Construction of 1-Naphthols via Benzannulation Based on the Reaction of Aryl tert-Butyl Ynol Ethers with Ynamides or Ynol Ethers

Article abstract of DOI:10.1021/acs.joc.5b01858

A new version of benzannulation featuring the use of aromatic tert-butyl ynol ethers as the convenient precursors for arylketenes has been developed. Both ynamides and ynol ethers undergo this reaction smoothly, giving 3-amino and 3-alkoxy 1-naphthols in

Full text of DOI:10.1021/acs.joc.5b01858

Article
pubs.acs.org/joc
Construction of 1‑Naphthols via Benzannulation Based on the
Reaction of Aryl tert-Butyl Ynol Ethers with Ynamides or Ynol Ethers
Yihui Bai, Jing Yin, Zhicheng Liu, and Gangguo Zhu*
Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China
*
S Supporting Information
ABSTRACT: A new version of benzannulation featuring the
use of aromatic tert-butyl ynol ethers as the convenient
precursors for arylketenes has been developed. Both ynamides
and ynol ethers undergo this reaction smoothly, giving 3-
amino and 3-alkoxy 1-naphthols in good to excellent yields
under the heated reaction conditions. The high efficiency, excellent regioselectivity, good functional group compatibility, and
broad substrate scope render this reaction particularly valuable for organic synthesis.
INTRODUCTION
and efficient method for assembling aromatic compounds
(Scheme 1a−c). It typically depends on the [2 + 2]
cycloaddition of alkynes with vinylketenes resulting from
cyclobutenones, diazo ketones, or Fischer carbenes, respec-
■
Naphthol and its derivatives are privileged scaffolds in a variety
of natural products, pharmaceutical reagents, and highly valued
chemicals. For instance, mollugin (A, Figure 1) is found to
Scheme 1. Benzannulation Strategy Featuring Ketene
Intermediates
Figure 1. Selected bioactive compounds containing 1-naphthol and its
derivatives.
possess significant antiviral activity against the hepatitis B
1
virus. Rubioncolin B (B, Figure 1), a compound isolated from
the roots of Rubia oncotricha and R. cordifolia, has shown a
2
potent cytotoxic and antitumor activity. Other noteworthy
3
examples include gossypol (C, Figure 1), an anti-cancer
reagent, and rifampicin (D, Figure 1), a medicine for the
treatment of mycobacterium infections, including tuberculosis
4
and Hansen’s disease. As such, the invention of new methods
for the synthesis of naphthols with certain substitution patterns
5
is of significant importance. While a number of protocols are
available for this purpose, few methods provide a rapid and
regiocontrolled approach to 1-naphthols.
6
The benzannulation strategy, well developed by Danheiser,
Received: August 11, 2015
7
8
9
Moore, Wulff, and others, has stood out as a straightforward
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b01858
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The Journal of Organic Chemistry
Article
tively, followed by a four electron electrocyclic cleavage/six
electron electrocyclic closure/tautomerization domino process.
Indeed, this method has been successfully applied to the total
toluene, improved the yield to 87% (Table 1, entries 4−9). In
contrast, a diminished yield was observed when the reaction
was carried out under an air atmosphere or at a lower
temperature (Table 1, entries 10 and 11). As such, the further
10
synthesis of a variety of natural products. However, most of
the preceding methods have focused on the construction of
phenols and related compounds, while less attention has been
paid to the access of naphthols. Furthermore, there are only
limited types of ketene precursors for this annulation,
consequently, the exploration of novel benzannulation using
readily accessible and benchtop stable starting materials as
ketene equivalents is highly desirable. A recent work done by
substrate screening was conducted in dioxane under N at 110
2
°C for 10 h.
With the optimized reaction conditions in hand, we first
investigated the substrate scope of ynamides, and the results are
summarized in Table 2. A series of N-sulfonyl ynamides bearing
a
Table 2. Scope of the Synthesis of 3-Amino 1-Naphthols
11
Zhang and Ready stood out as a significant advance in this
field, in which a rapid elaboration of 2-naphthols was achieved
by an intramolecular benzannulation featuring the in situ
generation of arylketenes via a thermolysis of aryl tert-butyl ynol
1
2−14
ethers
(Scheme 1d). In contrast, the intermolecular
version is much more challenging and remains an under-
developed process. Pursuing our recent interest in the
14
transformations of ynol ethers, we report here a new
benzannulation protocol based on aryl tert-butyl ynol ethers,
delivering 3-amino and 3-alkoxy 1-naphthols in a single
synthetic step (Scheme 1e). The high efficiency, excellent
regioselectivity, good functional group compatibility, and
utilization of aromatic tert-butyl ynol ethers as the effective
precursors for labile arylketenes make this reaction very
appealing for synthetic applications.
RESULTS AND DISCUSSION
The initial studies were focused on the reaction between aryl
tert-butyl ynol ether 1a and ynamide 2a, and the results are
summarized in Table 1. By treating 1a (0.25 mmol) and 2a (0.3
■
15
a
Table 1. Optimization of the Reaction Conditions
b
entry
1
2a (equiv)
solvent
toluene
yield (%)
1.2
1.2
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
30
55
c
2
toluene
c
3
toluene
71
c
4
THF
64
c
5
ClCH CH Cl
81
2
2
c
6
MeCN
76
c
7
NMP
trace
trace
87
c
8
DMSO
dioxane
dioxane
dioxane
c
a
9
Reaction conditions: see Table 1; yields refer to the isolated yields.
c
c
,
,
d
e
1
1
0
1
46
66
different substituents were initially surveyed. Halogen atoms
such as F, Cl, and Br were well tolerated to give 1-naphthols
3b−3d in high yields. The electron-rich ynamides 2e−2g
afforded the desired products in particularly good yields, while
the electron-poor substrates 2h and 2i furnished 3h and 3i in
somewhat lower yields, probably due to the reduced
ketenophilicity of latter cases. Moreover, ynamide 2e, derived
from 4-methoxyphenyl acetylene, produced 1-naphthol 3e in
95% yield, while that derived from 2-methoxyphenyl acetylene
led to 3f in a slightly decreased yield (83%). This trans-
formation proceeded successfully with thiophene function,
giving rise to 3j in almost quantitative yield (96%). Alkenyl and
alkyl ynamides, 2k and 2l, for example, participated well in this
reaction to form 3k and 3l in 83% and 74% yield, respectively.
a
Reaction conditions: 1a (0.25 mmol), 2a (0.5 mmol), solvent (2
b
c
mL), under N , 110 °C, 10 h. Isolated yield. 1a was added via a
syringe pump within 2 h. Under an air atmosphere. Run at 80 °C.
2
d
e
mmol) under a nitrogen atmosphere in toluene at 110 °C for
1
0 h, 3-amino 1-naphthol 3a was obtained in 30% yield (Table
, entry 1). We envisioned that a low concentration of ketene
1
intermediates might decrease the undesirable dimerization and
related side reactions. As expected, an improved yield (55%)
was observed when 1a was added via a syringe pump within 2 h
(Table 1, entry 2). Increasing the loading of 2a led to a better
yield (Table 1, entry 3). Meanwhile, the solvent was varied, and
we were delighted to find that the use of dioxane, instead of
B
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Terminal ynamide 2m was also suitable for the production of 1-
naphthol 3m, albeit in a moderate yield. In addition, 3-
partner for this benzannulation, 3-alkoxy 1-naphthol 4a was
generated in 73% yield, and only a trace amount (<5%) of
byproducts resulting from the homocoupling of 1j was
observed. Both electron-rich and electron-poor ynol ethers
1k−1o were compatible with this transformation, affording 3-
alkoxy 1-naphthols 4b−4f in yields of 66−83%. In the
(
phenylethynyl)oxazolidin-2-one (2o) exhibited good reactivity
to generate 3o in a satisfactory yield. In contrast, 2p, an
imidazole-derived ynamide, was found to be unreactive under
the reaction conditions (3p).
2
Subsequently, we turned our attention to the reactivity of
diverse aryl tert-butyl ynol ethers (Table 2). Pleasingly, both
electron-poor and electron-rich ynol ethers were competent
substrates for this reaction, forming the desired products in
good to excellent yields (3q−3v). The reaction occurred
uneventfully with Cl and Br atoms (3q and 3r), which may be
utilized for further functionalization via the transition-metal-
catalyzed cross-coupling reactions.
As such, we have developed a facile and efficient method for
the construction of 3-amino 1-naphthols using a novel
benzannulation featuring the coupling of aryl tert-butyl ynol
ethers with ynamides. Next, we explored the possibility of
assembling 3-alkoxy 1-naphthols via the cross-coupling of aryl
tert-butyl ynol ethers with another class of ynol ethers (Table
meantime, the scope with regard to the R group of ynol
ethers was briefly investigated. Ynol ethers 1p and 1q were also
competent substrates, whereas no detectable product 4j was
observed when 1r was employed as the coupling partner (4h−
4
j). Likewise, this reaction tolerated a wide range of
electronically and sterically different substituents, as well
demonstrated by the assembly of products 4k−4p. The
structure of 1-naphthols 3v and 4a was determined by the X-
16
ray diffraction analysis. Of note, this method generally offers
higher yields when compared with the traditional benzannula-
6b
tion based on diazo ketones.
To probe the reaction mechanism of this benzannulation, the
reaction of 1a and 2a was conducted at 60 °C for 10 h. As a
result, a cyclobutenone compound 5a was isolated in 87% yield,
which was successfully transformed into 3a in 93% yield after
being stirred at 110 °C for 10 h (Scheme 2). Similarly, the
production of 1-naphthol 4g was achieved via the identical
sequence. These results indicate that cyclobutenones may be
the key intermediates for this new benzannulation reaction.
3). Pleasingly, using ynol ether 1j instead of 2a as the alkyne
a
Table 3. Scope of the Access of 3-Alkoxy 1-Naphthols
6
,7,11
In light of the above results and previous reports,
a
possible mechanism for this new variant of benzannulation is
proposed in Scheme 3. The reaction begins from the H[1,5]-
11,17
shift
to deliver an arylketene intermediate I accompanied
by the extrusion of isobutylene, which undergoes a [2 + 2]
cycloaddition with ynamides or ynol ethers to form the
cyclobutenone species II in a regiocontrolled manner. The
polarization of the C−C triple bonds of ynamides or ynol
ethers may account for the observed regioselectivity. Then, the
cyclobutenone species II undergoes the four electron electro-
cyclic cleavage/six electron electrocyclic closure/tautomeriza-
tion domino process to produce polysubstituted 1-naphthols
under the heated conditions.
CONCLUSION
■
In summary, we have realized a new benzannulation protocol
featuring the use of readily accessible aryl tert-butyl ynol ethers
as suitable precursors for labile arylketene intermediates. Both
ynamides and ynol ethers can serve as the alkyne components
for this annulation to form 3-amino and 3-alkoxy 1-naphthols in
good to excellent yields with excellent regioselectivity. A wide
selection of functional groups such as F, Cl, Br, NO , CN, CF ,
2
3
a
Reaction conditions: see Table 1; yields refer to the isolated yields.
OMe, oxazolidinyl, (hetero)aryl, alkenyl, and alkyl substituents
Scheme 2. Preliminary Studies on the Reaction Mechanism
C
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The Journal of Organic Chemistry
Article
Scheme 3. A Plausible Mechanism
−
1
are well tolerated. Further investigations on the synthetic
application of this protocol are currently underway.
1571, 1491, 1447, 1315, 1122 cm ; HRMS (ESI) calcd for
+
C H ClNNaO S (M + Na) 384.0437, found 384.0423.
18
16
3
Compound 3d. White solid, 82 mg, 81% yield, mp: 165−
1
EXPERIMENTAL SECTION
168 °C; H NMR (600 MHz, DMSO-d
8
6
) δ 9.31 (s, 1H), 8.27−
■
.22 (m, 1H), 7.97−7.93 (m, 1H), 7.69 (s, 1H), 7.65 (d, J = 8.5
General. Unless otherwise noted, materials obtained from
commercial suppliers were used directly without further
purification. Dioxane, toluene, and THF were distilled from
sodium prior to use. Column chromatography was carried out
using silica gel (300−400 mesh) with petroleum ethers/EtOAc
Hz, 2H), 7.60−7.55 (m, 2H), 7.32 (d, J = 8.1 Hz, 2H), 2.98 (s,
3
1
1
H), 2.95 (s, 3H); 13C NMR (151 MHz, DMSO-d ) δ 151.0,
6
39.3, 135.3, 133.7, 133.6, 131.1, 128.2, 127.4, 126.4, 125.3,
23.7, 122.8, 120.9, 118.5, 39.3, 37.9; IR (KBr) 3385, 3033,
−1
1
13
1587, 1486, 1458, 1317, 1127 cm ; HRMS (ESI) calcd for
as the eluent. H and C NMR spectra were measured on a
00 or 400 MHz NMR spectrometer using CDCl or DMSO-
+
C H BrNNaO S (M + Na) 427.9932, found 427.9924.
6
18 16
3
3
Compound 3e. White solid, 85 mg, 95% yield, mp: 168−170
d6 as the solvent (see Supporting Information). The chemical
shifts are given in δ relative to TMS, and the coupling constants
are given in Hertz. The high-resolution mass spectra (HRMS)
analyses were conducted using a TOF MS instrument with an
ESI source. Melting points were measured by a melting point
instrument and were uncorrected.
1
°
=
C; H NMR (600 MHz, DMSO-d ) δ 9.04 (s, 1H), 8.23 (d, J
6
8.4 Hz, 1H), 7.93 (d, J = 7.3 Hz, 1H), 7.64 (s, 1H), 7.60−
7.50 (m, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.3 Hz,
2H), 3.82 (s, 3H), 2.96 (s, 3H), 2.87 (s, 3H); 13C NMR (151
MHz, DMSO-d ) δ 158.8, 151.1, 139.9, 133.4, 132.5, 128.1,
6
General Procedure for the Benzannulation between
Aryl tert-Butyl Ynol Ethers and Ynamides. To a solution of
a (104 mg, 0.5 mmol) in 1 mL of dioxane was added a
127.7, 127.1, 126.2, 125.2, 124.4, 122.8, 118.6, 113.8, 55.5, 39.2,
38.4; IR (KBr) 3463, 3018, 1591, 1567, 1496, 1464, 1323, 1140
−1
+
2
cm ; HRMS (ESI) calcd for C H NNaO S (M + Na)
19 19 4
solution of 1a (44 mg, 0.25 mmol) in 1 mL of dioxane via a
syringe pump at 110 °C (oil bath) within 2 h. After refluxing for
380.0932, found 380.0925.
Compound 3f. White solid, 74 mg, 83% yield, mp: 166−168
1
8
h, the reaction mixture was quenched with water, extracted
°
C; H NMR (400 MHz, CDCl ) δ 8.32−8.26 (m, 1H), 7.86−
3
with EtOAc, washed with brine, dried over anhydrous Na SO ,
2
4
7.80 (m, 1H), 7.58−7.47 (m, 4H), 7.41 (d, J = 7.1 Hz, 1H),
and concentrated. Column chromatography on silica gel
petroleum ether/EtOAc = 2:1) gave 71 mg (yield: 87%) of
7
(
.20−7.14 (m, 1H), 7.10 (d, J = 8.3 Hz, 1H), 5.70 (s, 1H), 3.82
(
3
13
s, 3H), 3.18 (s, 3H), 2.61 (s, 3H); C NMR (100 MHz,
1
a as a white solid, mp: 158−161 °C. H NMR (600 MHz,
CDCl ) δ 157.5, 150.0, 138.9, 133.6, 133.3, 130.5, 127.4, 127.2,
3
CDCl ) δ 8.30−8.24 (m, 1H), 7.90−7.80 (m, 1H), 7.60−7.48
3
126.1, 124.0, 122.7, 121.4, 118.9, 118.8, 111.4, 55.6, 38.8, 37.6;
IR (KBr) 3359, 1539, 1505, 1449, 1324, 1119 cm ; HRMS
13
(
m, 8H), 5.64 (s, 1H), 3.12 (s, 3H), 2.66 (s, 3H); C NMR
−1
(
1
151 MHz, CDCl ) δ 149.7, 138.2, 133.5, 133.4, 131.0, 129.5,
28.8, 127.5, 127.3, 126.3, 123.8, 122.6, 121.9, 119.1, 39.3, 38.2;
+
3
(
ESI) calcd for C H NNaO S (M + Na) 380.0932, found
19
19
4
3
80.0921.
IR (KBr) 3376, 3042, 1594, 1570, 1495, 1441, 1318, 1124
Compound 3g. White solid, 77 mg, 90% yield, mp: 160−
−1
+
cm ; HRMS (ESI) calcd for C H NNaO S (M + Na)
1
1
8
17
3
1
7
63 °C; H NMR (600 MHz, CDCl ) δ 8.30−8.20 (m, 1H),
3
3
50.0827, found 350.0820.
.85−7.80 (m, 1H), 7.58−7.54 (m, 2H), 7.53 (s, 1H), 7.45−
Compound 3b. White solid, 62 mg, 72% yield, mp: 172−
1
7.35 (m, 4H), 5.61 (s, 1H), 3.12 (s, 3H), 2.71 (s, 3H), 2.47 (s,
1
8
2
2
2
74 °C; H NMR (400 MHz, DMSO-d ) δ 9.22 (s, 1H), 8.29−
6
13
3
H); C NMR (151 MHz, CDCl ) δ 149.8, 138.7, 138.2,
3
.20 (m, 1H), 7.96−7.93 (m, 1H), 7.67 (s, 1H), 7.60−7.53 (m,
H), 7.43−7.38 (m, 2H), 7.31−7.26 (m, 2H), 2.98 (s, 3H),
1
33.4, 130.8, 130.2, 130.1, 127.5, 127.3, 126.3, 123.7, 122.6,
13
121.9, 119.0, 39.3, 38.2, 21.4; IR (KBr) 3364, 3016, 1594, 1570,
.92 (s, 3H); C NMR (100 MHz, DMSO-d ) δ 161.9 (d, J =
6
−1
1
498, 1448, 1315, 1129 cm ; HRMS (ESI) calcd for
43.8 Hz), 151.2, 139.6, 133.6, 133.4 (d, J = 8.7 Hz), 132.1 (d, J
+
C H NNaO S (M + Na) 364.0983, found 364.0974.
=
3.3 Hz), 128.2, 127.3, 126.4, 125.3, 123.9, 122.8, 118.6, 115.1
19 19
3
Compound 3h. White solid, 68 mg, 73% yield, mp: 194−
(
1
d, J = 21.2 Hz), 39.2, 38.1; IR (KBr) 3381, 3021, 1593, 1571,
498, 1455, 1316, 1123 cm ; HRMS (ESI) calcd for
1
−
1
196 °C; H NMR (600 MHz, DMSO-d ) δ 9.59 (s, 1H), 8.32
6
+
(d, J = 8.7 Hz, 2H), 8.29 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.3
Hz, 1H), 7.76 (s, 1H), 7.66 (d, J = 8.3 Hz, 2H), 7.64−7.57 (m,
C H FNNaO S (M + Na) 368.0733, found 368.0718.
18
16
3
Compound 3c. White solid, 72 mg, 80% yield, mp: 161−163
1
3
1
2
H), 3.06 (s, 3H), 2.98 (s, 3H); C NMR (151 MHz, DMSO-
°
C; H NMR (400 MHz, DMSO-d ) δ 9.28 (s, 1H), 8.30−8.20
6
(
m, 1H), 8.00−7.90 (m, 1H), 7.68 (s, 1H), 7.60−7.53 (m, 2H),
d
6
) δ 151.1, 146.8, 144.0, 138.9, 133.9, 133.0, 128.3, 127.7,
7
2
1
1
.51 (d, J = 8.5 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 2.98 (s, 3H),
126.6, 125.3, 123.3, 123.2, 122.9, 118.6, 39.4, 37.4; IR (KBr)
3393, 3029, 1594, 1571, 1448, 1321, 1138 cm ; HRMS (ESI)
13
−1
.94 (s, 3H); C NMR (100 MHz, DMSO-d ) δ 151.1, 139.4,
6
+
34.9, 133.6, 133.3, 132.2, 128.2, 128.1, 127.4, 126.4, 125.3,
23.7, 122.8, 118.5, 39.3, 37.9; IR (KBr) 3376, 3055, 1591,
calcd for C H N NaO S (M + Na) 395.0678, found
1
8
16
2
5
395.0657.
D
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The Journal of Organic Chemistry
Article
Compound 3i. White solid, 60 mg, 68% yield, mp: 182−185
Compound 3q. White solid, 67 mg, 74% yield, mp: 163−
1
1
°
C; H NMR (600 MHz, DMSO-d ) δ 9.51 (s, 1H), 8.40−8.20
167 °C; H NMR (400 MHz, CDCl ) δ 8.24 (d, J = 1.8 Hz,
6
3
(
m, 1H), 8.01−7.87 (m, 3H), 7.74 (s, 1H), 7.65−7.50 (m, 4H),
1H), 7.75 (d, J = 8.8 Hz, 1H), 7.61−7.47 (m, 7H), 5.59 (s,
1
3
13
3
1
1
3
.03 (s, 3H), 2.96 (s, 3H); C NMR (151 MHz, DMSO-d ) δ
1H), 3.11 (s, 3H), 2.63 (s, 3H); C NMR (100 MHz, CDCl )
6
3
51.0, 141.7, 139.0, 133.9, 132.7, 132.0, 128.3, 127.6, 126.6,
25.3, 123.7, 122.9, 119.7, 118.6, 110.1, 39.4, 37.6; IR (KBr)
δ 149.0, 138.4, 133.0, 132.3, 131.7, 130.8, 129.6, 129.1, 129.0,
128.2, 124.4, 122.9, 121.9, 119.0, 39.2, 38.3; IR (KBr) 3516,
−1
−1
368, 3029, 1595, 1570, 1495, 1448, 1322, 1138 cm ; HRMS
3067, 1592, 1567, 1490, 1443, 1322, 1147 cm ; HRMS (ESI)
+
+
(
ESI) calcd for C H N NaO S (M + Na) 375.0779, found
calcd for C H ClNNaO S (M + Na) 384.0437, found
1
9
16
2
3
18 16
3
375.0761.
384.0410.
Compound 3j. White solid, 80 mg, 96% yield, mp: 178−180
Compound 3r. White solid, 76 mg, 75% yield, mp: 161−164
1
1
°
7
1
C; H NMR (400 MHz, CDCl ) δ 8.31−8.24 (m, 1H), 7.84−
°C; H NMR (600 MHz, CDCl ) δ 8.43 (s, 1H), 7.69 (d, J =
3
3
.78 (m, 1H), 7.61−7.53 (m, 4H), 7.30−7.22 (m, 2H), 6.11 (s,
8.7 Hz, 1H), 7.65−7.47 (m, 7H), 5.58 (s, 1H), 3.12 (s, 3H),
1
3
13
H), 3.20 (s, 3H), 2.77 (s, 3H); C NMR (100 MHz, CDCl )
2.63 (s, 3H); C NMR (151 MHz, CDCl ) δ 148.9, 138.6,
3
3
δ 151.3, 138.5, 133.8, 133.6, 129.9, 128.6, 127.9, 127.8, 127.5,
133.0, 131.9, 130.9, 130.8, 129.6, 129.1, 129.0, 125.2, 124.8,
1
3
26.5, 123.6, 122.9, 119.4, 114.2, 39.5, 38.1; IR (KBr) 3487,
122.9, 120.5, 119.1, 39.2, 38.3; IR (KBr) 3516, 3066, 1588,
−1
−1
064, 1594, 1569, 1494, 1446, 1321, 1141 cm ; HRMS (ESI)
1564, 1498, 1442, 1323, 1147 cm ; HRMS (ESI) calcd for
calcd for C H NNaO S (M + Na)+ 356.0391, found
C H BrNNaO S (M + Na) 427.9932, found 427.9920.
+
1
6
15
3
2
18 16
3
3
56.0374.
Compound 3s. White solid, 85 mg, 95% yield, mp: 157−159
1
Compound 3k. White solid, 73 mg, 83% yield, mp: 143−
°C; H NMR (600 MHz, CDCl ) δ 7.72 (d, J = 9.0 Hz, 1H),
3
1
1
7
7
3
1
1
1
46 °C; H NMR (400 MHz, CDCl ) δ 8.31−8.25 (m, 1H),
7.60−7.44 (m, 7H), 7.23 (dd, J = 8.9, 2.5 Hz, 1H), 5.58 (s,
3
.80−7.75 (m, 1H), 7.62−7.53 (m, 4H), 7.46−7.34 (m, 5H),
.10 (d, J = 17.0 Hz, 1H), 6.43 (s, 1H), 3.31 (s, 3H), 3.08 (s,
1H), 3.96 (s, 3H), 3.11 (s, 3H), 2.66 (s, 3H); 13C NMR (151
MHz, CDCl ) δ 158.2, 148.6, 135.8, 133.7, 130.9, 129.4, 129.1,
3
H); 13C NMR (100 MHz, CDCl ) δ 150.2, 138.2, 136.3,
128.9, 128.8, 124.8, 122.5, 120.3, 118.9, 100.7, 55.5, 39.4, 38.1;
IR (KBr) 3517, 3012, 1591, 1563, 1499, 1455, 1320, 1150
3
35.1, 133.0, 128.9, 128.6, 127.4, 127.4, 126.7, 126.5, 124.2,
22.8, 122.5, 118.8, 118.1, 39.2, 37.7; IR (KBr) 3385, 3059,
591, 1569, 1496, 1146, 1318, 1128 cm ; HRMS (ESI) calcd
−1
+
cm ; HRMS (ESI) calcd for C H NNaO S (M + Na)
19
19
4
−1
380.0932, found 380.0924.
+
for C H NNaO S (M + Na) 376.0983, found 376.0969.
Compound 3t. White solid, 78 mg, 92% yield, mp: 154−157
20
19
3
1
1
Compound 3l. Yellow oil, 67 mg, 74% yield; H NMR (600
°C; H NMR (400 MHz, CDCl ) δ 8.04 (s, 1H), 7.72 (d, J =
3
MHz, CDCl ) δ 8.09−8.05 (m, 1H), 7.75−7.70 (m, 1H),
8.4 Hz, 1H), 7.61−7.37 (m, 7H), 5.54 (s, 1H), 3.11 (s, 3H),
3
7
3
.48−7.43 (m, 2H), 7.39 (s, 1H), 5.80 (s, 1H), 3.35 (s, 3H),
2.66 (s, 3H), 2.57 (s, 3H); 13C NMR (100 MHz, CDCl ) δ
3
13
.09 (s, 3H), 1.70−1.10 (m, 14H), 0.91 (t, J = 6.9 Hz, 3H); C
149.1, 137.2, 136.3, 133.6, 131.7, 131.0, 129.6, 129.4, 128.7,
127.4, 123.9, 121.9, 121.5, 118.9, 39.3, 38.1, 22.0; IR (KBr)
NMR (151 MHz, CDCl ) δ 150.5, 139.3, 132.2, 127.3, 126.4,
3
−1
1
2
1
26.1, 124.4, 122.8, 121.5, 118.2, 40.1, 35.9, 31.9, 30.1, 29.6,
9.5, 29.3, 26.0, 22.7, 14.2; IR (KBr) 3489, 3011, 1594, 1571,
3517, 3018, 1604, 1566, 1491, 1442, 1323, 1138 cm ; HRMS
+
(ESI) calcd for C H NNaO S (M + Na) 364.0983, found
19
19
3
−
1
491, 1457, 1330, 1144 cm ; HRMS (ESI) calcd for
364.0979.
+
C H NNaO S (M + Na) 386.1766, found 386.1746.
Compound 3u. White solid, 60 mg, 68% yield, mp: 173−
20
29
3
1
Compound 3m. White solid, 33 mg, 53% yield, mp: 118−
177 °C; H NMR (600 MHz, CDCl ) δ 8.67 (s, 1H), 7.94−
3
1
1
1
1
21 °C; H NMR (600 MHz, CDCl ) δ 8.18 (d, J = 8.2 Hz,
7.88 (m, 1H), 7.70−7.45 (m, 7H), 5.78 (s, 1H), 3.14 (s, 3H),
3
H), 7.78 (d, J = 8.1 Hz, 1H), 7.56−7.48 (m, 2H), 7.35 (s,
2.62 (s, 3H); 13C NMR (151 MHz, CDCl ) δ 150.2, 141.4,
3
H), 7.29 (s, 1H), 7.03 (d, J = 1.5 Hz, 1H), 3.43 (s, 3H), 2.94
134.7, 132.7, 132.5, 130.8, 129.7, 129.4, 129.3, 128.7, 127.7,
123.8, 122.9, 119.1, 109.4, 39.1, 38.4; IR (KBr) 3309, 3030,
(
s, 3H); 13C NMR (151 MHz, CDCl ) δ 152.6, 139.1, 134.3,
3
−1
1
27.5, 127.4, 125.7, 123.7, 122.0, 115.4, 108.4, 38.4, 35.2; IR
1627, 1559, 1457, 1318, 1136 cm ; HRMS (ESI) calcd for
−1
+
(
(
2
KBr) 3355, 3061, 1595, 1579, 1451, 1310, 1138 cm ; HRMS
ESI) calcd for C H NNaO S (M + Na) 274.0514, found
C H N NaO S (M + Na) 375.0779, found 375.0779.
19
16
2
3
+
Compound 3v. White solid, 65 mg, 73% yield, mp: 168−
1
2
13
3
1
74.0497.
170 °C; H NMR (400 MHz, DMSO-d ) δ 9.11 (s, 1H), 7.82
6
Compound 3n. White solid, 83 mg, 85% yield, mp: 183−
(d, J = 8.5 Hz, 1H), 7.76 (s, 1H), 7.50−7.45 (m, 3H), 7.41−
1
1
1
6
1
1
1
1
85 °C; H NMR (600 MHz, CDCl ) δ 8.27 (d, J = 8.1 Hz,
7.34 (m, 3H), 7.03 (d, J = 7.7 Hz, 1H), 4.00 (s, 3H), 2.99 (s,
3
H), 7.91 (d, J = 8.0 Hz, 1H), 7.75 (s, 1H), 7.61−7.46 (m,
3H), 2.69 (s, 3H); 13C NMR (100 MHz, DMSO-d ) δ 155.1,
6
H), 7.18−7.10 (m, 4H), 6.97 (d, J = 7.1 Hz, 2H), 5.52 (s,
151.0, 139.0, 136.0, 131.3, 128.2, 127.5, 126.6, 126.4, 125.6,
125.2, 114.9, 112.7, 105.6, 56.1, 39.3, 38.2; IR (KBr) 3420,
1
3
H), 3.03 (s, 3H); C NMR (151 MHz, CDCl ) δ 150.1,
3
−1
40.5, 137.0, 133.3, 132.8, 129.3, 128.9, 128.8, 127.7, 127.4,
26.4, 123.8, 122.7, 122.0, 120.2, 40.1; IR (KBr) 3533, 3051,
3008, 1593, 1536, 1494, 1442, 1320, 1125 cm ; HRMS (ESI)
+
calcd for C H NNaO S (M + Na) 380.0932, found 380.0920
19
19
4
−1
592, 1570, 1490, 1456, 1326, 1145 cm ; HRMS (ESI) calcd
(see Supporting Information). Crystal data for 3v
(C H NO S, 357.41): orthorhombic, space group Pbca, a =
+
for C H NNaO S (M + Na) 412.0983, found 412.0976.
23
19
3
19 19
4
Compound 3o. White solid, 54 mg, 71% yield, mp: 80−83
16.4246(5) Å, b = 11.9941(4) Å, c = 17.9328(5) Å, U =
1
3
°
7
8
C; H NMR (400 MHz, CDCl ) δ 8.30−8.23 (m, 1H), 7.85−
3532.73(19) Å , Z = 8, T = 296(2) K, absorption coefficient
3
−
1
.81 (m, 1H), 7.60−7.49 (m, 8H), 5.70 (s, 1H), 4.14 (t, J =
0.207 mm , reflections collected 28721, independent
reflections 4137 [R(int) = 0.0736], refinement by full-matrix
1
3
.16 Hz, 2H), 3.44 (t, J = 7.72 Hz, 2H); C NMR (100 MHz,
2
CDCl ) δ 157.6, 149.5, 133.6, 133.4, 132.8, 130.3, 129.9, 129.0,
least-squares on F , data/restraints/parameters 4137/0/242,
3
2
1
(
27.6, 127.4, 126.2, 123.7, 122.6, 119.8, 119.0, 62.2, 47.8; IR
goodness-of-fit on F = 1.007, final R indices [I > 2s(I)] R =
1
−1
KBr) 3362, 3058, 1740, 1595, 1570, 1495, 1458, 1211 cm ;
0.0453, wR = 0.1201, R indices (all data) R = 0.0597, wR =
2
1
2
+
−3
HRMS (ESI) calcd for C H NNaO (M + Na) 328.0950,
0.1402, largest diff peak and hole 0.299 and −0.422 e·Å .
Crystallographic data for the structure 3v have been deposited
1
9
15
3
found 328.0922.
E
DOI: 10.1021/acs.joc.5b01858
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
with the Cambridge Crystallographic Data Center as
supplementary publication no. CCDC 1412471.
Hz, 1H), 7.50−7.37 (m, 6H), 6.86 (s, 1H), 5.67 (s, 1H), 4.13
1
3
(q, J = 6.96 Hz, 2H), 2.48 (s, 3H), 1.35 (t, J = 7.0 Hz, 3H); C
General Procedure for the Benzannulation between
Aryl tert-Butyl Ynol Ethers and Ynol Ethers. To a solution
of 1j (73 mg, 0.5 mmol) in 1 mL of dioxane was added a
solution of 1a (44 mg, 0.25 mmol) in 1 mL of dioxane via a
syringe pump at 110 °C for 1 h. After stirring at 110 °C for 6 h,
the reaction mixture was quenched with water, extracted with
EtOAc, washed with brine, dried over anhydrous Na SO , and
NMR (151 MHz, CDCl ) δ 154.9, 149.2, 137.8, 134.2, 130.8,
3
129.9, 129.6, 126.9, 126.2, 122.9, 122.4, 119.9, 114.7, 99.0, 63.8,
21.4, 14.6; IR (KBr) 3527, 3049, 1598, 1576, 1499, 1446, 1129
−1
+
cm ; HRMS (ESI) calcd for C H O (M + H) 279.1385,
19
19
2
found 279.1369.
Compound 4f. White solid, 55 mg, 66% yield, mp: 96−98
1
2
4
°C; H NMR (600 MHz, CDCl ) δ 8.19 (d, J = 8.3 Hz, 1H),
3
concentrated. Column chromatography on silica gel (petroleum
7
8
1
.82 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.2 Hz, 1H), 7.61 (d, J =
.0 Hz, 2H), 7.52−7.50 (m, 1H), 7.41−7.38 (m, 1H), 6.88 (s,
H), 5.45 (s, 1H), 4.13 (q, J = 7.0 Hz, 2H), 1.34 (t, J = 7.0 Hz,
ether/EtOAc = 20:1) gave 48 mg (yield: 73%) of 4a as a white
1
solid, mp: 93−95 °C (see Supporting Information). H NMR
13
(
600 MHz, CDCl ) δ 8.21 (d, J = 8.3 Hz, 1H), 7.74 (d, J = 8.2
3
3H); C NMR (151 MHz, CDCl ) δ 154.3, 149.1, 136.9,
3
Hz, 1H), 7.58−7.46 (m, 6H), 7.38 (t, J = 7.5 Hz, 1H), 6.87 (s,
1
3
34.6, 131.6, 130.0 (q, J = 32.5 Hz), 127.4, 126.4, 126.0 (q, J =
.7 Hz), 124.1 (q, J = 270.1 Hz), 123.3, 122.4, 119.9, 113.5,
1
3
1
1
1
2
2
1
2
H), 5.66 (s, 1H), 4.13 (q, J = 6.9 Hz, 2H), 1.34 (t, J = 6.9 Hz,
H); 13C NMR (151 MHz, CDCl ) δ 154.8, 149.1, 134.4,
3
99.2, 63.9, 14.5; IR (KBr) 3228, 3061, 1599, 1578, 1498, 1443,
32.8, 131.0, 129.2, 128.1, 127.0, 126.3, 123.1, 122.5, 120.0,
14.9, 99.1, 63.9, 14.6; IR (KBr) 3488, 3049, 1595, 1575, 1503,
−1
+
1
3
107 cm ; HRMS (ESI) calcd for C H F O (M + H)
19 16 3 2
33.1102, found 333.1073.
Compound 4g. White solid, 64 mg, 88% yield, mp: 86−89
°C; H NMR (600 MHz, CDCl ) δ 8.26 (d, J = 8.3 Hz, 1H),
−1
+
455, 1127 cm ; HRMS (ESI) calcd for C H O (M + H)
1
8
17
2
65.1229, found 265.1221. Crystal data for 4a (C H O ,
1
18
16
2
3
64.31): monoclinic, space group P2 /N, a = 12.9443(8) Å, b =
1
7
.77 (d, J = 8.2 Hz, 1H), 7.57−7.43 (m, 7H), 7.21 (s, 1H), 5.74
13
3
0.3400(6) Å, c = 21.8826(13) Å, U = 2909.3(3) Å , Z = 8, T =
96(2) K, absorption coefficient 0.078 mm , reflections
(
s, 1H), 1.23 (s, 9H); C NMR (151 MHz, CDCl ) δ 151.9,
−
1
3
1
1
1
48.9, 134.0, 133.8, 131.4, 129.0, 127.9, 126.8, 126.7, 123.9,
22.5, 121.1, 119.5, 111.0, 79.9, 29.0; IR (KBr) 3528, 3052,
collected 19243, independent reflections 6554 [R(int) =
2
0
.0905], refinement by full-matrix least-squares on F , data/
−1
597, 1575, 1495, 1456, 1134 cm ; HRMS (ESI) calcd for
2
restraints/parameters 6554/0/365, goodness-of-fit on F
=
+
C H NaO (M + Na) 315.1361, found 315.1378.
20
20
2
1
.071, final R indices [I > 2s(I)] R = 0.0739, wR = 0.1831, R
1
1
2
Compound 4h. Colorless oil, 46 mg, 70% yield; H NMR
400 MHz, CDCl ) δ 8.18 (d, J = 8.3 Hz, 1H), 7.75 (d, J = 8.2
indices (all data) R = 0.1166, wR = 0.2278, largest diff peak
1
2
(
−3
3
and hole 0.253 and −0.419 e·Å . Crystallographic data for the
structure 4a have been deposited with the Cambridge
Crystallographic Data Center as supplementary publication
no. CCDC 1412472.
Hz, 1H), 7.52−7.46 (m, 1H), 7.39−7.34 (m, 5H), 6.87 (s, 1H),
13
5
.62 (s, 1H), 3.87 (s, 3H), 2.47 (s, 3H); C NMR (100 MHz,
CDCl ) δ 155.6, 149.2, 138.1, 134.2, 130.8, 130.2, 129.4, 127.0,
3
1
26.3, 123.1, 122.4, 120.0, 114.4, 97.9, 55.7, 21.4; IR (KBr)
Compound 4b. White solid, 64 mg, 75% yield, mp: 120−
−1
1
3524, 3052, 1597, 1576, 1499, 1459, 1130 cm ; HRMS (ESI)
calcd for C H O (M + H) 265.1229, found 265.1219.
1
1
3
22 °C; H NMR (400 MHz, CDCl ) δ 8.17 (d, J = 8.3 Hz,
3
+
18
17
2
H), 7.73−7.66 (m, 3H), 7.52−7.46 (m, 1H), 7.40−7.32 (m,
1
Compound 4i. Colorless oil, 57 mg, 74% yield; H NMR
(400 MHz, CDCl ) δ 8.14−8.08 (m, 1H), 7.65−7.59 (m, 1H),
.44−7.39 (m, 2H), 7.29−7.25 (m, 1H), 6.98 (d, J = 7.5 Hz,
H), 6.84 (s, 1H), 5.48 (s, 1H), 4.11 (q, J = 7.0 Hz, 2H), 1.33
1
3
3
(
t, J = 7.0 Hz, 3H); C NMR (100 MHz, CDCl ) δ 154.4,
3
7
1
1
1
1
49.0, 134.4, 132.8, 132.4, 131.7, 127.2, 126.3, 123.2, 122.4,
22.3, 119.9, 113.6, 99.1, 63.9, 14.6; IR (KBr) 3489, 3052,
H), 6.91−6.84 (m, 3H), 5.36 (s, 1H), 2.89−2.82 (m, 2H),
−1
2.38 (s, 3H), 1.70−1.64 (m, 2H), 1.51−1.41 (m, 2H), 0.97 (t, J
596, 1575, 1503, 1488, 1128 cm ; HRMS (ESI) calcd for
+
= 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl ) δ 157.4, 154.5,
3
C H BrNaO (M + Na) 365.0153, found 365.0144.
18
15
2
1
49.8, 140.0, 132.9, 129.5, 126.9, 126.2, 124.1, 123.9, 121.3,
Compound 4c. White solid, 61 mg, 83% yield, mp: 127−130
1
121.1, 119.6, 116.1, 115.9, 106.9, 31.6, 23.8, 22.8, 21.5, 14.0; IR
°
C; H NMR (600 MHz, CDCl ) δ 8.19 (d, J = 8.2 Hz, 1H),
7
3
−
1
(
(
KBr) 3503, 3027, 1578, 1485, 1457, 1244, 1135 cm ; HRMS
.73 (d, J = 8.2 Hz, 1H), 7.49−7.47 (m, 1H), 7.40−7.35 (m,
H), 7.09 (d, J = 8.1 Hz, 2H), 6.85 (s, 1H), 5.68 (s, 1H), 4.13
+
ESI) calcd for C H O (M + H) 307.1698, found 307.1689.
3
(
21 23
2
1
13
Compound 4k. Colorless oil, 48 mg, 65% yield; H NMR
q, J = 6.9 Hz, 2H), 3.91 (s, 3H), 1.35 (t, J = 6.8 Hz, 3H); C
(
7
1
600 MHz, CDCl ) δ 7.80−7.78 (m, 1H), 7.69−7.67 (m, 1H),
NMR (151 MHz, CDCl ) δ 159.3, 155.0, 149.2, 134.2, 132.2,
3
3
.37−7.33 (m, 4H), 7.28−7.24 (m, 1H), 6.85 (s, 1H), 5.66 (s,
1
5
28.7, 127.4, 126.9, 126.2, 123.0, 122.4, 119.9, 114.7, 99.0, 63.8,
5.3, 14.6; IR (KBr) 3496, 3064, 1598, 1570, 1509, 1447, 1128
H), 4.11 (q, J = 7.0 Hz, 2H), 2.47 (s, 3H), 1.34 (t, J = 7.0 Hz,
13
cm ; HRMS (ESI) calcd for C H NaO (M + Na)+
−
1
3H); C NMR (151 MHz, CDCl ) δ 159.2 (d, J = 241.9 Hz),
3
1
9
18
3
1
1
54.3 (d, J = 2.3 Hz), 148.6 (d, J = 5.0 Hz), 138.0, 131.0, 130.7,
30.0, 129.2, 128.3 (d, J = 8.5 Hz), 120.3 (d, J = 8.8 Hz), 116.9
3
17.1154, found 317.1147.
Compound 4d. Yellow oil, 54 mg, 74% yield; H NMR (600
1
(
1
d, J = 25.2 Hz), 115.6, 106.4 (d, J = 22.3 Hz), 99.0, 63.9, 21.4,
MHz, CDCl ) δ 8.26−8.20 (m, 1H), 7.74−7.72 (m, 1H),
3
−1
4.6; IR (KBr) 3526, 3021, 1579, 1504, 1437, 1150, 1081 cm ;
7
6
1
1
1
.50−7.44 (m, 2H), 7.40−7.35 (m, 2H), 7.13−7.10 (m, 2H),
+
.89 (s, 1H), 5.84 (s, 1H), 4.15−4.12 (m, 2H), 3.85 (s, 3H),
HRMS (ESI) calcd for C19
H
18FO
2
(M + H) 297.1291, found
1
3
.32 (t, J = 6.9 Hz, 3H); C NMR (151 MHz, CDCl ) δ 157.3,
297.1277.
3
1
55.2, 149.6, 134.5, 133.2, 129.7, 126.8, 126.2, 122.9, 122.6,
Compound 4l. Colorless oil, 60 mg, 67% yield; H NMR
21.4, 121.2, 120.5, 112.0, 111.6, 99.4, 63.9, 55.8, 14.6; IR
(600 MHz, CDCl ) δ 8.36−8.34 (m, 1H), 7.59−7.52 (m, 2H),
3
−1
(
(
3
KBr) 3527, 3066, 1594, 1574, 1491, 1458, 1113 cm ; HRMS
ESI) calcd for C H NaO (M + Na) 317.1154, found
17.1146.
Compound 4e. Colorless oil, 54 mg, 77% yield; H NMR
600 MHz, CDCl ) δ 8.19 (d, J = 8.3 Hz, 1H), 7.72 (d, J = 8.2
7.38−7.34 (m, 4H), 6.81 (s, 1H), 5.68 (s, 1H), 4.12 (q, J = 7.0
+
13
Hz, 2H), 2.48 (s, 3H), 1.34 (t, J = 7.0 Hz, 3H); C NMR (151
1
9
18
3
MHz, CDCl ) δ 155.3, 148.4, 138.1, 132.7, 130.8, 130.7, 130.1,
3
1
130.1, 127.9, 124.9, 121.4, 121.1, 116.5, 98.9, 63.9, 21.4, 14.6;
−1
(
IR (KBr) 3523, 3024, 1587, 1572, 1491, 1453, 1136 cm ;
3
F
DOI: 10.1021/acs.joc.5b01858
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
HRMS (ESI) calcd for C H BrNaO (M + Na) 379.0310,
Article
+
1
9
17
2
AUTHOR INFORMATION
Corresponding Author
gangguo@zjnu.cn
■
found 379.0300.
Compound 4m. White solid, 63 mg, 82% yield, mp: 112−
*
1
1
1
2
2
15 °C; H NMR (600 MHz, CDCl ) δ 7.64 (d, J = 8.9 Hz,
3
Notes
H), 7.50−7.49 (m, 1H), 7.38−7.36 (m, 4H), 7.18 (dd, J = 8.9,
The authors declare no competing financial interest.
.6 Hz, 1H), 6.84 (s, 1H), 5.64 (s, 1H), 4.10 (q, J = 7.0 Hz,
H), 3.96 (s, 3H), 2.48 (s, 3H), 1.33 (t, J = 7.0 Hz, 3H); 13
C
ACKNOWLEDGMENTS
NMR (151 MHz, CDCl ) δ 155.9, 153.2, 148.1, 137.8, 130.8,
■
3
We are grateful for the financial support from the Science
Technology Department of Zhejiang Province (2015C31030),
Natural Science Foundation of Zhejiang Province
1
5
1
3
30.0, 129.7, 129.4, 127.9, 120.4, 119.5, 115.3, 100.9, 99.3, 63.9,
5.4, 21.4, 14.7; IR (KBr) 3523, 3021, 1587, 1575, 1491, 1453,
−1
+
186 cm ; HRMS (ESI) calcd for C H NaO (M + Na)
2
0
20
3
(
LR12B02001 and LY14B020002), and National Natural
31.1310, found 331.1298.
Compound 4n. White solid, 55 mg, 76% yield, mp: 98−101
Science Foundation of China (21172199).
1
°
C; H NMR (600 MHz, CDCl ) δ 7.98 (s, 1H), 7.65 (d, J =
8
3
REFERENCES
.3 Hz, 1H), 7.39−7.36 (m, 4H), 7.34 (d, J = 8.3 Hz, 1H), 6.84
■
(
s, 1H), 5.65 (s, 1H), 4.12 (q, J = 6.8 Hz, 2H), 2.55 (s, 3H),
(1) (a) Itokawa, H.; Mihara, K.; Takeya, K. Chem. Pharm. Bull. 1983,
31, 2353. (b) Kawasaki, Y.; Goda, Y.; Yoshihira, K. Chem. Pharm. Bull.
992, 40, 1504. (c) Ho, L.-K.; Don, M.-J.; Chen, H.-C.; Yeh, S.-F.;
3
2
.49 (s, 3H), 1.35 (t, J = 6.9 Hz, 3H); 1 C NMR (151 MHz,
1
CDCl ) δ 154.2, 148.6, 137.7, 132.5, 132.4, 130.8, 129.9, 129.7,
3
Chen, J.-M. J. Nat. Prod. 1996, 59, 330.
1
29.1, 126.2, 121.4, 120.0, 114.8, 99.0, 63.8, 21.7, 21.4, 14.6; IR
−1
(2) (a) Itokawa, H.; Ibraheim, Z. Z.; Qiao, Y.-F.; Takeya, K. Chem.
Pharm. Bull. 1993, 41, 1869. (b) Lumb, J.-P.; Choong, K. C.; Trauner,
D. J. Am. Chem. Soc. 2008, 130, 9230.
3) (a) Meyers, A. I.; Willemsen, J. J. Tetrahedron 1998, 54, 10493.
(b) Boonsri, S.; Karalai, C.; Ponglimanont, C.; Chantrapromma, S.;
Kanjana-opas, A. J. Nat. Prod. 2008, 71, 1173.
(
(
KBr) 3527, 3021, 1594, 1573, 1511, 1458, 1167 cm ; HRMS
ESI) calcd for C H O (M + H) 293.1542, found 293.1535.
+
20
21
2
Compound 4o. White solid, 61 mg, 70% yield, mp: 95−98
(
1
°
C; H NMR (600 MHz, CDCl ) δ 8.52 (s, 1H), 7.80 (d, J =
8
3
.6 Hz, 1H), 7.64 (dd, J = 8.6, 1.7 Hz, 1H), 7.39 (d, J = 7.9 Hz,
H), 7.35 (d, J = 8.0 Hz, 2H), 6.88 (s, 1H), 5.78 (s, 1H), 4.16
2
(
(4) Rinehart, K. L., Jr. Acc. Chem. Res. 1972, 5, 57.
13
q, J = 7.0 Hz, 2H), 2.49 (s, 3H), 1.37 (t, J = 7.0 Hz, 3H); C
(5) For selected reports since 2013, see: (a) Peng, S.; Wang, L.;
Wang, J. Chem. - Eur. J. 2013, 19, 13322. (b) He, Y.; Zhang, X.; Shen,
N.; Fan, X. J. Org. Chem. 2013, 78, 10178. (c) Jiang, H.; Cheng, Y.;
Zhang, Y.; Yu, S. Org. Lett. 2013, 15, 4884. (d) Xia, Y.; Qu, P.; Liu, Z.;
Ge, R.; Xiao, Q.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2013, 52,
2543. (e) Hammann, J. M.; Unzner, T. A.; Magauer, T. Chem. - Eur. J.
NMR (151 MHz, CDCl ) δ 156.7, 149.9, 138.3, 135.7, 130.6,
3
1
30.1, 128.8, 127.0, 124.7 (q, J = 271.7 Hz), 124.6 (q, J = 32.3
Hz), 122.5 (q, J = 3.1 Hz), 120.7 (q, J = 4.6 Hz), 118.8, 115.8,
9
1
8.8, 64.0, 21.4, 14.5; IR (KBr) 3525, 3024, 1611, 1578, 1519,
−1
463, 1176 cm ; HRMS (ESI) calcd for C H F NaO (M +
2
0
17
3
2
2
(
014, 20, 6733. (f) Kim, H. Y.; Oh, K. Org. Lett. 2014, 16, 5934.
g) Chen, Y.; Wang, L.; Sun, N.; Xie, X.; Zhou, X.; Chen, H.; Li, Y.;
+
Na) 369.1078, found 369.1070.
Compound 4p. White solid, 55 mg, 71% yield, mp: 107−
Liu, Y. Chem. - Eur. J. 2014, 20, 12015 and references therein..
(6) (a) Danheiser, R. L.; Gee, S. K. J. Org. Chem. 1984, 49, 1672.
(b) Danheiser, R. L.; Brisbois, R. G.; Kowalczyk, J. J.; Miller, R. F. J.
Am. Chem. Soc. 1990, 112, 3093. (c) Mak, X. Y.; Crombie, A. L.;
Danheiser, R. L. J. Org. Chem. 2011, 76, 1852. (d) Willumstad, T. P.;
Haze, O.; Mak, X. Y.; Lam, T. Y.; Wang, Y.-P.; Danheiser, R. L. J. Org.
Chem. 2013, 78, 11450. (e) Lam, T. Y.; Wang, Y.-P.; Danheiser, R. L. J.
Org. Chem. 2013, 78, 9396.
1
1
1
6
4
10 °C; H NMR (600 MHz, CDCl ) δ 7.78 (d, J = 8.4 Hz,
3
H), 7.40−7.36 (m, 4H), 7.32−7.28 (m, 1H), 7.26 (s, 1H),
.87 (d, J = 7.6 Hz, 1H), 5.65 (s, 1H), 4.16 (q, J = 7.0 Hz, 2H),
.04 (s, 3H), 2.47 (s, 3H), 1.35 (t, J = 7.0 Hz, 3H); 13C NMR
(
151 MHz, CDCl ) δ 154.6, 154.2, 149.1, 137.8, 130.8, 129.9,
3
1
2
29.6, 126.1, 122.8, 120.8, 115.2, 114.7, 104.9, 93.5, 63.9, 55.5,
1.4, 14.6; IR (KBr) 3525, 3051, 1598, 1584, 1497, 1449, 1122
−1
+
(7) (a) Xu, S. L.; Moore, H. W. J. Org. Chem. 1989, 54, 4024.
cm ; HRMS (ESI) calcd for C H O (M + H) 309.1491,
2
0
21
3
(
b) Turnbull, P.; Moore, H. W. J. Org. Chem. 1995, 60, 644.
8) Bao, J.; Wulff, W. D.; Fumo, M. J.; Grant, E. B.; Heller, D. P.;
Whitcomb, M. C.; Yeung, S.-M. J. Am. Chem. Soc. 1996, 118, 2166.
9) (a) Kowalski, C. J.; Lal, G. S. J. Am. Chem. Soc. 1988, 110, 3693.
(b) Koo, S.; Liebeskind, L. S. J. Am. Chem. Soc. 1995, 117, 3389.
(10) (a) Danheiser, R. L.; Helgason, A. L. J. Am. Chem. Soc. 1994,
116, 9471. (b) Danheiser, R. L.; Casebier, D. S.; Firooznia, F. J. Org.
Chem. 1995, 60, 8341. (c) Dudley, G. B.; Takaki, K. S.; Cha, D. D.;
Danheiser, R. L. Org. Lett. 2000, 2, 3407. (d) Smith, A. B., III; Adams,
C. M.; Kozmin, S. A.; Paone, D. V. J. Am. Chem. Soc. 2001, 123, 5925.
found 309.1482.
(
Compound 5a. It was prepared from 1a and 2a at 60 °C for
1
1
2
3
1
0 h to give 71 mg of 5a (87% yield) as a white solid, mp: 175−
(
1
78 °C; H NMR (600 MHz, CDCl ) δ 7.50 (d, J = 7.1 Hz,
3
H), 7.45−7.34 (m, 8H), 5.15 (s, 1H), 3.33 (s, 3H), 2.25 (s,
H); 13C NMR (151 MHz, CDCl ) δ 185.0, 160.3, 135.3,
3
29.1, 129.1, 128.6, 128.5, 128.4, 128.2, 67.2, 39.2, 37.6; IR
−1
(
KBr) 3021, 1687, 1614, 1599, 1493, 1453, 1316, 1132 cm ;
+
HRMS (ESI) calcd for C H NNaO S (M + Na) 350.0827,
1
8
17
3
(
(
11) Zhang, W.; Ready, J. M. Angew. Chem., Int. Ed. 2014, 53, 8980.
12) For the synthesis of aryl tert-butyl ynol ethers, see: (a) Marzo,
found 350.0821.
Compound 5b. Colorless oil, 60 mg, 82% yield; H NMR
17b
1
L.; Parra, A.; Frías, M.; Aleman
2013, 2013, 4405. For the synthesis of other ynol ethers, see:
b) Jouvin, K.; Bayle, A.; Legrand, F.; Evano, G. Org. Lett. 2012, 14,
652. (c) Tanaka, R.; Miller, S. I. Tetrahedron Lett. 1971, 12, 1753.
(d) Moyano, A.; Charbonnier, F.; Greene, A. E. J. Org. Chem. 1987, 52,
919.
13) For selected reports on ynol ethers since 2014, see: (a) Ding, S.;
́
, J.; Ruano, J. L. G. Eur. J. Org. Chem.
(
4
600 MHz, CDCl ) δ 7.88−7.83 (m, 2H), 7.39−7.26 (m, 8H),
3
.82 (s, 1H), 1.38 (s, 9H).
(
1
ASSOCIATED CONTENT
■
2
(
* Supporting Information
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b01858.
Jia, G.; Sun, J. Angew. Chem., Int. Ed. 2014, 53, 1877. (b) Arai, S.;
Nakajima, M.; Nishida, A. Angew. Chem., Int. Ed. 2014, 53, 5569.
(
2
2
c) D’Oyley, J. M.; Aliev, A. E.; Sheppard, T. D. Angew. Chem., Int. Ed.
014, 53, 10747. (d) Alford, J. S.; Davies, H. M. L. J. Am. Chem. Soc.
014, 136, 10266. (e) Puri, S.; Thirupathi, N.; Reddy, M. S. Org. Lett.
Spectroscopic data of products 3 and 4 (PDF)
X-ray data of 3v (CIF)
X-ray data of 4a (CIF)
2014, 16, 5246. (f) Babu, M. H.; Dwivedi, V.; Kant, R.; Reddy, M. S.
G
DOI: 10.1021/acs.joc.5b01858
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Angew. Chem., Int. Ed. 2015, 54, 3783. (g) Fabig, S.; Haberhauer, G.;
Gleiter, R. J. Am. Chem. Soc. 2015, 137, 1833. (h) Saito, N.; Sun, Z.;
Sato, Y. Chem. - Asian J. 2015, 10, 1170. (i) Minami, Y.; Kanda, M.;
Sakai, M.; Hiyama, T. Tetrahedron 2015, 71, 4522.
(
14) For our recent works on ynol ethers, see: (a) Cai, H.; Yuan, Z.;
Zhu, W.; Zhu, G. Chem. Commun. 2011, 47, 8682. (b) Bai, Y.; Yin, J.;
Kong, W.; Mao, M.; Zhu, G. Chem. Commun. 2013, 49, 7650. (c) Cui,
W.; Mao, M.; He, Z.; Zhu, G. J. Org. Chem. 2013, 78, 9815. (d) Cui,
W.; Ying, J.; Zheng, R.; Cheng, C.; Bai, Y.; Zhu, G. J. Org. Chem. 2014,
79, 3487. (e) Yin, J.; Bai, Y.; Mao, M.; Zhu, G. J. Org. Chem. 2014, 79,
9179.
(
15) For selected reviews on ynamides, see: (a) DeKorver, K. A.; Li,
H.; Lohse, A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem.
Rev. 2010, 110, 5064. (b) Evano, G.; Gaumont, A.-C.; Alayrac, C.;
Wrona, I. E.; Giguere, J. R.; Delacroix, O.; Bayle, A.; Jouvin, K.;
Theunissen, C.; Gatignol, J.; Silvanus, A. C. Tetrahedron 2014, 70,
1529. For our recent works on ynamides, see: (c) Liu, G.; Kong, W.;
Che, J.; Zhu, G. Adv. Synth. Catal. 2014, 356, 3314. (d) Yang, Y.;
Wang, L.; Zhang, F.; Zhu, G. J. Org. Chem. 2014, 79, 9319. (e) Yang,
Y.; Wang, L.; Zhang, J.; Jin, Y.; Zhu, G. Chem. Commun. 2014, 50,
2347. (f) Cheng, C.; Liu, S.; Zhu, G. Org. Lett. 2015, 17, 1581.
(
16) CCDC 1412471 (3v) and 1412472 (4a) contain the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from the Cambridge Crystallographic Data
Center via www.ccdc.cam.ac.uk/data_request/cif.
(
̀
17) (a) Valentí, E.; Pericas, M. A.; Serratosa, F. J. Org. Chem. 1990,
55, 395. (b) Gray, V. J.; Slater, B.; Wilden, J. D. Chem. - Eur. J. 2012,
8, 15582. (c) Tran, V.; Minehan, T. G. Org. Lett. 2011, 13, 6588.
1
H
DOI: 10.1021/acs.joc.5b01858
J. Org. Chem. XXXX, XXX, XXX−XXX