5,5-dimethyl-1,4,2-dioxazole (2j). Known com-
pound;7 300 mg (in 5.0 mmol scale); 33% yield; 1H NMR (400
MHz, CDCl3) δ 2.42−2.30 (m, 1H), 1.96−1.86 (m, 2H), 1.82−1.74
(m, 2H), 1.71−1.63 (m, 1H), 1.55 (s, 6H), 1.50−1.39 (m, 2H), 1.33−
1.25 (m, 3H).
Representative Procedure for the Tf2NH-Catalyzed Cyclo-
addition. In a 10 mL Schlenk flask, 1a (0.2 mmol, 72.2 mg), 2a (0.24
mmol, 1.2 equiv, 42.5 mg), and DCE (1.5 mL) were added in
sequence. Then a solution of Tf2NH (5 mol %, 2.8 mg) in DCE (0.5
mL) was added dropwise to the system. The resulting mixture was
stirred at room temperature for 5 min. The reaction was quenched by
N-Benzyl-N-(5-(3-fluorophenyl)-2-phenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3fa). White solid; 82.7 mg; 83% yield; mp
1
179−180 °C; H NMR (400 MHz, CDCl3) δ 7.98−7.90 (m, 2H),
7.83 (d, J = 8.0 Hz, 2H), 7.89−7.79. (m, 1H), 7.49−7.41 (m, 4H),
7.35 (d, J = 8.0 Hz, 2H), 7.32−7.26 (m, 1H), 7.23−7.16 (m, 2H),
7.12−7.05 (m, 3H), 7.00−6.93 (m, 1H), 4.62 (s, 2H), 2.48 (s, 3H).
13C {1H} NMR (100 MHz, CDCl3) δ 162.7 (d, J = 245.3 Hz), 158.4,
146.6, 144.2, 135.4, 134.7, 133.6, 130.9, 130.1 (d, J = 8.4 Hz), 129.6,
129.4, 129.0, 128.9, 128.8 (d, J = 8.9 Hz), 128.4, 128.1, 127.1, 126.5,
121.4 (d, J = 3.2 Hz), 115.7 (d, J = 21.2 Hz), 112.5 (d, J = 24.2 Hz),
54.2, 21.8. 19F NMR (376 MHz, CDCl3) δ −112.59. HRMS (ESI)
calcd for C29H24FN2O3S [M + H]+ 499.1486, found 499.1494.
N-Benzyl-4-methyl-N-(2-phenyl-5-p-tolyloxazol-4-yl)benzene-
sulfonamide (3ga). White solid; 90.0 mg; 91% yield; mp 197−198
1
°C; H NMR (400 MHz, CDCl3) δ 7.98−7.88 (m, 2H), 7.83 (d, J =
E
DOI: 10.1021/acs.joc.7b00076
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
8.0 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H), 7.48−7.40 (m, 3H), 7.34 (d, J =
7.9 Hz, 2H), 7.24−7.17 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.11−7.04
(m, 3H), 4.63 (s, 2H), 2.47 (s, 3H), 2.35 (s, 3H). 13C {1H} NMR (100
MHz, CDCl3) δ 157.6, 148.0, 144.0, 138.9, 135.6, 135.0, 132.3, 130.5,
129.5, 129.4, 129.2, 128.9, 128.3, 127.9, 127.4, 126.3, 125.65, 124.2,
54.1, 21.8, 21.6. HRMS (ESI) calcd for C30H27N2O3S [M + H]+
495.1737, found 495.1760.
N-Benzyl-N-(5-(4-methoxyphenyl)-2-phenyloxazol-4-yl)-4-
methylbenzenesulfonamide (3ha). White solid; 87.0 mg; 86% yield;
mp 181−182 °C; 1H NMR (400 MHz, CDCl3) δ 7.95−7.89 (m, 2H),
7.84 (dd, J = 8.2, 1.4 Hz, 2H), 7.75 (dd, J = 8.9, 1.7 Hz, 2H), 7.48−
7.42 (m, 3H), 7.35 (d, J = 7.9 Hz, 2H), 7.23−7.16 (m, 2H), 7.12−7.03
(m, 3H), 6.91−6.83 (m, 2H), 4.61 (s, 2H), 3.82 (s, 3H), 2.48 (s, 3H).
13C {1H} NMR (100 MHz, CDCl3) δ 160.1, 157.4, 147.9, 144.0,
143.7, 136.2, 135.9, 130.9, 130.3, 129.6, 129.3, 128.8, 128.5, 128.4,
127.9, 127.8, 126.0, 53.5, 34.1, 30.7, 26.1, 25.9, 21.8. HRMS (ESI)
calcd for C29H31N2O3S [M + H]+ 487.2050, found 487.2074.
N-Benzyl-N-(2,5-diphenyloxazol-4-yl)methanesulfonamide
(3oa). Known compound;7 63.2 mg; 78% yield; 1H NMR (400 MHz,
CDCl3) δ 8.09−7.99 (m, 2H), 7.81−7.70 (m, 2H), 7.54−7.43 (m,
3H), 7.35−7.21 (m, 5H), 7.15−7.02 (m, 3H), 4.81 (s, 2H), 3.19 (s,
3H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.5, 147.4, 134.7, 132.8,
130.9, 129.5, 129.00, 128.97, 128.5, 128.4, 128.2, 127.1, 126.6, 126.4,
125.7, 55.0, 38.6.
N-Benzyl-N-(2,5-diphenyloxazol-4-yl)benzenesulfonamide (3pa).
1
White solid; 82.9 mg; 89% yield; mp 145−146 °C; H NMR (400
MHz, CDCl3) δ 8.05−7.96 (m, 4H), 7.84−7.77 (m, 2H), 7.67 (t, J =
7.5 Hz, 1H), 7.56 (t, J = 7.8 Hz, 2H), 7.50−7.42 (m, 3H), 7.39−7.27
(m, 3H), 7.23−7.15 (m, 2H), 7.12−7.01 (m, 3H), 4.65 (s, 2H). 13C
{1H} NMR (100 MHz, CDCl3) δ 158.0, 147.8, 138.56, 134.8, 133.3,
132.7, 130.7, 129.4, 128.94, 128.88, 128.5, 128.3, 128.0, 127.3, 126.9,
126.4, 125.7, 54.3. HRMS (ESI) calcd for C28H23N2O3S [M + H]+
467.1424, found 467.1432.
135.6, 135.0, 131.5, 130.4, 129.5, 129.4, 128.90, 128.87, 128.3, 127.9,
127.5, 127.3, 126.2, 119.8, 113.9, 55.4, 54.1, 21.8. HRMS (ESI) calcd
for C30H27N2O4S [M + H]+ 511.1686, found 511.1702.
N-Benzyl-N-(5-(4-fluorophenyl)-2-phenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3ia). White solid; 75.0 mg; 76% yield; mp
1
167−168 °C; H NMR (400 MHz, CDCl3) δ 7.97−7.90 (m, 2H),
N-Benzyl-N-(2,5-diphenyloxazol-4-yl)-4-nitrobenzenesulfon-
1
amide (3qa). Yellow solid; 85.5 mg; 84% yield; mp 162−163 °C; H
7.84 (dd, J = 8.3, 1.7 Hz, 2H), 7.81−7.75 (m, 2H), 7.50−7.43 (m,
3H), 7.36 (d, J = 8.0 Hz, 2H), 7.21−7.14 (m, 2H), 7.11−6.98 (m,
5H), 4.61 (s, 2H), 2.48 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ
162.9 (d, J = 249.2 Hz), 158.0, 147.1, 144.2, 135.5, 134.8, 132.5, 130.8,
129.6, 129.4, 128.93, 128.88, 128.3, 128.1, 127.7 (d, J = 8.3 Hz), 127.2,
126.4, 123.2 (d, J = 3.0 Hz), 115.6 (d, J = 22.1 Hz), 54.2, 21.8. 19F
NMR (376 MHz, CDCl3) δ −111.56. HRMS (ESI) calcd for
C29H24FN2O3S [M + H]+ 499.1486, found 499.1492.
NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 2H), 8.13 (d, J = 8.5
Hz, 2H), 7.99−7.87 (m, 2H), 7.74 (d, J = 7.3 Hz, 2H), 7.48 (d, J = 5.3
Hz, 3H), 7.39−7.28 (m, 3H), 7.21−7.14 (m, 2H), 7.12−7.02 (m, 3H),
4.67 (s, 2H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.4, 150.5,
148.0, 144.4, 133.9, 132.0, 131.0, 130.1, 129.5, 129.2, 129.1, 128.6,
128.43, 128.37, 126.9, 126.5, 126.3, 125.7, 124.1, 54.8. HRMS (ESI)
calcd for C28H22N3O5S [M + H]+ 512.1275, found 512.1278.
N-Benzyl-N-(2,5-diphenyloxazol-4-yl)naphthalene-2-sulfon-
N-Benzyl-N-(5-(4-chlorophenyl)-2-phenyloxazol-4-yl)-4-methyl-
1
amide (3ra). White solid; 71.2 mg; 69% yield; mp 160−161 °C; H
benzenesulfonamide (3ja). White solid; 93.1 mg; 91% yield; mp
1
NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 8.03−7.92 (m, 4H), 7.93−
7.86 (m, 2H), 7.83 (d, J = 7.8 Hz, 2H), 7.68 (t, J = 7.5 Hz, 1H), 7.62
(t, J = 7.4 Hz, 1H), 7.47−7.38 (m, 3H), 7.38−7.25 (m, 3H), 7.22−
7.16 (m, 2H), 7.11−6.98 (m, 3H), 4.67 (s, 2H). 13C {1H} NMR (100
MHz, CDCl3) δ 158.0, 147.8, 135.5, 135.3, 134.7, 132.8, 132.3, 130.7,
130.4, 129.6, 129.4, 129.0, 129.0, 128.9, 128.9, 128.5, 128.3, 128.1,
128.0, 127.5, 127.2, 126.9, 126.3, 125.7, 124.2, 54.4. HRMS (ESI)
calcd for C32H25N2O3S [M + H]+ 517.1580, found 517.1580.
167−168 °C; H NMR (400 MHz, CDCl3) δ 7.98−7.89 (m, 2H),
7.82 (d, J = 8.2 Hz, 2H), 7.76−7.70 (m, 2H), 7.49−7.42 (m, 3H), 7.35
(d, J = 8.1 Hz, 2H), 7.32−7.27 (m, 2H), 7.22−7.14 (m, 2H), 7.11−
7.04 (m, 3H), 4.61 (s, 2H), 2.47 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3) δ 158.2, 146.8, 144.2, 135.4, 134.8, 134.6, 133.2, 130.8, 129.6,
129.4, 128.93, 128.85, 128.7, 128.4, 128.1, 127.1, 126.9, 126.4, 125.4,
54.1, 21.8. HRMS (ESI) calcd for C29H24ClN2O3S [M + H]+
515.1191, found 515.1199.
3-(2,5-Diphenyloxazol-4-yl)oxazolidin-2-one (3sa). Known com-
N-Benzyl-4-methyl-N-(2-phenyl-5-(thien-2-yl)oxazol-4-yl)-
benzenesulfonamide (3ka). Blue solid; 91.9 mg; 95% yield; mp 138−
139 °C; 1H NMR (400 MHz, CDCl3) δ 7.96−7.89 (m, 2H), 7.83 (d, J
= 8.2 Hz, 2H), 7.52 (d, J = 3.6 Hz, 1H), 7.49−7.42 (m, 3H), 7.38−
7.30 (m, 3H), 7.25−7.19 (m, 2H), 7.14−7.07 (m, 3H), 7.05−7.00 (m,
1H), 4.60 (s, 2H), 2.49 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ
157.6, 144.7, 144.1, 135.5, 134.9, 131.7, 130.7, 129.6, 129.3, 128.9,
128.8, 128.3, 128.0, 127.9, 127.4, 127.1, 126.9, 126.4, 126.4, 54.0, 21.8.
HRMS (ESI) calcd for C27H23N2O3S2 [M + H]+ 487.1145, found
487.1140.
N-Benzyl-4-methyl-N-(2-phenyloxazol-4-yl)benzenesulfonamide
(3la). Oil; 45.3 mg; 50% yield; 1H NMR (400 MHz, CDCl3) δ 7.94−
7.85 (m, 2H), 7.71−7.63 (m, 3H), 7.45−7.36 (m, 5H), 7.31−7.20 (m,
5H), 4.87 (s, 2H), 2.41 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ
159.6, 144.0, 138.7, 136.4, 136.0, 132.6, 130.7, 129.8, 128.9, 128.8,
128.5, 127.8, 127.7, 127.3, 126.4, 52.1, 21.7. HRMS (ESI) calcd for
C23H21N2O3S [M + H]+ 405.1267, found 405.1275.
7
1
pound; 30.6 mg; 50% yield; H NMR (400 MHz, CDCl3) δ 8.13−
8.04 (m, 2H), 7.74 (d, J = 8.7 Hz, 2H), 7.54−7.44 (m, 5H), 7.37 (t, J =
7.4 Hz, 1H), 4.61 (t, J = 7.9 Hz, 2H), 4.13 (t, J = 7.9 Hz, 2H). 13C
{1H} NMR (100 MHz, CDCl3) δ 158.9, 156.4, 143.7, 131.0, 129.0,
128.9, 127.2, 127.0, 126.5, 125.5, 63.1, 46.3.
N-(4-Bromobenzyl)-N-(2,5-diphenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3ta). White solid; 74.7 mg; 67% yield; mp
1
172−173 °C; H NMR (400 MHz, CDCl3) δ 7.97−7.91 (m, 2H),
7.87−7.78 (m, 4H), 7.49−7.43 (m, 3H), 7.40−7.31 (m, 5H), 7.16 (dd,
J = 8.4, 1.9 Hz, 2H), 7.05 (dd, J = 8.4, 2.3 Hz, 2H), 4.56 (s, 2H), 2.49
(s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.1, 147.8, 144.2,
135.4, 134.0, 132.7, 131.4, 131.0, 130.8, 129.6, 129.1, 129.0, 128.9,
128.6, 127.2, 126.8, 126.4, 125.8, 122.1, 53.6, 21.8. HRMS (ESI) calcd
for C29H24BrN2O3S [M + H]+ 559.0686, found 559.0695.
N-(2,5-Diphenyloxazol-4-yl)-4-methyl-N-phenylbenzenesulfon-
amide (3ua). Known compound;7 89.0 mg; 97% yield; 1H NMR (400
MHz, CDCl3) δ 8.09 (d, J = 7.5 Hz, 2H), 8.07−7.99 (m, 2H), 7.71 (d,
J = 8.2 Hz, 2H), 7.56−7.43 (m, 7H), 7.37 (t, J = 7.4 Hz, 1H), 7.28−
7.18 (m, 5H), 2.45 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ
158.0, 146.6, 144.04, 139.99, 135.5, 134.5, 130.8, 129.3, 129.1, 129.1,
129.0, 127.7, 127.6, 127.4, 127.1, 126.4, 125.6, 21.8.
N-Benzyl-N-(5-butyl-2-phenyloxazol-4-yl)-4-methylbenzene-
1
sulfonamide (3ma). Yellow oil; 55.0 mg; 60% yield; H NMR (400
MHz, CDCl3) δ 7.90−7.82 (m, 2H), 7.77 (d, J = 8.3 Hz, 2H), 7.44−
7.38 (m, 3H), 7.32 (d, J = 8.2 Hz, 2H), 7.29−7.19 (m, 5H), 4.56 (s,
2H), 2.55−2.43 (m, 5H), 1.28−1.21 (m, 2H), 1.17−1.10 (m, 2H),
0.80 (t, J = 7.2 Hz, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 157.9,
151.8, 143.8, 136.0, 135.9, 132.4, 130.2, 129.6, 129.3, 128.8, 128.5,
128.4, 127.9, 127.7, 126.1, 53.4, 29.5, 24.1, 22.4, 21.8, 13.9. HRMS
(ESI) calcd for C27H29N2O3S [M + H]+ 461.1893, found 461.1893.
N-Benzyl-N-(5-cyclohexyl-2-phenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3na). Yellow oil; 44.8 mg; 46% yield; 1H NMR
(400 MHz, CDCl3) δ 7.90−7.83 (m, 2H), 7.81 (d, J = 8.3 Hz, 2H),
7.45−7.38 (m, 3H), 7.33 (d, J = 8.0 Hz, 2H), 7.30−7.20 (m, 5H), 4.55
(s, 2H), 2.63−2.51 (m, 1H), 2.46 (s, 3H), 1.70−1.64 (m, 2H), 1.37−
1.13 (m, 8H). 13C {1H} NMR (100 MHz, CDCl3) δ 157.8, 155.4,
N-(2,5-Diphenyloxazol-4-yl)-N,4-dimethylbenzenesulfonamide
1
(3va). White solid; 60.6 mg; 75% yield; mp 182−183 °C; H NMR
(400 MHz, CDCl3) δ 8.12−8.02 (m, 2H), 8.01−7.94 (m, 2H), 7.88−
7.77 (m, 2H), 7.52−7.43 (m, 5H), 7.40−7.31 (m, 3H), 3.16 (s, 3H),
2.47 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.1, 145.8,
144.1, 135.18, 134.6, 130.8, 129.5, 129.1, 129.0, 128.9, 127.3, 126.4,
125.5, 37.5, 21.8. HRMS (ESI) calcd for C23H21N2O3S [M + H]+
405.1267, found 405.1261.
N-Allyl-N-(2,5-diphenyloxazol-4-yl)-4-methylbenzenesulfon-
1
amide (3wa). White solid; 60.2 mg; 70% yield; mp 120−121 °C; H
F
DOI: 10.1021/acs.joc.7b00076
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
NMR (400 MHz, CDCl3) δ 8.09 (d, J = 7.2 Hz, 2H), 8.02−7.91 (m,
2H), 7.82 (d, J = 8.2 Hz, 2H), 7.51−7.43 (m, 5H), 7.41−7.30 (m,
3H), 5.83−5.67 (m, 1H), 5.10−4.91 (m, 2H), 4.12 (d, J = 6.7 Hz,
2H), 2.47 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.0, 147.4,
144.1, 135.5, 133.2, 131.9, 130.7, 129.5, 129.0, 128.9, 128.8, 127.32,
127.25, 126.4, 125.6, 119.9, 53.2, 21.8. HRMS (ESI) calcd for
C25H23N2O3S [M + H]+ 431.1424, found 431.1420.
N-Benzyl-N-(2-(2-methoxyphenyl)-5-phenyloxazol-4-yl)-4-
methylbenzenesulfonamide (3ab). Oil; 90.9 mg; 89% yield; 1H
NMR (400 MHz, CDCl3) δ 7.88 (dd, J = 8.2, 1.5 Hz, 2H), 7.84−7.76
(m, 3H), 7.42 (t, J = 7.9 Hz, 1H), 7.37−7.29 (m, 4H), 7.29−7.19 (m,
3H), 7.11−7.05 (m, 3H), 7.02 (t, J = 8.2 Hz, 2H), 4.64 (s, 2H), 3.92
(s, 3H), 2.46 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 157.8,
156.9, 147.3, 143.9, 135.6, 135.0, 132.3, 132.0, 130.3, 129.5, 129.3,
128.9, 128.6, 128.3, 128.2, 127.9, 127.1, 125.6, 120.7, 116.5, 112.3,
56.1, 54.1, 21.7. HRMS (ESI) calcd for C30H27N2O4S [M + H]+
511.1686, found 511.1690.
8.1 Hz, 2H), 7.82 (d, J = 7.0 Hz, 4H), 7.71 (d, J = 8.2 Hz, 2H), 7.41−
7.27 (m, 5H), 7.21−7.14 (m, 2H), 7.11−7.01 (m, 3H), 4.63 (s, 2H),
2.48 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 156.5, 148.7,
144.3, 135.4, 134.7, 133.2, 132.2 (q, J = 32.5 Hz), 130.4, 129.6, 129.3,
129.3, 128.9, 128.5, 128.3, 128.1, 126.5, 126.0 (q, J = 3.9 Hz), 125.9,
123.9 (d, J = 272.5 Hz), 54.2, 21.8. 19F NMR (376 MHz, CDCl3) δ
−62.84. HRMS (ESI) calcd for C30H24F3N2O3S [M + H]+ 549.1454,
found 549.1460.
N-Benzyl-N-(2-(fur-2-yl)-5-phenyloxazol-4-yl)-4-methylbenzene-
sulfonamide (3ai). White solid; 85.2 mg; 91% yield; mp 140−141 °C;
1H NMR (400 MHz, CDCl3) δ 7.85−7.74 (m, 4H), 7.58−7.52 (m,
1H), 7.38−7.27 (m, 5H), 7.23−7.17 (m, 2H), 7.12−7.04 (m, 3H),
7.01−6.94 (m, 1H), 6.58−6.50 (m, 1H), 4.62 (s, 2H), 2.46 (s, 3H).
13C {1H} NMR (100 MHz, CDCl3) δ 150.9, 147.3, 144.7, 144.3,
142.6, 135.3, 134.8, 132.5, 129.7, 129.3, 129.0, 128.8, 128.4, 128.3,
128.0, 126.5, 125.7, 112.1, 53.9, 21.8. HRMS (ESI) calcd for
C27H23N2O4S [M + H]+ 471.1373, found 471.1385.
N-Benzyl-N-(2-cyclohexyl-5-phenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3aj). White solid; 47.8 mg; 50% yield; mp
127−128 °C; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.3 Hz, 2H),
7.72 (d, J = 7.1 Hz, 2H), 7.35−7.25 (m, 4H), 7.28−7.20 (m, 1H),
7.20−7.13 (m, 2H), 7.11−7.03 (m, 3H), 4.56 (s, 2H), 2.81−2.64 (m,
1H), 2.44 (s, 3H), 2.00−1.90 (m, 2H), 1.83−1.73 (m, 2H), 1.72−1.63
(m, 1H), 1.61−1.48 (m, 2H), 1.45−1.21 (m, 3H). 13C {1H} NMR
(100 MHz, CDCl3) δ 164.7, 146.7, 144.0, 135.4, 135.0, 131.0, 129.5,
129.3, 128.7, 128.4, 128.3, 128.2, 127.9, 127.2, 125.4, 53.9, 37.5, 30.5,
25.8, 25.4, 21.7. HRMS (ESI) calcd for C29H31N2O3S [M + H]+
487.2050, found 487.2054.
Gram-Scale Experiment. Acid Catalysis. In a 50 mL Schlenk
flask, 1a (2.7 mmol, 0.98 g), 2a (3.2 mmol, 1.2 equiv, 0.57 g), and
DCE (30 mL) were added in sequence. Then Tf2NH (5 mol %, 38
mg) or TfOH (5 mol %, 12 μL) was introduced. The resulting mixture
was stirred at room temperature for 5 min (Tf2NH as catalyst) or 20
min (TfOH as catalyst). The reaction was quenched by Et3N solution
(10 vol % in pentane) and extracted with DCM (3 × 20 mL). The
combined organic phase was washed by water (3 × 20 mL) and dried
with anhydrous sodium sulfate. Removal of the solvent and direct
crystallization in DCM/petroleum ether afforded the desired product
3aa (1.09 g, 84%, Tf2NH as catalyst or 1.05 g, 81%, TfOH as catalyst).
Gold Catalysis. In a 50 mL Schlenk flask, 1a (2.7 mmol, 0.98 g), 2a
(3.2 mmol, 1.2 equiv, 0.57 g), and DCE (30 mL) were added in
sequence. Then IPrAuNTf2 (5 mol %, 116.9 mg) was introduced. The
resulting mixture was stirred at room temperature for 6 h. Removal of
the solvent and purification by silica gel column chromatography
(eluent: petroleum ether/ethyl acetate 10/1) afforded the desired
product 3aa in 81% yield (1.06 g).
N-Benzyl-N-(2-(3-chlorophenyl)-5-phenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3ac). White solid; 78.0 mg; 76% yield; mp
152−153 °C; 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.85−7.77
(m, 5H), 7.44−7.29 (m, 7H), 7.21−7.15 (m, 2H), 7.09−7.03 (m, 3H),
4.62 (s, 2H), 2.49 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ
156.6, 148.3, 144.2, 135.4, 135.0, 134.7, 133.0, 130.6, 130.3, 129.6,
129.3, 129.1, 128.87, 128.85, 128.5, 128.3, 128.0, 126.6, 126.4, 125.8,
124.3, 54.2, 21.8. HRMS (ESI) calcd for C29H24ClN2O3S [M + H]+
515.1191, found 515.1191.
N-Benzyl-N-(2-(3-fluorophenyl)-5-phenyloxazol-4-yl)-4-methyl-
benzenesulfonamide (3ad). White solid; 67.7 mg; 68% yield; mp
1
166−167 °C; H NMR (400 MHz, CDCl3) δ 7.86−7.78 (m, 4H),
7.75−7.70 (m, 1H), 7.64−7.59 (m, 1H), 7.46−7.40 (m, 1H), 7.38−
7.27 (m, 5H), 7.20−7.13 (m, 3H), 7.10−7.03 (m, 3H), 4.62 (s, 2H),
2.49 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 163.0 (d, J = 246.8
Hz), 156.8, 148.2, 144.2, 135.4, 134.8, 133.0, 130.7 (d, J = 8.3 Hz),
129.6, 129.4, 129.2 (d, J = 8.5 Hz), 129.1, 128.9 128.5, 128.3, 128.0,
126.7, 125.8, 122.0 (d, J = 3.0 Hz), 117.7 (d, J = 21.4 Hz), 113.3 (d, J
= 24.0 Hz), 54.2, 21.8. 19F NMR (376 MHz, CDCl3) δ −111.93.
HRMS (ESI) calcd for C29H24FN2O3S [M + H]+ 499.1486, found
499.1495.
N-Benzyl-4-methyl-N-(5-phenyl-2-p-tolyloxazol-4-yl)benzene-
sulfonamide (3ae). White solid; 93.6 mg; 95% yield; mp 126−127
1
°C; H NMR (400 MHz, CDCl3) δ 7.97−7.77 (m, 6H), 7.38−7.24
(m, 7H), 7.24−7.16 (m, 2H), 7.12−7.00 (m, 3H), 4.62 (s, 2H), 2.48
(s, 3H), 2.42 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3) δ 158.2,
147.4, 144.0, 141.0, 135.6, 134.9, 132.7, 129.62, 129.55, 129.4, 128.9,
128.7, 128.4, 128.3, 128.0, 127.0, 126.3, 125.6, 124.7, 54.1, 21.8, 21.7.
HRMS (ESI) calcd for C30H27N2O3S [M + H]+ 495.1737, found
495.1739.
N-Benzyl-N-(2-(4-methoxyphenyl)-5-phenyloxazol-4-yl)-4-
methylbenzenesulfonamide (3af). White solid; 96.0 mg; 94% yield;
mp 120−121 °C; 1H NMR (400 MHz, CDCl3) δ 7.89−7.82 (m, 4H),
7.79 (d, J = 7.5 Hz, 2H), 7.34−7.28 (m, 4H), 7.27−7.23 (m, 1H),
7.21−7.17 (m, 2H), 7.07−7.02 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 4.62
(s, 2H), 3.82 (s, 3H), 2.45 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3) δ 161.6, 158.1, 147.1, 144.0, 135.6, 134.9, 132.7, 129.5, 129.3,
128.9, 128.6, 128.3, 128.2, 128.0, 127.9, 127.0, 125.5, 120.0, 114.3,
55.5, 54.1, 21.7. HRMS (ESI) calcd for C30H27N2O4S [M + H]+
511.1686, found 511.1695.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.7b00076.
Structures of ynamides, structures of dioxazoles, copies of
NMR spectroscopy (PDF)
AUTHOR INFORMATION
N-Benzyl-N-(2-(4-fluorophenyl)-5-phenyloxazol-4-yl)-4-methyl-
■
benzenesulfonamide (3ag). White solid; 80.9 mg; 81% yield; mp
Corresponding Authors
*E-mail: xcli@dicp.ac.cn (X.L.).
*E-mail: bswan@dicp.ac.cn (B.W.).
1
169−170 °C; H NMR (400 MHz, CDCl3) δ 7.96−7.89 (m, 2H),
7.87−7.74 (m, 4H), 7.38−7.25 (m, 5H), 7.21−7.10 (m, 4H), 7.09−
6.99 (m, 3H), 4.61 (s, 2H), 2.48 (s, 3H). 13C {1H} NMR (100 MHz,
CDCl3) δ 164.3 (d, J = 251.5 Hz), 157.2, 147.8, 144.1, 135.5, 134.8,
132.8, 129.6, 129.3, 128.91, 128.88, 128.48 (d, J = 8.6 Hz), 128.45,
128.3, 128.0, 126.8, 125.7, 123.7 (d, J = 3.3 Hz), 116.1 (d, J = 22.2
Hz), 54.1, 21.8. 19F NMR (376 MHz, CDCl3) δ −108.85. HRMS
(ESI) calcd for C29H24FN2O3S [M + H]+ 499.1486, found 499.1493.
N-Benzyl-4-methyl-N-(5-phenyl-2-(4-(trifluoromethyl)phenyl)-
oxazol-4-yl)benzenesulfonamide (3ah). White solid; 93.1 mg; 85%
ORCID
Boshun Wan: 0000-0002-7001-6214
Author Contributions
§Y.Z. and Y.H. contributed equally.
Notes
1
yield; mp 112−113 °C; H NMR (400 MHz, CDCl3) δ 8.04 (d, J =
The authors declare no competing financial interest.
G
DOI: 10.1021/acs.joc.7b00076
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
soluble in DCE, making it troublesome to weigh the catalyst (0.9 μL)
in a 0.2 mmol scale reaction. Thus the catalytic reactivity of TfOH was
further demonstrated in a gram-scale reaction.
(13) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera, E.
L. Org. Lett. 2004, 6, 1151.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (No. 21572225) is gratefully acknowl-
edged.
(14) Park, Y.; Park, K. T.; Kim, J. G.; Chang, S. J. Am. Chem. Soc.
2015, 137, 4534.
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(11) The prices of IPrAuNTf2, Tf2NH, and TfOH in Sigma-Aldrich
are $320/mmol, $7.3/mmol, and $0.23/mmol, respectively.
(12) In principle, a much cheaper TfOH is preferred to be used as a
catalyst to examine the substrate scope in view of its comparable
reactivity. However, we would like to note that TfOH is partially
H
DOI: 10.1021/acs.joc.7b00076
J. Org. Chem. XXXX, XXX, XXX−XXX