Preparation of (Z)-α,β-disubstituted enamides via palladium-catalyzed addition of boronic acids to ynamides

Article abstract of DOI:10.1021/jo501894j

A Pd-catalyzed, highly regio- and stereoselective addition of boronic acids to ynamides has been realized. This protocol generates (Z)-α,β-disubstituted enamides in high yields with excellent regio- and stereoselectivity under the mild reaction conditions, thereby providing a good complementary method for the diverse synthesis of multifunctional enamides. A wide collection of functional groups are found to be tolerated. It represents a straightforward and useful means to assemble stereodefined enamides from readily available starting materials.

Full text of DOI:10.1021/jo501894j

Article
pubs.acs.org/joc
Preparation of (Z)‑α,β-Disubstituted Enamides via Palladium-
Catalyzed Addition of Boronic Acids to Ynamides
Yuanfa Yang, Lina Wang, Fang Zhang, and Gangguo Zhu*
Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China
S
* Supporting Information
ABSTRACT: A Pd-catalyzed, highly regio- and stereoselective addition of
boronic acids to ynamides has been realized. This protocol generates (Z)-α,β-
disubstituted enamides in high yields with excellent regio- and stereoselectivity
under the mild reaction conditions, thereby providing a good complementary
method for the diverse synthesis of multifunctional enamides. A wide collection
of functional groups are found to be tolerated. It represents a straightforward
and useful means to assemble stereodefined enamides from readily available starting materials.
accomplished a Pd-catalyzed trans-addition of boronic acids to
N-sulfonyl ynamides, giving (E)-α,β-disubstituted enamides
regio- and stereoselectively under the mild conditions.10 In
contrast, the coupling of boronic acids with ynamides affording
stereodefined (Z)-α,β-disubstituted enamides is still unrevealed.
In this report, a Pd-catalyzed stereospecific addition of boronic
acids10−12 to ynamides leading to (Z)-α,β-disubstituted
enamides has been achieved. Clearly, it can offer a good
complementary method to previous interest7,10 in the assembly
of multisubstituted enamides with high scaffold diversity.
INTRODUCTION
■
Enamides are versatile building blocks that can be utilized in the
heterocycle construction, asymmetric hydrogenation, and syn-
thesis of bioactive molecules, such as salicylihalamides,
lobatamides, oximidines, and others.1 Accordingly, a myriad of
efforts have been devoted to the generation of this framework.
Despite the impressive advances in this field, it is still highly
desirable to develop simple as well as effective methods for the
regio- and stereoselective preparation of enamides, particularly
the thermodynamically unfavorable Z-isomers. Recently, the
functionalization of ynamides, mainly featured by hydro-
metalation, carbometalation, or heterometalation processes,
has emerged as an appealing strategy to construct enamides.2−6
In particular, by taking advantage of the coordination
interaction between oxygen and rhodium atoms, Lam and co-
workers successfully achieved an elegant Rh-catalyzed addition
of boronic acids to ynamides that produced β,β′-disubstituted
enamides in good to excellent regioselectivity (rr ≥ 6:1)
(Scheme 1).7,8 Recent studies in our laboratory have focused on
the transformation of ynamides,9,10 and as an example, we have
RESULTS AND DISCCUSION
■
Initial studies to optimize the reaction conditions were
performed with ynamide 1a and PhB(OH)2 (2a) as the test
substrates. Pleasantly, when the reaction was conducted with 5
mol % of Pd(OAc)2, 10 mol % of PPh3, and 1.5 equiv of Na2CO3
in dioxane under a nitrogen atmosphere at 70 °C for 4 h, 3aa
was isolated in 80% yield (Table 1, entry 1). Other bases,
including Cs2CO3, K3PO4, KF, and CsF, resulted in low yield or
poor regioselectivity (Table 1, entries 3−6). In addition,
switching dioxane to other solvents, such as THF, DMF, and
toluene, just led to the inferior results (Table 1, entries 8−10).
Then, we examined the ligand for this reaction. Generally,
variation of ligands did not affect the regioselectivity of addition;
however, it did have a significant impact on the reaction
efficiency (Table 1, entries 11−17), and specifically, the
utilization of P(3-tol)3 as the ligand afforded the highest
efficiency, giving 3aa in 90% yield with excellent regio- and
stereoselectivity. Of note, the reaction could be carried out
under an atmosphere of air, nevertheless with somewhat lower
yield (Table 1, entry 18). As such, the best reaction conditions
found for Pd-catalyzed addition of boronic acids to ynamides
consisted of 5 mol % of Pd(OAc)2, 10 mol % of P(3-tol)3, 1.5
equiv of boronic acids, and 1.5 equiv of Na2CO3 in dioxane at 70
°C for 4 h.
Scheme 1. Summary of Addition of Boronic Acids to
Ynamides
Received: August 17, 2014
© XXXX American Chemical Society
A
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a
a
Table 1. Optimization of the Reaction Conditions
Table 2. Scope of Boronic Acids
b
c
b
entry
base
ligand
solvent
3aa/3aa′ yield (%)
entry
R (2)
yield (%)
1
2
3
4
5
6
7
Na2CO3
K2CO3
Cs2CO3
K3PO4
KF
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
THF
>20:1
>20:1
>20:1
>20:1
>20:1
2:1
80
69
18
34
32
71
63
87
25
65
86
90
85
87
78
62
31
76
1
2
Ph (2a)
89 (3ba)
93 (3bb)
91 (3bc)
72 (3bd)
76 (3be)
70 (3bf)
65 (3bg)
76 (3bh)
86 (3bi)
83 (3bj)
90 (3bk)
92 (3bl)
83 (3bm)
87 (3bn)
91 (3bo)
78 (3bp)
76 (3bq)
84 (3br)
86 (3bs)
72 (3bt)
4-F-C6H4 (2b)
3
2,4-F2-C6H3 (2c)
3-NO2-C6H4 (2d)
4-Ac-C6H4 (2e)
4-CN-C6H4 (2f)
4-CHO-C6H4 (2g)
4-Cl-C6H4 (2h)
4-Me-C6H4 (2i)
3-Me-C6H4 (2j)
2-Me-C6H4 (2k)
4-MeO-C6H4 (2l)
4
5
CsF
6
1.5:1
7
d
8
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
6:1
8
d
9
d
DMF
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
9
10
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
10
11
12
13
14
15
16
17
18
19
20
11
12
13
14
15
16
17
P(2-tol)3
P(3-tol)3
P(4-tol)3
P(2-furyl)3
P(4-OMeC6H4)3
PCy3
3,4-(OMe)2-C6H3 (2m)
3,4-methylenedioxyphenyl (2n)
2-naphthyl (2o)
2-furyl (2p)
dppb
2-thienyl (2q)
e
18
P(3-tol)3
(E)-styryl (2r)
a
(E)-1-pentenyl (2s)
PhCCBF3K (2t)
Reaction conditions: 1a (0.3 mmol), 2a (0.45 mmol), Pd(OAc)2 (5
mol %), ligand (10 mol %), base (1.5 equiv), and solvent (1.5 mL) at
70 °C for 4 h. Determined by GC. Isolated yield. 6 h. Under air
b
c
d
e
a
Reaction conditions: 1b (0.3 mmol), 2 (0.45 mmol), Pd(OAc)2 (5
mol %), P(3-tol)3 (10 mol %), Na2CO3 (1.5 equiv), and dioxane (1.5
mL) at 70 °C. Isolated yield.
atmosphere.
b
ab c
, ,
After the optimized reaction conditions had been established,
the scope of this reaction was investigated using a panel of
organoboron reagents (Table 2). Various boronic acids bearing
either electron-donating or electron-withdrawing groups in the
aryl ring of 2 turned out to be the effective reacting partners,
delivering the desired (Z)-α,β-disubstituted enamides 3ba−bn
in good to excellent yields with perfect control of regio- and
stereoselectivity (Table 2, entries 1−14). Notably, the steric
hindrance of 2 seemed to have no detrimental effect on the
reaction yield, as demonstrated by the transformation of 4-, 3-,
and 2-tolylboronic acids 2i−k (Table 2, entries 9−11). Further,
the reaction was applicable to heteroarylboronic acids. For
example, the coupling of 2-furylboronic acid (2p) and 2-
thienylboronic acid (2q) proceeded efficiently to form the
corresponding products in satisfactory yields (Table 2, entries
16 and 17). In addition to aryl boronic acids, alkenyl boronic
acids 2r and 2s were also competent substrates, leading to 3br
and 3bs in 84% and 86% yield, respectively (Table 2, entries 18
and 19). Lastly, the reaction of potassium phenylethynyltri-
fluoroborate (2t) took place smoothly to deliver 3bt in
outstanding regio- and stereoselectivity (Table 2, entry 20). In
contrast, MeB(OH)2 (2u) was not applicable to this reaction
owing to the formation of some complicated byproducts. The
single-crystal X-ray diffraction analysis of enamide 3bm
confirmed the regio- and stereochemistry of this Pd-catalyzed
addition reaction (see the Supporting Information).
Table 3. Scope of Substrates 1
a
Reaction conditions: 1 (0.3 mmol), 2 (0.45 mmol), Pd(OAc)2 (5
mol %), P(3-tol)3 (10 mol %), Na2CO3 (1.5 equiv), and dioxane (1.5
mL) at 70 °C for 4−7 h. Isolated yield. rr > 10:1, determined by GC.
b
c
imidazole-substituted substrates 1j and 1k, for example, could
also be utilized as the coupling partners without incident (Table
3, 3ja and 3ks). Additionally, ynamine 1m, an indole-derived
substrate, was successfully transformed into (Z)-α,β-disubsti-
tuted enamine 3mi13 in 87% isolated yield (Table 3, 3mi).
Likewise, 1-(phenylethynyl)pyrrolidin-2-one (1o) reacted
efficiently with 2a to give 3oa14 in high yield, and no erosion
of regioselectivity was observed (Table 3, 3oa).15
On the other hand, this transformation covers a broad range
of ynamides (Table 3). Oxazolidinone-substituted ynamides,
including electron-poor and electron-rich ones 1c−1h, all
furnished the desired hydrophenylation products in high yields
(Table 3, 3ca−3ha). Alkyl ynamide 1i also underwent the facile
coupling to form 3ia in excellent yield and regioselectivity
(Table 3, 3ia). Remarkably, besides ynamides, ynamines,
B
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Scheme 2. Possible Mechanism
Meanwhile, ynamide 1i was treated with 0.5 equiv of
(PhBO)3 and 5 equiv of D2O under the standard reaction
conditions, which resulted in the formation of 3ia-d in 87% yield
that this protocol offers a simple, direct, and highly useful means
to access (Z)-α,β-disubstituted enamides from the readily
accessible starting materials.
16
with 85% deuterium incorporation (eq 1). According to the
EXPERIMENTAL SECTION
■
General. Melting points were measured by a melting point
instrument and were uncorrected. Unless otherwise noted, purchased
chemicals were used directly from commercial suppliers without further
1
purification. H, 13C, and 19F NMR spectra were measured on 400 or
600 MHz NMR spectrometers using CDCl3 as the solvent with
tetramethylsilane (TMS) as the internal standard. Chemical shifts were
given in δ relative to TMS, and the coupling constants were given in
Hz. High-resolution mass spectra (HRMS) analyses were carried out
using a TOF MS instrument with an ESI source. Column
chromatography was performed with silica gel (300−400 mesh)
using petroleum ether/EtOAc as the eluent.
above results and previous reports,10,11 a possible mechanism is
proposed in Scheme 2 for this Pd-catalyzed regio- and
stereoselective addition of boronic acids to ynamides and
related compounds. A palladium intermediate I, generated by
the oxidative addition of Pd(0) with 2,11d,17 undergoes the
carbopalladation of 1 to form the species II regio- and
stereoselectively. Then, the hydrolysis of the Pd−B bond of II
and subsequent reductive elimination produces 3 and closes the
catalytic cycle (Scheme 2, path a). However, another possibility
cannot be ruled out at the current stage, which may involve the
following steps: (1) generation of IV via transmetalation of
Pd(II) complexes with boronic acids; (2) carbopalladation of 1
with IV, yielding an alkenyl palladium species V; and (3)
protonolysis of the alkenyl C−Pd bond18 of V, finally delivering
3 with reproduction of the Pd(II) catalyst (Scheme 2, path b).
To demonstrate the synthetic utility of this transformation,
1,3-dienamide 3br was treated with 1.2 equiv of diethyl
acetylenedicarboxylate (4) in toluene at reflux for 16 h; as a
result, it produced the 1,4-cyclohexadiene derivative 5 in 67%
yield upon isolation (eq 2).19
General Procedure for Pd-Catalyzed Addition of Boronic
Acids to Ynamides. To a mixture of P(3-tol)3 (9.1 mg, 0.03 mmol),
Pd(OAc)2 (3.4 mg, 0.015 mmol), Na2CO3 (47.7 mg, 0.45 mmol), and
2a (54.9 mg, 0.45 mmol) in 1.5 mL of 1,4-dioxane was added 1a (60.3
mg, 0.3 mmol) under a N2 atmosphere. After stirring at 70 °C for 4 h,
the reaction mixture was quenched with 5 mL of water, extracted with
EtOAc, washed with brine, dried over anhydrous Na2SO4, and
concentrated. Column chromatography on silica gel (petroleum
ether/EtOAc = 2:1) gave 75 mg of 3aa as a white solid, 90% yield,
mp 112−114 °C; 1H NMR (CDCl3, 600 MHz) δ 2.40 (s, 3 H), 3.72 (t,
J = 7.9 Hz, 2 H), 4.47 (t, J = 8.6 Hz, 2 H), 6.87 (s, 1 H), 7.22 (d, J = 8.0
Hz, 2 H), 7.35−7.39 (m, 3 H), 7.41−7.44 (m, 2 H), 7.49−7.50 (m, 2
H); 13C NMR (CDCl3, 150 MHz) δ 21.2, 45.2, 62.5, 125.7, 126.9,
128.2, 128.6, 128.7, 129.4, 132.3, 133.6, 136.4, 138.1, 156.3; MS (EI, m/
z): 280 (23), 279 (M+, 100), 234 (21), 220 (42), 192 (92); HRMS
(ESI) calcd for C18H17NO2 (M+) 279.1259, found 279.1266.
Compound 3ba.20 71 mg, 89% yield, white solid, mp 103−105 °C;
1H NMR (CDCl3, 600 MHz) δ 3.67 (t, J = 7.9 Hz, 2 H), 4.43 (t, J = 8.1
Hz, 2 H), 6.87 (s, 1 H), 7.29−7.33 (m, 1 H), 7.36−7.44 (m, 7 H),
7.46−7.49 (m, 2 H); 13C NMR (CDCl3, 150 MHz) δ 45.2, 62.4, 125.7,
125.7, 126.8, 128.0, 128.1, 128.6, 128.7, 134.4, 135.1, 136.2, 156.2.
Compound 3bb. 79 mg, 93% yield, white solid, mp 129−131 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.66 (t, J = 7.9 Hz, 2 H), 4.43 (t, J = 8.2 Hz,
2 H), 6.79 (s, 1 H), 7.05−7.12 (m, 2 H), 7.30−7.31 (m, 1 H), 7.37−
7.46 (m, 6 H); 13C NMR (CDCl3, 150 MHz) δ 45.2, 62.5, 115.7 (d, J =
21.9 Hz), 126.5, 127.7 (d, J = 8.3 Hz), 128.1, 128.2, 128.7, 132.6 (d, J =
3.2 Hz), 133.6, 135.0, 156.2, 162.9 (d, J = 248.8 Hz); 19F NMR
(CDCl3, 565 MHz): δ −112.5; MS (EI, m/z): 284 (15), 283 (M+, 82),
238 (19), 224 (34), 196 (100); HRMS (ESI) calcd for C17H14FNO2
(M+) 283.1009, found 283.1016.
CONCLUSION
■
In summary, a highly regio- and stereoselective addition of
boronic acids to ynamides has been accomplished with the
readily available Pd(OAc)2/P(3-tol)3 catalytic system. The
reaction produces (Z)-α,β-disubstituted enamides and related
compounds in high yields with excellent regio- and stereo-
selectivity under mild reaction conditions, thereby providing a
good complementary method for the diverse synthesis of highly
substituted enamides. A broad spectrum of functional groups,
such as F, Cl, NO2, Ac, CHO, CN, OMe, furyl, thienyl, alkenyl,
and alkynyl substituents, are well tolerated. Overall, we believe
Compound 3bc. 82 mg, 91% yield, white solid, mp 137−139 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.63 (t, J = 7.9 Hz, 2 H), 4.36 (t, J = 7.9 Hz,
2 H), 6.57 (s, 1 H), 6.83 (td, J = 2.3, 8.8 Hz, 1 H), 6.92 (td, J = 1.7, 8.2
Hz, 1 H), 7.29−7.32 (m, 1 H), 7.35−7.50 (m, 5 H); 13C NMR (CDCl3,
150 MHz) δ 44.8, 62.7, 104.2 (t, J = 26.1 Hz), 111.7 (dd, J = 5.6, 21.2
Hz), 121.3 (dd, J = 4.0, 11.9 Hz), 128.2, 128.4, 128.7, 129.1, 131.2 (dd,
J = 4.8, 9.7 Hz), 134.7, 156.3, 160.0 (dd, J = 12.5, 251.0 Hz), 163.0 (dd,
C
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J = 12.3, 261.0 Hz); 19F NMR (CDCl3, 565 MHz): δ −108.9 (d, J = 8.7
Hz), −112.9 (d, J = 8.5 Hz); MS (EI, m/z): 302 (16), 301 (M+, 93),
256 (22), 242 (59), 214 (100); HRMS (ESI) calcd for C17H13F2NO2
(M+) 301.0914, found 301.0919.
(m, 1 H), 7.37−7.43 (m, 6 H); 13C NMR (CDCl3, 150 MHz) δ 45.2,
55.2, 62.4, 114.1, 124.8, 127.1, 127.7, 128.0, 128.5, 128.6, 134.0, 135.3,
156.2, 160.0; MS (EI, m/z): 296 (8), 295 (M+, 100), 250 (9), 208 (86),
193 (28); HRMS (ESI) calcd for C18H17NO3 (M+) 295.1208, found
295.1217.
Compound 3bm. 81 mg, 83% yield, white solid, mp 142−144 °C;
1H NMR (CDCl3, 600 MHz) δ 3.67 (t, J = 8.1 Hz, 2 H), 3.89 (s, 3 H),
3.91 (s, 3 H), 4.42 (t, J = 8.0 Hz, 2 H), 6.77 (s, 1 H), 6.86−6.90 (m, 1
H), 7.00−7.01 (m, 2 H), 7.26−7.29 (m, 1 H), 7.35−7.37 (m, 2 H), 7.41
(d, J = 7.7 Hz, 2 H); 13C NMR (CDCl3, 150 MHz) δ 45.3, 55.7, 55.8,
62.3, 109.0, 111.0, 118.5, 125.1, 127.7, 127.9, 128.5, 129.0, 134.2, 135.2,
149.0, 149.6, 156.1; MS (EI, m/z): 326 (18), 325 (M+, 100), 309 (11),
238 (39), 223 (16); HRMS (ESI) calcd for C19H19NO4 (M+) 325.1314,
found 325.1326.
Crystal data for 3bm (C19H19NO4, 325.35): monoclinic, space group
P2(1)/c, a = 12.4071(7) Å, b = 12.8438(7) Å, c = 11.3777(6) Å, U =
1632.86(15) Å3, Z = 4, T = 296(2) K, absorption coefficient 0.093
mm−1, reflections collected 25 322, independent reflections 3784
[R(int) = 0.0398], refinement by full-matrix least-squares on F2, data/
restraints/parameters 3784/0/217, goodness-of-fit on F2 = 1.055, final
R indices [I > 2σ(I)] R1 = 0.0439, wR2 = 0.1199, R indices (all data) R1
= 0.0631, wR2 = 0.1322, largest diff peak and hole 0.188 and −0.165 e·
Å−3. Crystallographic data for the structure 3bm have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 1018715.
Compound 3bd. 67 mg, 72% yield, white solid, mp 136−138 °C; 1H
NMR (CDCl3, 400 MHz) δ 3.70 (t, J = 7.9 Hz, 2 H), 4.48 (t, J = 8.2 Hz,
2 H), 6.94 (s, 1 H), 7.33−7.44 (m, 5 H), 7.53−7.61 (m, 1 H), 7.77−
7.79 (m, 1 H), 8.17−8.19 (m, 1 H), 8.30−8.31 (m, 1 H); 13C NMR
(CDCl3, 100 MHz) δ 45.0, 62.8, 120.6, 123.3, 128.4, 128.7, 128.8,
128.9, 129.8, 131.6, 132.6, 134.3, 138.6, 148.6, 156.2; MS (EI, m/z):
311 (15), 310 (M+, 100), 280 (11), 265 (11), 251 (19); HRMS (ESI)
calcd for C17H14N2O4 (M+) 310.0954, found 310.0965.
Compound 3be. 70 mg, 76% yield, white solid, mp 141−143 °C; 1H
NMR (CDCl3, 600 MHz) δ 2.61 (s, 3 H), 3.67−3.70 (m, 2 H), 4.47 (t,
J = 8.2 Hz, 2 H), 6.96 (s, 1 H), 7.32−7.34 (m, 1 H), 7.39−7.41 (m, 2
H), 7.43−7.45 (m, 2 H), 7.55 (d, J = 8.5 Hz, 2 H), 7.98 (d, J = 8.4 Hz, 2
H); 13C NMR (CDCl3, 150 MHz) δ 26.6, 45.2, 62.6, 125.9, 128.4,
128.6, 128.8, 128.9, 129.0, 133.7, 134.7, 137.0, 141.0, 156.3, 197.3; MS
(EI, m/z): 308 (11), 307 (M+, 59), 281 (29), 248 (10), 220 (20);
HRMS (ESI) calcd for C19H17NO3 (M+) 307.1208, found 307.1216.
Compound 3bf. 61 mg, 70% yield, white solid, mp 135−137 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.66 (t, J = 8.2 Hz, 2 H), 4.46 (t, J = 8.1 Hz,
2 H), 6.94 (s, 1 H), 7.34−7.35 (m, 1 H), 7.39−7.43 (m, 4 H), 7.56 (d, J
= 8.3 Hz, 2 H), 7.66−7.67 (m, 2 H); 13C NMR (CDCl3, 150 MHz) δ
45.0, 62.7, 112.0, 118.5, 126.3, 128.4, 128.4, 128.9, 129.4, 129.6, 132.5,
134.3, 141.1, 156.2; MS (EI, m/z): 291 (7), 290 (M+, 40), 281 (27),
245 (13), 231 (26); HRMS (ESI) calcd for C18H14N2O2 (M+)
290.1055, found 290.1063.
Compound 3bn. 81 mg, 87% yield, white solid, mp 157−159 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.65 (t, J = 8.0 Hz, 2 H), 4.40 (t, J = 8.3 Hz,
2 H), 5.97 (s, 2 H), 6.72 (s, 1 H), 6.81 (d, J = 8.0 Hz, 1 H), 6.92−6.97
(m, 2 H), 7.27−7.31 (m, 1 H), 7.36−7.38 (m, 4 H); 13C NMR (CDCl3,
150 MHz) δ 45.2, 62.4, 101.3, 106.1, 108.3, 119.8, 125.3, 127.8, 128.0,
128.6, 130.6, 134.1, 135.1, 148.1, 148.1, 156.1; MS (EI, m/z): 310 (19),
309 (M+, 100), 222 (87), 223 (18), 207 (11); HRMS (ESI) calcd for
C18H15NO4 (M+) 309.1001, found 309.1009.
Compound 3bg. 57 mg, 65% yield, white solid, mp 131−133 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.69 (t, J = 8.2 Hz, 2 H), 4.47 (t, J = 8.5 Hz,
2 H), 6.98 (s, 1 H), 7.33−7.34 (m, 1 H), 7.38−7.42 (m, 2 H), 7.44 (d, J
= 7.2 Hz, 2 H), 7.62 (d, J = 8.2 Hz, 2 H), 7.89−7.90 (m, 2 H), 10.0 (s, 1
H); 13C NMR (CDCl3, 150 MHz) δ 45.1, 62.6, 126.3, 128.4, 128.7,
128.8, 129.3, 130.1, 133.5, 134.5, 136.2, 142.4, 156.3, 191.4; MS (EI, m/
z): 294 (12), 293 (M+, 69), 281 (27), 248 (10), 234 (16); HRMS (ESI)
calcd for C18H15NO3 (M+) 293.1052, found 293.1059.
Compound 3bo. 86 mg, 91% yield, white solid, mp 164−166 °C; 1H
NMR (CDCl3, 400 MHz) δ 3.70 (t, J = 7.9 Hz, 2 H), 4.45 (t, J = 8.4 Hz,
2 H), 7.00 (s, 1 H), 7.33−7.34 (m, 1 H), 7.42 (d, J = 7.6 Hz, 2 H),
7.48−7.52 (m, 4 H), 7.58−7.61 (m, 1 H), 7.86−7.88 (m, 3 H), 7.92 (s,
1 H); 13C NMR (CDCl3, 100 MHz) δ 45.2, 62.5, 123.4, 125.0, 126.4,
127.2, 127.5, 128.0, 128.2, 128.3, 128.5, 128.6, 133.2, 133.3, 133.6,
134.3, 135.1, 156.3; MS (EI, m/z): 316 (17), 315 (M+, 90), 270 (12),
256 (11), 228 (100); HRMS (ESI) calcd for C21H17NO2 (M+)
315.1259, found 315.1267.
Compound 3bh. 68 mg, 76% yield, white solid, mp 136−138 °C; 1H
NMR (CDCl3, 400 MHz) δ 3.68 (t, J = 7.8 Hz, 2 H), 4.46 (t, J = 8.3 Hz,
2 H), 6.85 (s, 1 H), 7.39−7.43 (m, 9 H); 13C NMR (CDCl3, 100 MHz)
δ 45.1, 62.5, 127.0, 127.1, 128.2, 128.3, 128.7, 128.9, 133.5, 134.5,
134.8, 134.9, 156.2; MS (EI, m/z): 301 (30), 299 (M+, 100), 254 (17),
240 (34), 212 (91); HRMS (ESI) calcd for C17H14ClNO2 (M+)
299.0713, found 299.0725.
Compound 3bp. 60 mg, 78% yield, white solid, mp 142−144 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.72 (t, J = 8.0 Hz, 2 H), 4.47 (t, J = 8.2 Hz,
2 H), 6.47 (d, J = 3.4 Hz, 1 H), 6.47−6.48 (m, 1 H), 7.08 (s, 1 H),
7.32−7.34 (m, 1 H), 7.38−7.41 (m, 2 H), 7.46−7.47 (m, 3 H); 13C
NMR (CDCl3, 150 MHz) δ 45.2, 62.7, 107.8, 111.8, 125.1, 128.3,
128.4, 128.4, 128.7, 134.1, 143.1, 150.1, 156.7; MS (EI, m/z): 256 (12),
255 (M+, 86), 207 (22), 182 (14), 168 (100); HRMS (ESI) calcd for
C15H13NO3 (M+) 255.0895, found 255.0905.
Compound 3bi. 72 mg, 86% yield, white solid, mp 132−135 °C; 1H
NMR (CDCl3, 600 MHz) δ 2.39 (s, 3 H), 3.67 (t, J = 7.8 Hz, 2 H), 4.43
(t, J = 8.1 Hz, 2 H), 6.83 (s, 1 H), 7.22 (d, J = 8.0 Hz, 2 H), 7.28−7.30
(m, 1 H), 7.36−7.46 (m, 6 H); 13C NMR (CDCl3, 150 MHz) δ 21.1,
45.3, 63.4, 125.7, 125.9, 127.9, 128.1, 128.6, 129.4, 133.4, 134.4, 135.2,
138.8, 156.3; MS (EI, m/z): 280 (26), 279 (M+, 100), 234 (33), 220
(64), 192 (73); HRMS (ESI) calcd for C18H17NO2 (M+) 279.1259,
found 279.1263.
Compound 3bj. 69.5 mg, 83% yield, white solid, mp 135−137 °C;
1H NMR (CDCl3, 400 MHz) δ 2.42 (s, 3 H), 3.70 (t, J = 7.9 Hz, 2 H),
4.47 (t, J = 8.3 Hz, 2 H), 6.88 (s, 1 H), 7.20−7.22 (m, 1 H), 7.28−7.34
(m, 4 H), 7.39−7.47 (m, 4 H); 13C NMR (CDCl3, 100 MHz) δ 21.4,
45.3, 62.5, 123.0, 126.5, 126.7, 128.0, 128.2, 128.6, 128.7, 129.6, 134.6,
135.2, 136.3, 138.4, 156.3; MS (EI, m/z): 280 (18), 279 (M+, 100), 234
(18), 220 (38), 192 (87); HRMS (ESI) calcd for C18H17NO2 (M+)
279.1259, found 279.1267.
Compound 3bq. 62 mg, 76% yield, white solid, mp 147−149 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.71 (t, J = 8.0 Hz, 2 H), 4.43 (t, J = 8.2 Hz,
2 H), 6.94 (s, 1 H), 7.02−7.03 (m, 1 H), 7.13 (d, J = 3.5 Hz, 1 H),
7.27−7.50 (m, 6 H); 13C NMR (CDCl3, 150 MHz) δ 45.1, 62.6, 124.5,
125.7, 126.1, 127.8, 128.2, 128.2, 128.4, 128.7, 134.3, 140.9, 156.3; MS
(EI, m/z): 272 (32), 271 (M+, 84), 226 (37), 212 (52), 198 (15);
HRMS (ESI) calcd for C15H13NO2S (M+) 271.0667, found 271.0673.
Compound 3br. 73 mg, 84% yield, white solid, mp 135−137 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.67 (t, J = 7.9 Hz, 2 H), 4.47 (t, J = 7.8 Hz,
2 H), 6.63 (d, J = 15.9 Hz, 1 H), 6.73 (s, 1 H), 6.83 (d, J = 15.9 Hz, 1
H), 7.29−7.48 (m, 10 H); 13C NMR (CDCl3, 150 MHz) δ 44.8, 62.6,
125.5, 126.7, 128.0, 128.3, 128.5, 128.7, 129.3, 131.0, 133.7, 134.4,
136.1, 156.7; MS (EI, m/z): 292 (12), 291 (M+, 59), 246 (23), 230
(20), 218 (26); HRMS (ESI) calcd for C19H17NO2 (M+) 291.1259,
found 291.1267.
Compound 3bk. 75 mg, 90% yield, white solid, mp 136−138 °C; 1H
NMR (CDCl3, 600 MHz) δ 2.42 (s, 3 H), 3.60 (t, J = 8.0 Hz, 2 H), 4.38
(t, J = 8.2 Hz, 2 H), 6.43 (s, 1 H), 7.26−7.28 (m, 2 H), 7.31−7.34 (m, 2
H), 7.38−7.44 (m, 5 H); 13C NMR (CDCl3, 150 MHz) δ 20.0, 45.0,
62.1, 126.0, 127.1, 127.6, 128.1, 128.5, 128.6, 129.6, 130.6, 134.2, 135.4,
136.2, 136.8, 154.8; MS (EI, m/z): 280 (23), 279 (M+, 100), 234 (28),
220 (35), 206 (27); HRMS (ESI) calcd for C18H17NO2 (M+) 279.1259,
found 279.1265.
Compound 3bs. 66 mg, 86% yield, white solid, mp 119−121 °C; 1H
NMR (CDCl3, 600 MHz) δ 0.92 (t, J = 7.4 Hz, 3 H), 1.45−1.47 (m, 2
H), 2.13−2.17 (m, 2 H), 3.56 (t, J = 8.1 Hz, 2 H), 4.37 (t, J = 8.1 Hz, 2
H), 5.74−5.79 (m, 1 H), 6.05 (d, J = 15.6 Hz, 1 H), 6.47 (s, 1 H), 7.22−
7.25 (m, 1 H), 7.30−7.33 (m, 4 H); 13C NMR (CDCl3, 150 MHz) δ
Compound 3bl. 81 mg, 92% yield, white solid, mp 142−144 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.68 (t, J = 8.0 Hz, 2 H), 3.84 (s, 3 H), 4.43
(t, J = 8.3 Hz, 2 H), 6.78 (s, 1 H), 6.95 (d, J = 8.8 Hz, 2 H), 7.28−7.31
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Article
13.6, 22.1, 34.3, 44.9, 62.5, 126.5, 127.8, 128.0, 128.1, 128.5, 132.2,
133.5, 134.6, 156.7; MS (EI, m/z): 257 (40), 256 (M+, 26), 230 (12),
214 (83), 198 (10); HRMS (ESI) calcd for C16H19NO2 (M+) 257.1416,
found 257.1419.
1.25−1.37 (m, 10 H), 1.46−1.54 (m, 2 H), 2.21 (t, J = 7.3 Hz, 2 H),
3.65 (t, J = 8.0 Hz, 2 H), 4.46 (t, J = 8.2 Hz, 2 H), 6.01 (t, J = 7.2 Hz,
0.15 H), 7.28−7.36 (m, 5 H).
Compound 3ja. 69.5 mg, 89% yield, white solid, mp 112−114 °C;
1H NMR (CDCl3, 400 MHz) δ 2.40 (s, 3 H), 6.70 (s, 1 H), 6.96 (s, 1
H), 7.06 (d, J = 8.0 Hz, 2 H), 7.13 (s, 1 H), 7.20 (d, J = 7.9 Hz, 2 H),
7.28−7.41 (m, 6 H); 13C NMR (CDCl3, 100 MHz) δ 21.3, 119.1,
120.0, 127.6, 128.2, 128.5, 128.7, 129.5, 129.8, 134.2, 135.2, 137.6,
138.3, 140.0; MS (EI, m/z): 261 (15), 260 (M+, 69), 259 (100), 245
(28), 232 (41); HRMS (ESI) calcd for C18H16N2 (M+) 260.1313,
found 260.1310.
1
Compound 3bt. 62 mg, 72% yield, yellow oil; H NMR (CDCl3,
400 MHz) δ 3.83 (t, J = 8.1 Hz, 2 H), 4.46 (t, J = 7.7 Hz, 2 H), 6.88 (s, 1
H), 7.34−7.38 (m, 6 H), 7.43−7.51 (m, 4 H); 13C NMR (CDCl3, 100
MHz) δ 45.2, 62.5, 85.4, 90.8, 117.5, 122.1, 128.4, 128.7, 128.7, 128.8,
128.9, 131.7, 134.2, 134.8, 156.0; MS (EI, m/z): 290 (8), 289 (M+, 49),
288 (18), 244 (71), 230 (33); HRMS (ESI) calcd for C19H15NO2 (M+)
289.1103, found 289.1105.
Compound 3ca. 73 mg, 86% yield, white solid, mp 126−128 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.67 (t, J = 7.9 Hz, 2 H), 4.44 (t, J = 8.0 Hz,
2 H), 6.81 (s, 1 H), 7.06−7.08 (m, 2 H), 7.36−7.41 (m, 5 H), 7.45 (d, J
= 7.6 Hz, 2 H); 13C NMR (CDCl3, 150 MHz) δ 45.2, 62.5, 115.7 (d, J =
21.6 Hz), 125.8, 128.7, 128.8, 130.0 (d, J = 8.1 Hz), 131.3 (d, J = 3.4
Hz), 134.3, 136.0, 156.2, 162.1 (d, J = 248.7 Hz); 19F NMR (CDCl3,
565 MHz) δ −112.5; MS (EI, m/z): 285 (11), 284 (79), 283 (M+, 73),
238 (47), 224 (68); HRMS (ESI) calcd for C17H14FNO2 (M+)
283.1009, found 283.1017.
Compound 3ks. 57 mg, 80% yield, white solid, mp 106−108 °C; 1H
NMR (CDCl3, 600 MHz) δ 0.89 (t, J = 7.4 Hz, 3 H), 1.36−1.42 (m, 2
H), 2.07−2.13 (m, 2 H), 5.35−5.40 (m, 1 H), 6.32 (d, J = 15.4 Hz, 1
H), 6.47 (s, 1 H), 6.63−6.68 (m, 2 H), 6.88 (s, 1 H), 7.15−2.20 (m, 2
H), 7.23 (s, 1 H), 7.39 (s, 1 H); 13C NMR (CDCl3, 150 MHz) δ 13.6,
22.1, 34.4, 119.4, 126.6, 128.1, 128.4, 128.6, 129.4, 129.7, 133.6, 133.8,
134.0, 136.8; HRMS (ESI) calcd for C16H19N2 (M+H)+ 239.1548,
found 239.1526.
Compound 3mi.13 93 mg, 87% yield, colorless oil; 1H NMR
(CD3COCD3, 600 MHz) δ 3.67 (s, 3 H), 3.77 (s, 3 H), 6.61−6.66 (m,
2 H), 6.70−6.75 (m, 3 H), 6.85−6.89 (m, 2 H), 6.94−7.15 (m, 7 H),
7.65−7.69 (m, 1 H); 13C NMR (CD3COCD3, 150 MHz) δ 55.4, 55.6,
104.3, 112.1, 114.5, 114.8, 120.9, 121.6, 122.8, 124.0, 127.7, 128.4,
129.3, 129.7, 130.8, 131.9, 134.3, 136.4, 160.0, 160.9.
Compound 3da. 73 mg, 81% yield, white solid, mp 131−133 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.68 (t, J = 8.0 Hz, 2 H), 4.46 (t, J = 7.9 Hz,
2 H), 6.79 (s, 1 H), 7.33−7.36 (m, 4 H), 7.37−7.42 (m, 3 H), 7.44−
7.46 (m, 2 H); 13C NMR (CDCl3, 150 MHz) δ 45.3, 62.5, 125.7, 125.9,
128.8, 128.9, 129.0, 129.4, 129.5, 133.7, 135.0, 136.0, 156.1; MS (EI, m/
z): 301 (31), 299 (M+, 100), 254 (11), 240 (34), 212 (81); HRMS
(ESI) calcd for C17H14ClNO2 (M+) 299.0713, found 299.0717.
Compound 3ea. 82 mg, 91% yield, white solid, mp 136−138 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.61 (t, J = 7.9 Hz, 2 H), 4.37 (t, J = 8.2 Hz,
2 H), 6.97 (s, 1 H), 7.28−7.31 (m, 2 H), 7.41−7.46 (m, 4 H), 7.52−
7.54 (m, 3 H); 13C NMR (CDCl3, 150 MHz) δ 45.6, 62.5, 123.2, 126.1,
126.9, 128.7, 129.0, 129.1, 129.2, 129.5, 133.6, 133.8, 135.8, 136.6,
156.2; MS (EI, m/z): 301 (33), 299 (M+, 96), 264 (100), 220 (59), 212
(91); HRMS (ESI) calcd for C17H14ClNO2 (M+) 299.0713, found
299.0725.
Compound 3fa. 70 mg, 70% yield, white solid, rr > 10:1, mp 149−
151 °C; 1H NMR (CDCl3, 400 MHz) δ 3.62 (t, J = 7.8 Hz, 2 H), 4.39
(t, J = 8.2 Hz, 2 H), 6.87 (s, 1 H), 7.27−7.29 (m, 1 H), 7.43−7.46 (m, 5
H), 7.49−7.52 (m, 2 H); 13C NMR (CDCl3, 100 MHz) δ 45.5, 62.5,
122.1, 126.2, 127.3, 128.8, 129.3, 129.4, 129.8, 132.5, 134.1, 134.3,
135.4, 137.1, 155.9; MS (EI, m/z): 335 (57), 333 (M+, 95), 300 (27),
248 (63), 246 (100); HRMS (ESI) calcd for C17H13Cl2NO2 (M+)
333.0323, found 333.0329.
Compound 3na. 81 mg, 84% yield, white solid, mp 132−134 °C; 1H
NMR (CDCl3, 600 MHz) δ 6.77 (d, J = 7.6 Hz, 2 H), 6.94 (d, J = 3.2
Hz, 1 H), 7.05−7.08 (m, 1 H), 7.12−7.17 (m, 3 H), 7.19−7.20 (m, 2
H), 7.21−7.22 (m, 1 H), 7.23−7.24 (m, 2 H), 7.35−7.39 (m, 3 H),
7.47−7.48 (m, 1 H); 13C NMR (CDCl3, 150 MHz) δ 102.7, 103.2,
116.3, 118.5, 121.8, 125.6, 125.7, 125.8, 128.2, 128.4, 128.5, 128.8,
129.1, 129.9, 131.1, 134.0, 135.0, 135.1, 137.5; MS (EI, m/z): 321 (18),
320 (M+, 58), 319 (73), 243 (13), 178 (100); HRMS (ESI) calcd for
C23H17N2 (M + H)+ 321.1392, found 321.1411.
Compound 3oa.14 63 mg, 80% yield, white solid, mp 116−118 °C;
1H NMR (CDCl3, 600 MHz) δ 2.14−2.19 (m, 2 H), 2.55 (t, J = 8.2 Hz,
2 H), 3.52 (t, J = 7.0 Hz, 2 H), 6.96 (s, 1 H), 7.29−7.31 (m, 1 H), 7.38−
7.42 (m, 7 H), 7.46−7.57 (m, 2 H); 13C NMR (CDCl3, 150 MHz) δ
19.1, 31.1, 48.4, 125.6, 126.5, 127.8, 128.0, 128.4, 128.5, 128.7, 135.5,
135.7, 136.4, 175.0.
Compound 5. To a solution of 3br (87 mg, 0.3 mmol) in 1 mL of
toluene was added diethyl acetylenedicarboxylate (61 mg, 0.36 mmol).
After stirring at reflux for 16 h, the reaction mixture was concentrated.
Column chromatography on silica gel (petroleum ether/EtOAc = 1:1)
Compound 3ga. 83 mg, 86% yield, white solid, mp 148−150 °C; 1H
NMR (CDCl3, 600 MHz) δ 1.35 (s, 9 H), 3.71 (t, J = 8.0 Hz, 2 H), 4.47
(t, J = 8.3 Hz, 2 H), 6.85 (s, 1 H), 7.35−7.36 (m, 1 H), 7.39−7.42 (m, 6
H), 7.46−7.48 (m, 2 H); 13C NMR (CDCl3, 150 MHz) δ 31.1, 34.6,
45.1, 62.5, 125.6, 125.7, 126.8, 128.1, 128.5, 128.7, 132.1, 133.5, 136.4,
151.2, 156.3; MS (EI, m/z): 322 (20), 321 (M+, 100), 306 (89), 219
(55), 207 (3); HRMS (ESI) calcd for C21H23NO2 (M+) 321.1729,
found 321.1736.
1
gave 93 mg (67% yield) of 5 as a white solid, mp 134−136 °C; H
NMR (CDCl3, 600 MHz) δ 0.99 (t, J = 7.1 Hz, 3 H), 1.04 (t, J = 7.1 Hz,
3 H), 3.08−3.12 (m, 1 H), 3.74 (q, J = 8.7 Hz, 1 H), 3.93−4.07 (m, 5
H), 4.12−4.16 (m, 1 H), 4.67 (dd, J = 4.2, 7.0 Hz, 1 H), 5.34 (d, J = 7.0
Hz, 1 H), 5.66 (dd, J = 0.8, 4.2 Hz, 1 H), 7.27−7.42 (m, 10 H); 13C
NMR (CDCl3, 150 MHz) δ 13.6, 13.6, 43.3, 44.5, 46.7, 60.9, 61.0, 61.7,
117.7, 127.2, 127.5, 128.1, 128.4, 128.7, 128.9, 133.4, 133.6, 135.7,
139.2, 140.8, 155.1, 166.5, 166.7; MS (EI, m/z): 461 (M+, 4), 460 (21),
459 (100), 414 (18), 380 (20); HRMS (ESI) calcd for C27H27NO6
(M+) 461.1838, found 461.1841.
Compound 3ha. 80 mg, 90% yield, white solid, mp 141−143 °C; 1H
NMR (CDCl3, 600 MHz) δ 3.69 (t, J = 7.9 Hz, 2 H), 3.82 (s, 3 H), 4.45
(t, J = 8.2 Hz, 2 H), 6.82 (s, 1 H), 6.92 (d, J = 8.7 Hz, 2 H), 7.31−7.35
(m, 1 H), 7.37−7.41 (m, 4 H), 7.45 (d, J = 7.7 Hz, 2 H); 13C NMR
(CDCl3, 150 MHz) δ 45.1, 55.1, 62.5, 114.1, 125.5, 126.6, 127.6, 128.4,
128.7, 129.7, 132.4, 136.4, 156.4, 159.3; MS (EI, m/z): 296 (28), 295
(M+, 100), 236 (15), 208 (83), 193 (35); HRMS (ESI) calcd for
C18H17NO3 (M+) 295.1208, found 295.1217.
ASSOCIATED CONTENT
■
S
* Supporting Information
Spectroscopic data of products 3 and 5, as well as the X-ray data
of 3bm. This material is available free of charge via the Internet
at http://pubs.acs.org.
Compound 3ia. 81 mg, 90% yield, colorless oil; 1H NMR (CDCl3,
600 MHz) δ 0.88 (t, J = 7.0 Hz, 3 H), 1.25−1.37 (m, 10 H), 1.46−1.54
(m, 2 H), 2.19−2.23 (m, 2 H), 3.64 (t, J = 8.0 Hz, 2 H), 4.46 (t, J = 8.2
Hz, 2 H), 6.00 (t, J = 7.2 Hz, 1 H), 7.31−7.35 (m, 5 H); 13C NMR
(CDCl3, 150 MHz) δ 14.0, 22.6, 28.2, 28.8, 29.2, 29.4, 29.5, 31.8, 45.6,
62.2, 125.8, 128.1, 128.6, 130.8, 133.6, 135.7, 156.4; MS (EI, m/z): 302
(6), 301 (M+, 25), 256 (7), 214 (33), 202 (79); HRMS (ESI) calcd for
C19H27NO2 (M+) 301.2042, found 301.2045.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gangguo@zjnu.cn (G.Z.).
Compound 3ia-d. It was prepared from 1i, 5 equiv of D2O, and 0.5
equiv of (PhBO)3 under the standard conditions, 79 mg, 87% yield,
colorless oil; 1H NMR (CDCl3, 600 MHz) δ 0.88 (t, J = 6.8 Hz, 3 H),
Notes
The authors declare no competing financial interest.
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Soc. 2001, 123, 9918. (b) Lautens, M.; Yoshida, M. Org. Lett. 2002, 4,
123. (c) Panteleev, J.; Huang, R. Y.; Lui, E. K. J.; Lautens, M. Org. Lett.
2011, 13, 5314. (d) Genin, E.; Michelet, V.; Genet, J.-P. J. Organomet.
̂
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation of
China (21172199), the Natural Science Foundation of Zhejiang
Province (LR12B02001 and LY14B020002), and Zhejiang
Normal University.
Chem. 2004, 689, 3820. (e) Zhang, W.; Liu, M.; Wu, H.; Ding, J.;
Cheng, J. Tetrahedron Lett. 2008, 49, 5214. (f) Arcadi, A.; Aschi, M.;
Chiarini, M.; Ferrara, G.; Marinelli, F. Adv. Synth. Catal. 2010, 352, 493.
(g) Gourdet, B.; Rudkin, M. E.; Lam, H. W. Org. Lett. 2010, 12, 2554.
(9) (a) Lu, Z.; Kong, W.; Yuan, Z.; Zhao, X.; Zhu, G. J. Org. Chem.
2011, 76, 8524. (b) Lu, Z.; Cui, W.; Xia, S.; Bai, Y.; Luo, F.; Zhu, G. J.
Org. Chem. 2012, 77, 9871. (c) Lu, Z.; Xu, X.; Yang, Z.; Kong, L.; Zhu,
G. Tetrahedron Lett. 2012, 53, 3433.
REFERENCES
■
(1) (a) Yet, L. Chem. Rev. 2003, 103, 4283. (b) Carbery, D. R. Org.
Biomol. Chem. 2008, 6, 3455. (c) 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
and references therein.
(2) For selected reports on the synthesis of enamides via
hydroaddition of ynamides, see: (a) Mulder, J. A.; Kurtz, K. C. M.;
Hsung, R. P.; Coverdale, H.; Frederick, M. O.; Shen, L.; Zificsak, C. A.
Org. Lett. 2003, 5, 1547. (b) Kramer, S.; Dooleweerdt, K.; Lindhardt, A.
(10) Yang, Y.; Wang, L.; Zhang, J.; Jin, Y.; Zhu, G. Chem. Commun.
2014, 50, 2347.
(11) For the Pd-catalyzed addition of boronic acids to alkynes, see:
(a) Oh, C. H.; Jung, H. H.; Kim, K. S.; Kim, N. Angew. Chem., Int. Ed.
2003, 42, 805. (b) Kim, N.; Kim, K. S.; Gupta, A. K.; Oh, C. H. Chem.
Commun. 2004, 618. (c) Zeng, H.; Hua, R. J. Org. Chem. 2008, 73, 558.
(d) Xu, X.; Chen, J.; Gao, W.; Wu, H.; Ding, J.; Su, W. Tetrahedron
2010, 66, 2433. (e) Bai, Y.; Yin, J.; Kong, W.; Mao, M.; Zhu, G. Chem.
Commun. 2013, 49, 7650.
(12) For other catalytic versions, see: (a) Shirakawa, E.; Takahashi, G.;
Tsuchimoto, T.; Kawakami, Y. Chem. Commun. 2001, 2688. (b) Lin, P.-
S.; Jeganmohan, M.; Cheng, C.-H. Chem.Eur. J. 2008, 14, 11296.
(c) Yamamoto, Y.; Kirai, N.; Harada, Y. Chem. Commun. 2008, 2010.
(13) Roche, M.; Frison, G.; Brion, J.-D.; Provot, O.; Hamze, A.; Alami,
M. J. Org. Chem. 2013, 78, 8485.
(14) Gou, Q.; Deng, B.; Zhang, H.; Qin, J. Org. Lett. 2013, 15, 4604.
(15) In fact, N-sulfonyl ynamides are not suitable substrates for this
reaction, due to the occurrence of trans-addition; see ref 10.
Furthermore, N-alkynyl tert-butyloxycarbamates are not applicable to
this reaction because of the formation of 2-oxazolones; for the related
reference, see: Lu, Z.; Xu, X.; Yang, Z.; Kong, L.; Zhu, G. Tetrahedron
Lett. 2012, 53, 3433.
T.; Rottlander, M.; Skrydstrup, T. Org. Lett. 2009, 11, 4208. (c) Fadel,
̈
A.; Legrand, F.; Evano, G.; Rabasso, N. Adv. Synth. Catal. 2011, 353,
263. (d) Compain, G.; Jouvin, K.; Martin-Mingot, A.; Evano, G.;
Marrot, J.; Thibaudeau, S. Chem. Commun. 2012, 48, 5196. (e) Smith,
D. L.; Goundry, W. R. F.; Lam, H. W. Chem. Commun. 2012, 48, 1505.
(f) Saito, N.; Saito, K.; Sato, H.; Sato, Y. Adv. Synth. Catal. 2013, 355,
853. (g) Sato, A. H.; Ohashi, K.; Iwasawa, T. Tetrahedon Lett. 2013, 54,
1309. (h) Maity, P.; Klos, M. R.; Kazmaier, U. Org. Lett. 2013, 15, 6246.
(3) For selected reports on the synthesis of enamides via
́
carbometalation of ynamides, see: (a) Couty, S.; Liegault, B.; Meyer,
C.; Cossy, J. Org. Lett. 2004, 6, 2511. (b) Chechik-Lankin, H.; Livshin,
S.; Marek, I. Synlett 2005, 2098. (c) Yasui, H.; Yorimitsu, H.; Oshima,
K. Bull. Chem. Soc. Jpn. 2008, 81, 373. (d) Gourdet, B.; Lam, H. W. J.
Am. Chem. Soc. 2009, 131, 3802. (e) Greenaway, R. L.; Campbell, C.
D.; Holton, O. T.; Russell, C. A.; Anderson, E. A. Chem.Eur. J. 2011,
17, 14366. (f) Greenaway, R. L.; Campbell, C. D.; Chapman, H. A.;
Anderson, E. A. Adv. Synth. Catal. 2012, 354, 3187. (g) Gati, W.; Couty,
F.; Boubaker, T.; Rammah, M. M.; Rammah, M. B.; Evano, G. Org. Lett.
2013, 15, 3122. (h) Frischmuth, A.; Knochel, P. Angew. Chem., Int. Ed.
2013, 52, 10084. For a review, see: (i) Minko, Y.; Pasco, M.; Chechik,
H.; Marek, I. Beilstein J. Org. Chem. 2013, 9, 526.
(16) To avoid the interruption of protons, (PhBO)3 was used instead
of PhB(OH)2 in the deuterium experiments.
(17) (a) Cho, C. S.; Motofusa, S.-I.; Ohe, K.; Uemura, S. J. Org. Chem.
1995, 60, 883. (b) Zhou, C.; Larock, R. C. Org. Lett. 2005, 7, 259.
(18) Zhu, G.; Chen, D.; Wang, Y.; Zheng, R. Chem. Commun. 2012,
48, 5796 and references therein.
(4) For selected reports on the synthesis of enamides via
cycloaddition of ynamides, see: (a) Schotes, C.; Mezzetti, A. Angew.
Chem., Int. Ed. 2011, 50, 3072. (b) Smith, D. L.; Chidipudi, S. R.;
Goundry, W. R.; Lam, H. W. Org. Lett. 2012, 14, 4934. (c) Clavier, H.;
Lepronier, A.; Bengobesse-Mintsa, N.; Gatineau, D.; Pellissier, H.;
Giordano, L.; Tenaglia, A.; Buono, G. Adv. Synth. Catal. 2013, 355, 403.
(d) Mackay, W. D.; Fistikci, M.; Carris, R. M.; Johnson, J. S. Org. Lett.
2014, 16, 1626. (e) Dateer, R. B.; Shaibu, B. S.; Liu, R.-S. Angew. Chem.,
Int. Ed. 2012, 51, 113. (f) Karad, S. N.; Bhunia, S.; Liu, R.-S. Angew.
Chem., Int. Ed. 2012, 51, 8722. (g) Pawar, S. K.; Vasu, D.; Liu, R.-S. Adv.
Synth. Catal. 2014, 356, 2411.
(19) For the Diels−Alder reaction of oxazolidin-2-one-substituted
dienamides, see: (a) Hayashi, R.; Ma, Z.-X.; Hsung, R. P. Org. Lett.
2012, 14, 252. (b) Saito, N.; Saito, K.; Shiro, M.; Sato, Y. Org. Lett.
2011, 13, 2718. (c) Gourdet, B.; Rudkin, M. E.; Watts, C. A.; Lam, H.
W. J. Org. Chem. 2009, 74, 7849 and references therein.
(20) Liu, Y.; Li, D.; Park, C.-M. Angew. Chem., Int. Ed. 2011, 50, 7333.
(5) For other recent reports on the synthesis of enamides by
functionalization of ynamides, see: (a) Rettenmeier, E.; Schuster, A. M.;
Rudolph, M.; Rominger, F.; Gade, C. A.; Hashmi, A. S. K. Angew.
Chem., Int. Ed. 2013, 52, 5880. (b) Nishimura, T.; Takiguchi, Y.;
Maeda, Y.; Hayashi, T. Adv. Synth. Catal. 2013, 355, 1374.
(c) Heffernan, S. J.; Beddoes, J. M.; Mahon, M. F.; Hennessy, A. J.;
Carbery, D. R. Chem. Commun. 2013, 49, 2314. (d) Wang, X.-N.;
Winston-McPherson, G. N.; Walton, M. C.; Zhang, Y.; Hsung, R. P.;
DeKorver, K. A. J. Org. Chem. 2013, 78, 6233. (e) Brioche, J.; Meyer,
C.; Cossy, J. Org. Lett. 2013, 15, 1626. (f) Walker, P. R.; Campbell, C.
D.; Suleman, A.; Carr, G.; Anderson, E. A. Angew. Chem., Int. Ed. 2013,
52, 9139. (g) Kong, Y.; Jiang, K.; Cao, J.; Fu, L.; Yu, L.; Lai, G.; Cui, Y.;
Hu, Z.; Wang, G. Org. Lett. 2013, 15, 422.
(6) 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.; Coste, A.; Jouvin, K. Angew. Chem., Int.
Ed. 2010, 49, 2840.
(7) Gourdet, B.; Smith, D. L.; Lam, H. W. Tetrahedron 2010, 66, 6026.
(8) For the Rh-catalyzed addition of boronic acids to alkynes, see:
(a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem.
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