N-Acylsaccharins as Amide-Based Arylating Reagents via Chemoselective N-C Cleavage: Pd-Catalyzed Decarbonylative Heck Reaction

Article abstract of DOI:10.1021/acs.joc.6b02294

Palladium-catalyzed decarbonylative Heck reaction of amides by chemoselective N-C activation using N-acylsaccharins as coupling partners has been accomplished. These studies represent only the second example of amide-Heck reactions reported to date. A broad range of electronically diverse amide and olefin coupling partners is amenable to this transformation. Orthogonal site-selective Heck cross-couplings by C-Br/N-C cleavage and mechanistic studies are reported. This report introduces readily available, bench-stable, cheap, and benign N-acylsaccharins as aryl transfer reagents to access versatile aryl-metal intermediates.

Full text of DOI:10.1021/acs.joc.6b02294

Note
pubs.acs.org/joc
N‑Acylsaccharins as Amide-Based Arylating Reagents via
Chemoselective N−C Cleavage: Pd-Catalyzed Decarbonylative Heck
Reaction
Chengwei Liu, Guangrong Meng, and Michal Szostak*
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States
S
* Supporting Information
ABSTRACT: Palladium-catalyzed decarbonylative Heck re-
action of amides by chemoselective N−C activation using N-
acylsaccharins as coupling partners has been accomplished.
These studies represent only the second example of amide-
Heck reactions reported to date. A broad range of electroni-
cally diverse amide and olefin coupling partners is amenable to
this transformation. Orthogonal site-selective Heck cross-
couplings by C−Br/N−C cleavage and mechanistic studies are
reported. This report introduces readily available, bench-stable, cheap, and benign N-acylsaccharins as aryl transfer reagents to
access versatile aryl-metal intermediates.
he ability to perform selective functionalization reactions
represents an enabling approach in organic synthesis.
T
Since the first report in 1968, the Heck reaction has been
established as one of the most powerful, chemoselective
transition-metal-catalyzed transformations in organic synthe-
sis.1,2 The classic Heck reaction furnishes functionalized olefins
that are essential structural motifs for the synthesis of
pharmaceuticals, organic materials, agrochemicals, and complex
natural products in both academic and industrial settings.3 In
particular, the use of feedstock alkenes as nucleophilic coupling
partners has become a central tool for industrial manufacturing
due to lowering the cost associated with olefin prefunctional-
ization.4 Methods have been reported for the cross-coupling of
aryl halides,5a−d triflates,5e pseudohalides,5f and diazonium
salts.5g,h While oxidative Heck reactions of carboxylic acids,6a
phosphonic acids,6b and hydrocarbons6c have been developed,
these methods require stoichiometric oxidants, proceed with
limited scope or control of regioselectivity.2
Figure 1. Classic and aroyl electrophiles in the Heck reaction.
bond toward metal insertion is the amide nN → π*CO
resonance (planar amides, ca. 15−20 kcal/mol).10 A general
use of amides as coupling partners in the Heck reaction would
have a potential to extend to the functionalization of
biomolecules and large scale industrial olefinations using
bench-stable, chemoselective, low-cost acid amide reagents.
We have recently established the first decarbonylative Heck
reaction of amides using N-glutarimides as coupling partners by
steric distortion (Figure 2A).11 The first decarbonylative Suzuki
and direct decarbonylative C−H activation of N-glutarimide
amides using Ni and Rh catalysis have been developed.12
Recently, Ni-catalyzed decarbonylative borylation of amides by
N−C cleavage has been accomplished.13,14 These reactions
proceed via selective N−C insertion/decarbonylation, in which
the facility of metal insertion is controlled by amide
destabilization.15 Extensive studies on amide geometry provide
additional evidence for the distortion of amides undergoing
metal insertion.16 To expand the generality of decarbonylative
In contrast, decarbonylative Heck reactions of stable aroyl
electrophiles, such as esters and amides, remain a significant
challenge (Figure 1).7 The advantages of using esters and
amides in comparison with typical cross-coupling partners
include (i) low cost; (ii) high stability; (iii) ready availability;
and (iv) unprecedented potential for unconventional cross-
couplings with orthogonal selectivity controlled by the facility
of metal insertion into the C−O or C−N bond, which is not
possible with unstable aroyl halides and anhydrides. Mechanis-
tically, metal insertion into a weak C(CO)−X bond (X = O, N)
enables the use of orthogonal coupling partners to aryl(aroyl)
halides by decarbonylation of the initially formed acyl-metal
species.8 However, despite the significant progress in the
development of ester electrophiles for Heck reactions,7c,d the
potential of amides as electrophilic coupling partners remains
to be explored.2f,9 The chief challenge in activating the amide
Received: September 18, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b02294
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The Journal of Organic Chemistry
Note
Table 1. Optimization of Pd-Catalyzed Decarbonylative
a
Heck Reaction of N-Acylsaccharins by N−C Cleavage
entry
catalyst
ligand
solvent
yield (%)
1
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
NMP
NMP
NMP
NMP
toluene
dioxane
NMP
NMP
NMP
NMP
toluene
dioxane
NMP
NMP
NMP
NMP
NMP
NMP
98
63
41
<5
<5
19
43
28
<5
53
26
36
25
50
40
<5
75
92
2
3
4
5
6
7
8
9
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
b
c
d
e
f
b
10
11
12
13
14
15
16
17
18
c
d
e
Figure 2. (a) Decarbonylative N−C cleavage in amides. (b) Saccharins
as electrophilic functional group transfer reagents.
g
LiBr
g,h,i
Heck reactions by N−C cleavage, we considered N-
acylsaccharins as bench-stable, amide-based, electrophilic
coupling partners.17 Recently, N-acylsaccharins have emerged
as efficient functional group transfer reagents in metal-catalyzed
formylation18a and alkoxycarbonylation.18b We have developed
conditions for the Suzuki-Miyaura cross-coupling of N-
acylsaccharins to yield ketones with exclusive RC(O)−
coupling selectivity (acyl transfer, Figure 2B).18c
Herein, we report for the first time the Pd-catalyzed
decarbonylative Heck reaction of N-acylsaccharins as electro-
philic coupling partners by highly chemoselective N−C bond
cleavage/decarbonylation. The following features of our
findings are noteworthy: (i) low-price, availability, benign
nature of saccharin; (ii) bench-stability and ease of crystal-
lization of N-acylsaccharins, which allows to avoid sensitive
intermediates during cross-couplings; (iii) excellent functional
group tolerance and wide range of electronically diverse amide
and olefin coupling partners that undergo this transformation;
(iv) operationally simple, base-free, ligand-free conditions; (v)
the first iterative Heck cross-couplings using carbonyl electro-
philes by site-selective C−N/C−Br cleavage; (vi) most
importantly, this report introduces readily available, bench-
stable, cheap N-acylsaccharins as aryl transfer reagents for
metal-catalyzed transformations via metal-insertion/decarbon-
ylation to access versatile aryl metal intermediates. Our studies
demonstrate the highest reactivity of N-acylsaccharins in amide
N−C cleavage discovered to date.18c
The Heck cross-coupling of N-benzoylsaccharin (1) with n-
butyl acrylate (2) was investigated as a model reaction to
identify the most active catalyst system. Selected key
optimization results obtained during the optimization studies
are summarized in Table 1. Under our standard conditions, 1
underwent the decarbonylative N−C coupling in excellent 98%
yield (entry 1). Notably, we found that the presence of halide
salts had a negative impact on the reaction efficiency (entries
2−15).19 Similarly, the use of external nucleophiles7 (entries 4
and 13) and other solvents (entries 5−6 and 11−12) resulted
in a diminished yield of the arylation product. We hypothesize
that these effects are consistent with high electrophilicity of N-
g,i,j
a
Conditions: 1 (0.20 mmol), R-CHCH2 (2.0 equiv), catalyst (3 mol
b
%), ligand (9 mol%), 160 °C, 18 h. R = CO2n-Bu. R-CHCH2 (1.2
c
d
e
f
equiv). Isoquinoline (0.10 equiv). 120 °C. 80 °C. Ligand (1 equiv).
g
h
i
j
R = Ph. 180 °C. Catalyst (5 mol%). R-CHCH2 (3 equiv).
acylsaccharins and competing nucleophilic addition. Mechanis-
tically, the reaction ensues at 80 °C with complete aryl- vs acyl-
selectivity (entries 8−9 and 14−15), consistent with the high
propensity of the N−C bond in N-acylsaccharins for metal
insertion/decarbonylation.18a−c Furthermore, we were pleased
to find that after small adjustment of the reaction conditions,
the process could be extended to valuable styrene nucleophiles
(entries 16−18). The use of other Pd precursors, including
Pd(OAc)2, PdBr2, and PdI2 resulted in low reaction efficiency
(not shown). Importantly, under the optimized conditions,
products resulting from the acyl-transfer (cf. arylation) were
not observed,18c demonstrating efficient decarbonylation under
these conditions.8 Furthermore, cleavage of the alternative C−
SO2 bond was not observed.20 Overall, the optimized
conditions compare favorably with other methods for the
decarbonylative Heck reactions in terms of operational
simplicity and reaction efficiency (vide infra).7,11
With the optimized conditions in hand, the substrate scope
was next investigated (Table 2). As shown, a wide range of
electronically varied substrates containing diverse functional
groups underwent the cross-coupling in high yields and with
generally excellent regioselectivity (entries 1−21). Neutral
(3a), electron-rich (3b), electron-poor (3c), fluoro- (3d),
chloro- (3e), bromo- (3f), ester- (3g), and nitro-containing
substrates (3h) were perfectly tolerated, affording the
corresponding olefins in 63−82% yields. Debromination was
not observed. Moreover, ortho-substituted N-acylsaccharins
(3i, 3j) coupled in high yields. The scope of the reaction with
respect to the olefin component is also broad and encompasses
α,β-unsaturated esters (3k, 3o), amides (3l), and nitriles (3m).
Disubstituted olefins are suitable coupling partners (3n).21a
Aliphatic alkenes can also be used (3p); however, these
B
DOI: 10.1021/acs.joc.6b02294
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The Journal of Organic Chemistry
Note
a
Table 2. Pd-Catalyzed Decarbonylative Heck Cross-Coupling of N-Acylsaccharins by N−C Cleavage: Substrate Scope
a
b
c
1 (0.20 mmol), R-CHCH2 (2.0 equiv), PdCl2 (3 mol%), NMP, 160 °C, selectivity >20:1. Selectivity: 5.80:2.20:1.00. Isomers
d
(8.44:2.72:5.99:1.00). 1 (1.0 equiv), R-CHCH2 (3.0 equiv), PdCl2 (5 mol%). 2,1/1,2:91:9 (3q), 95:5 (3r), 81:19 (3s), 75:25 (3s′), 92:8 (3t).
substrates afford mixture of isomers, as expected.21b,7c Finally,
Scheme 1. Mechanistic Studies
electronically diverse styrenes underwent coupling in good
yields and with high regioselectivity. For these substrates a
higher catalyst loading (5 mol%) was used to obtain optimum
results. Only monoarylation products were observed in all
examples examined.7d,e In all cases, exclusive formation of E
isomers was found. At this stage, saccharin recovery has not
been performed as recovery from highly polar solvents is not
straightforward. The reaction enables synthesis of olefins with
diverse electrophilic functional handles for further manipu-
lation. Of note is the synthesis of a common UV−B sunscreen
produced industrially (3o).4a While the reaction requires NMP
as a polar solvent to achieve optimum yields, the reaction does
not require expensive oxidants and the scope of the reaction is
not limited to ortho-substituted substrates as is the case with
oxidative Heck reactions.6−8 To assess the utility of the process,
the coupling was performed on a 2.0 mmol scale using n-butyl
acrylate and styrene, and gave 3a and 3q in 79% (>20:1
selectivity) and 87% (92:8 selectivity) isolated yields,
respectively, attesting to the synthetic utility of the method.
Intrigued by the high reactivity of N-acylsaccharins (twisted
amide bond: τ = 23.0°, χN = 12.5°),18c we conducted
H2CC-MeCO2n-Bu (Scheme 1B). (3) Experiments with
preliminary studies to gain insight into the reaction mechanism
(Scheme 1).22 (1) Intermolecular competition experiments
between differently substituted N-acylsaccharins indicated that
electron-deficient substrates react preferentially (Scheme 1A).
(2) Experiments with different olefins established the following
reactivity order: H2CCH−CO2n-Bu ≈ H2CCH-Ph >
aroyl electrophiles revealed the following order of reactivity: N-
acylsaccharins > N-glutarimides ≈ (Ar−CO)2O ≫ Ar−CO2R
(Scheme 1C). (4) Electronic effects observed in the
regioselectivity of the arylation with styrenes (styrene: ρ-value
of 1.21, R2 = 0.99; amide: ρ+-value of 0.46, R2 = 0.90) indicate
an increase in the arylation regioselectivity of electron-deficient
C
DOI: 10.1021/acs.joc.6b02294
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The Journal of Organic Chemistry
Note
and dried. The crude product was purified by recrystallization
(methanol or toluene) to give analytically pure product. All N-
acylsaccharins are bench-stable solids with no decomposition observed
while storing on benchtop at room temperature for a period of six
months.
olefins and electron-deficient amides. These preliminary studies
are consistent with the initial metal insertion into the amide
N−C bond;9 olefin insertion might be a kinetically relevant step
in the reaction.22b The high reactivity of N-acylsaccharins (cf.
glutarimides)11 bodes well for further applications in decarbon-
ylative cross-couplings by amide N−C cleavage.
General Procedure for Heck Cross-Coupling. An oven-dried
vial equipped with a stir bar was charged with amide substrate (neat,
1.0 equiv), PdCl2 (typically, 3 mol %), and olefin (typically, 2.0 equiv),
placed under a positive pressure of argon, and subjected to three
evacuation/backfilling cycles under high vacuum. N-Methyl-2-
pyrrolidinone (NMP, 0.25 M) was added with vigorous stirring at
room temperature, the reaction mixture was placed in a preheated oil
bath at 160 °C, and stirred for the indicated time at 160 °C. After the
indicated time, the reaction mixture was cooled down to room
temperature and diluted with CH2Cl2 (5 mL). The sample was
We highlighted the synthetic utility of N-acylsaccharins as
orthogonal cross-coupling partners in iterative site-specific C−
N/C−Br cross-coupling (Scheme 2).23 The Heck cross-
Scheme 2. Iterative Heck Cross-Coupling of N-
Acylsaccharins: C−N vs C−Br Cleavage
1
analyzed by H NMR (CDCl3, 500 MHz) and/or GC-MS to obtain
conversion, selectivity, and yield using internal standard and
comparison with authentic samples. In all examples reported in the
manuscript 2,1/1,2-selectivity was obtained by analysis of the crude
reaction mixture. Unless indicated otherwise, in all examples reported
in the manuscript single olefin isomers were observed (E/Z > 98:2).
Unless indicated otherwise, only monoarylated products were
observed (mono/diarylation selectivity >98:2). All yields reported in
the manuscript refer to isolated yields after purification by
chromatography on silica gel (hexanes/EtOAc). Unless indicated
otherwise, in all examples reported in the manuscript single olefin
regioisomers were obtained after the purification.
Representative Procedure for Heck Cross-Coupling. An oven-
dried vial equipped with a stir bar was charged with N-
benzoylsaccharin (neat, 57.5 mg, 0.2 mmol), PdCl2 (1.1 mg, 3 mol
%) and n-butyl acrylate (51.3 mg, 2.0 equiv), placed under a positive
pressure of argon, and subjected to three evacuation/backfilling cycles
under high vacuum. N-Methyl-2-pyrrolidinone (0.25 M) was added
with vigorous stirring at room temperature, the reaction mixture was
placed in a preheated oil bath at 160 °C, and stirred for 18 h at 160 °C.
After the indicated time, the reaction mixture was cooled down to
room temperature and diluted with CH2Cl2 (5 mL). The sample was
analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain
conversion, selectivity, and yield using internal standard and
comparison with authentic samples. 2,1/1,2 > 98:2. E/Z > 98:2.
Purification by chromatography on silica gel (hexanes/EtOAc = 10/1)
afforded the title product. Yield 82% (33.5 mg, 0.164 mmol). Colorless
oil. Characterization data are included in the section below.
2.0 mmol scale coupling was performed according to the
representative procedure using N-benzoylsaccharin (neat, 575 mg,
2.0 mmol), PdCl2 (11 mg, 3 mol%) and n-butyl acrylate (513 mg, 2.0
equiv) in N-methyl-2-pyrrolidinone (0.25 M) at 160 °C for 18 h. 2,1/
1,2 > 98:2. E/Z > 98:2. Purification by chromatography on silica gel
(hexanes/EtOAc = 10/1) afforded 3a. Yield 79% (323 mg, 1.58
mmol). Colorless oil. Characterization data are included in the section
below.
coupling of aryl bromides can be achieved by Pd/Pt-Bu3-
catalysis,5d,22c leaving the amide bond in N-acylsaccharins intact
(Scheme 2, top). Alternatively, the amide N−C cross-coupling
can be followed by the C−Br cleavage (Scheme 2, bottom). To
our knowledge, this is the first sequential cross-coupling
involving decarbonylative Heck reactions.2,3,7 The iterative
cross-coupling is facilitated by the high reactivity of N-
acylsaccharins18 and the ease of purification of intermediates
by recrystallization.17
In summary, we have reported the first Pd-catalyzed
decarbonylative Heck cross-coupling of N-acylsaccharins by
chemoselective N−C cleavage. A variety of amide and olefin
substrates is suitable for this reaction. The sequential Heck
coupling of C−Br and C−N bonds has been demonstrated for
the first time. N-Acylsaccharins are air-stable, crystalline solids
that show comparable reactivity to N-glutarimide amides. The
discovery that N-acylsaccharins serve as selective bench-stable
aryl transfer reagents may enable the development of a broad
range of novel metal-catalyzed transformations.
2.0 mmol scale coupling using styrene was performed according to
the representative procedure using N-benzoylsaccharin (neat, 575 mg,
2.0 mmol), PdCl2 (18 mg, 5 mol%) and styrene (624 mg, 3.0 equiv) in
N-methyl-2-pyrrolidinone (0.25 M) at 160 °C for 18 h. 2,1/1,2 = 92:8.
E/Z > 98:2. Purification by chromatography on silica gel (hexanes/
EtOAc = 10/1) afforded 3q. Yield 87% (314 mg, 1.74 mmol). White
solid. Characterization data are included in the section below.
EXPERIMENTAL SECTION
■
General Methods. All starting materials reported in the
manuscript have been prepared according to the method reported
previously.24 All compounds reported in this manuscript have been
previously reported or are commercially available unless noted
otherwise. Spectroscopic data matched literature values. General
methods have been published.18c
N-Benzoylsaccharin (1a).24 Yield 95% (0.82 g). White solid. H
1
NMR (500 MHz, CDCl3) δ 8.16−8.15 (d, J = 7.7 Hz, 1 H), 8.05−8.01
(m, 2 H), 7.96−7.94 (t, J = 7.9 Hz, 1 H), 7.80−7.78 (d, J = 8.3 Hz, 2
H), 7.70−7.67 (t, J = 7.1 Hz, 1 H), 7.55−7.52 (t, J = 7.7 Hz, 2 H). 13C
NMR (125 MHz, CDCl3) δ 166.4, 157.5, 138.5, 136.4, 134.9, 133.9,
132.4, 129.6, 128.5, 126.4, 125.6, 121.3. MS = 287.0 (EI).
General Procedure for Amide Synthesis. An oven-dried flask
(25 mL) equipped with a stir bar was charged with amine (typically,
3.0 mmol, 1.0 equiv), triethylamine (typically, 1.0 equiv), and N,N-
dimethylacetamide (DMAc, typically, 0.75 M), placed under a positive
pressure of argon, and subjected to three evacuation/backfilling cycles
under high vacuum. Acyl chloride (typically, 1.0 equiv) was added
dropwise to the reaction mixture with vigorous stirring at 0 °C, and the
reaction mixture was stirred for 1 h at room temperature. After the
indicated time, the reaction mixture was diluted with H2O (5 mL).
The solid was collected by filtration, washed with Et2O (1 × 10 mL),
N-4-Methoxylbenzoylsaccharin (1b).18c Yield 81% (0.77 g). White
solid. 1H NMR (500 MHz, CDCl3) δ 8.16−8.15 (d, J = 7.7 Hz, 1 H),
8.01−8.00 (d, J = 4.2 Hz, 2 H), 7.95−7.92 (m, 1 H), 7.85−7.83 (d, J =
8.8 Hz, 2 H), 7.00−6.99 (d, J = 8.8 Hz, 2 H), 3.91 (s, 3 H). 13C NMR
(125 MHz, CDCl3) δ 165.2, 164.7, 158.0, 138.5, 136.3, 134.9, 132.8,
126.3, 125.8, 124.4, 121.2, 114.0, 55.7. MS = 317.0 (EI).
D
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Note
N-4-Trifluorobenzoylsaccharin (1c).18c Yield 83% (0.89 g). White
solid. 1H NMR (500 MHz, CDCl3) δ 8.17−8.15 (d, J = 7.7 Hz, 1 H),
8.06−8.05 (d, J = 4.0 Hz, 2 H), 7.99−7.95 (m, 1 H), 7.87−7.85 (d, J =
8.2 Hz, 2 H), 7.80−7.78 (d, J = 8.2 Hz, 2 H). 13C NMR (125 MHz,
CDCl3) δ 165.5, 157.2, 138.4, 136.8, 135.7, 135.1, 134.9 (q, J2 = 32.8
Hz), 129.6, 126.6, 125.5 (q, J3 = 3.7 Hz), 125.2, 123.4 (q, J1 = 271.2
Hz), 121.4. 19F NMR (471 MHz, CDCl3) δ −63.22. MS = 355.0 (EI).
N-4-Fluorobenzoylsaccharin (1d).18c Yield 79% (0.73 g). White
solid. 1H NMR (500 MHz, CDCl3) δ 8.17−8.15 (d, J = 7.7 Hz, 1 H),
8.04−8.03 (d, J = 3.9 Hz, 2 H), 7.97−7.94 (m, 1 H), 7.85−7.82 (t, J =
8.6 Hz, 2 H), 7.22−7.19 (t, J = 8.6 Hz, 2 H). 13C NMR (125 MHz,
CDCl3) δ 166.2 (d, J1 = 255.3 Hz), 165.2, 157.6, 138.4, 136.5, 135.0,
132.6 (d, J3 = 9.6 Hz), 128.6, 126.5, 125.5, 121.3, 115.9 (d, J2 = 22.3
Hz). 19F NMR (471 MHz, CDCl3) δ −102.58. MS = 305.0 (EI).
N-4-Chlorobenzoylsaccharin (1e).18c Yield 94% (0.91 g). White
solid. 1H NMR (500 MHz, CDCl3) δ 8.17−8.16 (d, J = 7.7 Hz, 1 H),
8.04−8.03 (d, J = 4.1 Hz, 2 H), 7.98−7.94 (m, 1 H), 7.74−7.73 (d, J =
8.3 Hz, 2 H), 7.51−7.50 (d, J = 8.4 Hz, 2 H). 13C NMR (125 MHz,
CDCl3) δ 165.4, 157.5, 140.6, 138.5, 136.6, 135.0, 131.9, 131.0, 128.9,
126.5, 125.4, 121.3. MS = 321.0 (EI).
workup and chromatography the title compound in 73% yield (34.2
mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =17.36 min. 1H
NMR (500 MHz, CDCl3) δ 7.68−7.65 (d, J = 16.0 Hz, 1 H), 7.51−
7.49 (d, J = 8.7 Hz, 2 H), 6.94−6.92 (d, J = 8.6 Hz, 2 H), 6.35−6.32
(d, J = 16.0 Hz, 1 H), 4.24−4.21 (t, J = 6.7 Hz, 2 H), 3.86 (s, 3 H),
1.74−1.68 (m, 2 H), 1.50−1.43 (m, 2 H), 1.00−0.97 (t, J = 7.4 Hz, 3
H). 13C NMR (125 MHz, CDCl3) δ 167.5, 161.3, 144.2, 129.7, 127.2,
115.8, 114.3, 64.3, 55.4, 30.8, 19.2, 13.8. MS = 234.1 (EI).
(E)-Butyl 3-(4-(Trifluoromethyl)phenyl)acrylate (3c).25 According
to the general procedure, the reaction of N-4-trifluoromethylbenzoyl-
saccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0
equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C,
afforded after workup and chromatography the title compound in 78%
yield (42.5 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt
1
=13.99 min. H NMR (500 MHz, CDCl3) δ 7.73−7.70 (d, J = 16.1
Hz, 1 H), 7.68−7.64 (t, J = 9.3 Hz, 4 H), 6.55−6.52 (d, J = 16.1 Hz, 1
H), 4.27−4.24 (t, J = 6.6 Hz, 2 H), 1.75−1.70 (m, 2 H), 1.51−1.43
(m, 2 H), 1.01−0.98 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz,
CDCl3) δ 166.5, 142.7, 137.9, 131.7 (q, J2 = 32.5 Hz), 128.2, 125.9 (q,
J3 = 3.7 Hz), 123.8 (q, J1 = 270.4 Hz), 120.9, 64.8, 30.7, 19.2, 13.8. 19
NMR (471 MHz, CDCl3) δ −62.86. MS = 272.1 (EI).
F
N-4-Bromobenzoylsaccharin (1f). New Compound. Yield 85%
(0.94 g). White solid. mp = 191−193 °C. 1H NMR (500 MHz,
CDCl3) δ 8.17−8.15 (d, J = 7.7 Hz, 1 H), 8.04−8.03 (d, J = 4.1 Hz, 2
H), 8.03−8.01 (d, J = 8.5 Hz, 1 H), 7.98−7.94 (m, 1 H), 7.71−7.70
(d, J = 8.3 Hz, 1 H), 7.69−7.64 (m, 2 H). 13C NMR (125 MHz,
CDCl3) δ 165.6, 157.4, 138.5, 136.6, 135.0, 132.4, 131.9, 131.0, 129.2,
126.5, 125.4, 121.3. MS = 364.9 (EI). HRMS calcd for C14H9BrO4NS
(M+ + H) 365.9430, found 365.9428.
(E)-Butyl 3-(4-Fluorophenyl)acrylate (3d).25 According to the
general procedure, the reaction of N-4-fluorobenzoylsaccharin (0.20
mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-
2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography the title compound in 69% yield (30.7 mg).
Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =14.74 min. 1H NMR
(500 MHz, CDCl3) δ 7.68−7.65 (d, J = 16.0 Hz, 1 H), 7.55−7.52 (t, J
= 7.5 Hz, 2 H), 7.12−7.08 (t, J = 8.3 Hz, 2 H), 6.40−6.37 (d, J = 16.0
Hz, 1 H), 4.25−4.22 (t, J = 6.6 Hz, 2 H), 1.74−1.68 (m, 2 H), 1.50−
1.43 (m, 2 H), 1.00−0.97 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz,
CDCl3) δ 167.0, 163.9 (d, J1 = 249.0 Hz), 143.3, 130.7, 129.9 (d, J3 =
8.5 Hz), 118.1 (d, J4 = 2.3 Hz), 116.0 (d, J2 = 21.7 Hz), 64.5, 30.8,
19.2, 13.8. 19F NMR (471 MHz, CDCl3) δ −109.78. MS = 222.1 (EI).
(E)-Butyl 3-(4-Chlorophenyl)acrylate (3e).25 According to the
general procedure, the reaction of N-4-chlorobenzoylsaccharin (0.20
mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-
2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography the title compound in 72% yield (34.4 mg).
Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =16.51 min. 1H NMR
(500 MHz, CDCl3) δ 7.66−7.63 (d, J = 16.0 Hz, 1 H), 7.49−7.47 (d, J
= 8.0 Hz, 2 H), 7.39−7.37 (d, J = 8.0 Hz, 2 H), 6.45−6.42 (d, J = 16.1
Hz, 1 H), 4.25−4.22 (t, J = 6.6 Hz, 2 H), 1.74−1.68 (m, 2 H), 1.50−
1.42 (m, 2 H), 1.00−0.97 (t, J = 7.3 Hz, 3 H). 13C NMR (125 MHz,
CDCl3) δ 166.9, 143.1, 136.1, 133.0, 129.2, 129.2, 118.9, 64.6, 30.8,
19.2, 13.8. MS = 238.1 (EI).
N-4-Methoxycarbonylbenzoylsaccharin (1g).18c Yield 91% (0.94
g). White solid. 1H NMR (500 MHz, CDCl3) δ 8.24−8.23 (d, J = 7.7
Hz, 1 H), 8.19−8.17 (d, J = 8.3 Hz, 2 H), 8.16−8.14 (d, J = 7.8 Hz, 1
H), 8.05−8.04 (d, J = 3.4 Hz, 2 H), 7.82−7.80 (d, J = 8.3 Hz, 2 H),
3.99 (s, 3 H). 13C NMR (125 MHz, CDCl3) δ 165.9, 157.2, 138.5,
136.6, 135.1, 134.4, 130.5, 130.1, 129.6, 129.2, 126.5, 125.3, 121.4,
52.6. MS = 345.0 (EI).
N-4-Nitrobenzoylsaccharin (1h).18c Yield 87% (0.87 g). White
solid. 1H NMR (500 MHz, CDCl3) δ 8.39−8.37 (d, J = 8.7 Hz, 2 H),
8.17−8.16 (d, J = 7.7 Hz, 1 H), 8.08−8.07 (d, J = 3.6 Hz, 2 H), 8.00−
7.97 (m, 1 H), 7.91−7.89 (d, J = 8.7 Hz, 2 H). 13C NMR (125 MHz,
CDCl3) δ 165.0, 162.6, 138.4, 137.9, 136.9, 135.2, 133.9, 130.1, 126.7,
125.0, 123.6, 121.5. MS = 332.0 (EI).
N-2-Fluorobenzoylsaccharin (1i).18c Yield 83% (0.76 g). White
solid. 1H NMR (500 MHz, CDCl3) δ 8.15−8.13 (d, J = 7.7 Hz, 1 H),
8.06−8.01 (m, 2 H), 7.96−7.93 (t, J = 6.7 Hz, 1 H), 7.72−7.69 (t, J =
7.5 Hz, 1 H), 7.65−7.61 (m, 1 H), 7.36−7.33 (t, J = 7.6 Hz, 1 H),
7.18−7.14 (t, J = 9.6 Hz, 1 H). 13C NMR (125 MHz, CDCl3) δ 162.5,
157.7 (d, J1 = 266.4 Hz), 138.5, 136.6, 134.8, 134.8, 130.7 (d, J3 = 1.5
Hz), 126.5, 125.2, 124.8, 124.7, 121.3, 115.9 (d, J2 = 21.2 Hz). 19F
NMR (471 MHz, CDCl3) δ −112.53. MS = 305.0 (EI).
(E)-Butyl 3-(4-Bromophenyl)acrylate (3f).25 According to the
general procedure, the reaction of N-4-bromobenzoylsaccharin (0.20
mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-
2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography the title compound in 63% yield (35.7 mg).
Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =17.36 min. 1H NMR
(500 MHz, CDCl3) δ 7.65−7.61 (d, J = 16.0 Hz, 1 H), 7.55−7.53 (d, J
= 8.2 Hz, 2 H), 7.42−7.40 (d, J = 8.3 Hz, 2 H), 6.47−6.43 (d, J = 16.0
Hz, 1 H), 4.25−4.22 (t, J = 6.6 Hz, 2 H), 1.74−1.68 (m, 2 H), 1.50−
1.42 (m, 2 H), 1.00−0.97 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz,
CDCl3) δ 166.9, 143.2, 133.4, 132.1, 129.4, 124.5, 119.0, 64.6, 30.8,
19.2, 13.8. MS = 282.0 (EI).
N-2-Methylbenzoylsaccharin (1j).18c Yield 95% (0.87 g). White
solid. 1H NMR (500 MHz, CDCl3) δ 8.10−8.09 (d, J = 7.7 Hz, 1 H),
8.04−8.00 (m, 2 H), 7.94−7.91 (t, J = 6.2 Hz, 1 H), 7.50−7.47 (t, J =
7.6 Hz, 1 H), 7.43−7.42 (d, J = 7.6 Hz, 1 H), 7.34−7.30 (m 2 H). 13C
NMR (125 MHz, CDCl3) δ 166.9, 156.8, 138.4, 136.6, 135.0, 133.1,
131.8, 130.9, 127.7, 126.4, 125.7, 125.3, 121.3, 19.39. MS = 301.0 (EI).
(E)-Butyl Cinnamate (3a).11 According to the general procedure,
the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol %) and
n-butyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for
18 h at 160 °C, afforded after workup and chromatography the title
compound in 82% yield (33.5 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z
> 98:2. GC: rt =15.46 min. 1H NMR (500 MHz, CDCl3) δ 7.72−7.69
(d, J = 16.0 Hz, 1 H), 7.56−7.55 (d, J = 4.9 Hz, 2 H), 7.41−7.40 (t, J =
1.9 Hz, 3 H), 6.49−6.45 (d, J = 15.9 Hz, 1 H), 4.25−4.23 (t, J = 6.6
Hz, 2 H), 1.75−1.69 (m, 2 H), 1.51−1.43 (m, 2 H), 1.01−0.98 (t, J =
7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.1, 144.6, 134.5,
130.2, 128.9, 128.1, 118.3, 64.5, 30.8, 19.2, 13.8. MS = 204.1 (EI).
(E)-Butyl 3-(4-methoxyphenyl)acrylate (3b).25 According to the
general procedure, the reaction of N-4-methoxylbenzoylsaccharin
(0.20 mmol), PdCl2 (3 mol%) and n-butyl acrylate (2.0 equiv) in N-
methyl-2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after
(E)-Methyl 4-(3-Butoxy-3-oxoprop-1-en-1-yl)benzoate (3g).25
According to the general procedure, the reaction of N-4-methox-
ycarbonylbenzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and n-butyl
acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at
160 °C, afforded after workup and chromatography the title
compound in 65% yield (34.1 mg). Colorless oil. 2,1/1,2 > 98:2. E/
1
Z > 98:2. GC: rt =18.66 min. H NMR (500 MHz, CDCl3) δ 8.08−
8.06 (d, J = 7.9 Hz, 2 H), 7.73−7.69 (d, J = 16.1 Hz, 1 H), 7.61−7.60
(d, J = 7.9 Hz, 2 H), 6.56−6.52 (d, J = 16.1 Hz, 1 H), 4.26−4.23 (t, J =
6.6 Hz, 2 H), 3.95 (s, 3 H), 1.74−1.69 (m, 2 H), 1.50−1.43 (m, 2 H),
1.00−0.97 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 166.6,
E
DOI: 10.1021/acs.joc.6b02294
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The Journal of Organic Chemistry
Note
166.5, 143.1, 138.7, 131.3, 130.1, 127.9, 120.7, 64.7, 52.3, 30.7, 19.2,
13.8. MS = 262.1 (EI).
16.7 Hz, 1 H). 13C NMR (125 MHz, CDCl3) δ 150.6, 133.5, 131.2,
129.1, 127.4, 118.2, 96.4. MS = 129.1 (EI).
(E)-Butyl 3-(4-Nitrophenyl)acrylate (3h).25 According to the
general procedure, the reaction of N-4-nitrobenzoylsaccharin (0.20
mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-
2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography the title compound in 77% yield (38.4 mg).
Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =18.78 min. 1H NMR
(500 MHz, CDCl3) δ 8.28−8.26 (d, J = 8.4 Hz, 2 H), 7.74−7.71 (d, J
= 17.4 Hz, 1 H), 7.71−7.69 (d, J = 8.9 Hz, 2 H), 6.60−6.57 (d, J =
16.0 Hz, 1 H), 4.27−4.25 (t, J = 6.6 Hz, 2 H), 1.75−1.70 (m, 2 H),
1.50−1.43 (m, 2 H), 1.01−0.98 (t, J = 7.5 Hz, 3 H). 13C NMR (125
MHz, CDCl3) δ 166.1, 148.5, 141.6, 140.6, 128.6, 124.2, 122.6, 64.9,
30.7, 19.2, 13.7. MS = 249.1 (EI).
(E)-Methyl 2-Methyl-3-phenyl Acrylate (3n).11 According to the
general procedure, the reaction of N-benzoylsaccharin (0.20 mmol),
PdCl2 (3 mol%), and n-butyl methacrylate (2.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and
chromatography the title compound in 78% yield (34.1 mg). Colorless
oil. Selectivity = 5.80:2.20:1.00. E/Z > 98:2. GC: rt = 15.01 min;
isomers 13.74, 13.61 min. The minor isomers could not be separated
1
by silica gel chromatography. Data for the major isomer. H NMR
(500 MHz, CDCl3) δ 7.71−7.42 (s, 1 H), 7.42−7.42 (d, J = 3.4 Hz, 4
H), 7.36−7.33 (m, 1 H), 4.26−4.23 (t, J = 6.6 Hz, 2 H), 2.14 (s, 3 H),
1.76−1.71 (m, 2 H), 1.52−1.44 (m, 2 H), 1.02−0.99 (t, J = 7.2 Hz, 3
H). 13C NMR (125 MHz, CDCl3) δ 168.8, 138.6, 136.0, 129.7, 129.0,
128.4, 128.2, 64.8, 30.8, 19.3, 14.1, 13.8. MS = 218.1 (EI).
(E)-Butyl 3-(4-Fluorophenyl)acrylate (3i).25 According to the
general procedure, the reaction of N-2-fluorobenzoylsaccharin (0.20
mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-
2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography the title compound in 91% yield (40.5 mg).
Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt =14.21 min. 1H NMR
(500 MHz, CDCl3) δ 7.85−7.82 (d, J = 16.2 Hz, 1 H), 7.58−7.55 (t, J
= 7.6 Hz, 1 H), 7.40−7.36 (m, 1 H), 7.20−7.17 (t, J = 7.6 Hz, 1 H),
7.14−7.10 (t, J = 9.8 Hz, 1 H), 6.58−6.55 (d, J = 16.2 Hz, 1 H), 4.26−
4.23 (t, J = 6.6 Hz, 2 H), 1.75−1.69 (m, 2 H), 1.50−1.43 (m, 2 H),
1.01−0.98 (t, J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.0,
161.4 (d, J1 = 252.3 Hz), 137.2, 131.6 (d, J4 = 8.7 Hz), 129.1 (d, J7 =
2.8 Hz), 124.4 (d, J6 = 3.6 Hz), 122.6 (d, J3 = 11.6 Hz), 120.9 (d, J5 =
6.5 Hz), 116.2 (d, J2 = 21.8 Hz), 64.6, 30.8, 19.2, 13.8. 19F NMR (471
MHz, CDCl3) δ −114.39. MS = 222.1 (EI).
(E)-5-Ethyl-1-phenylnon-1-en-3-one (3o).26 According to the
general procedure, the reaction of N-benzoylsaccharin (0.20 mmol),
PdCl2 (3 mol%), and 2-ethylhexyl acrylate (2.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and
chromatography the title compound in 75% yield (39.1 mg). Colorless
1
oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 18.02 min. H NMR (500
MHz, CDCl3) δ 7.72−7.69 (d, J = 16.0 Hz, 1 H), 7.56−7.55 (d, J = 4.9
Hz, 2 H), 7.41−7.41 (t, J = 3.2 Hz, 3 H), 6.49−6.46 (d, J = 16.0 Hz, 1
H), 4.16−4.14 (t, J = 5.1 Hz, 2 H), 1.70−1.66 (m, 1 H), 1.48−1.42
(m, 2 H), 1.38−1.34 (m, 6 H), 0.97−0.91 (m, 6 H). 13C NMR (125
MHz, CDCl3) δ 167.3, 144.5, 134.5, 130.2, 128.9, 128.1, 118.4, 67.0,
38.9, 30.5, 29.0, 23.9, 23.0, 14.1, 11.1. MS = 260.2 (EI).
(E)-Dec-1-en-1-ylbenzene (3p).11 Mixture of isomers. According to
the general procedure, N-benzoylsaccharin (0.20 mmol) was reacted
with PdCl2 (3 mol%), and 1-decene (2.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C. The compound was
(E)-Butyl 3-(o-Tolyl)acrylate (3j).25 According to the general
procedure, the reaction of N-2-methylbenzoylsaccharin (0.20 mmol),
PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and
chromatography the title compound in 97% yield (42.4 mg). Colorless
1
characterized by GC-MS analysis. The sample was analyzed by H
NMR (CDCl3, 500 MHz) and GC-MS to obtain conversion, yield and
selectivity using internal standard and comparison with authentic
samples. Yield =84%. Selectivity =8.44:2.72:5.99:1. GC: rt = 15.45
min; isomers 14.95, 14.51, 14.34 min. MS = 216.2 (EI). For
characterization data, see ref 11.
1
oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 15.15 min. H NMR (500
MHz, CDCl3) δ 8.02−7.98 (d, J = 15.9 Hz, 1 H), 7.59−7.57 (d, J = 7.7
Hz, 1 H), 7.31−7.28 (t, J = 7.2 Hz, 1 H), 7.25−7.22 (t, J = 6.9 Hz, 2
H), 6.40−6.37 (d, J = 15.9 Hz, 1 H), 4.26−4.23 (t, J = 6.7 Hz, 2 H),
2.47 (s, 3 H), 1.75−1.69 (m, 2 H), 1.51−1.43 (m, 2 H), 1.01−0.98 (t,
J = 7.4 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.2, 142.3, 137.6,
133.5, 130.8, 130.0, 126.4, 126.3, 119.3, 64.4, 30.8, 19.8, 19.2, 13.8. MS
= 218.1 (EI).
(E)-1,2-Diphenylethene (3q).11 According to the general procedure,
the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (5 mol%), and
styrene (3.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for 18 h at
160 °C, afforded after workup and chromatography the title
compound in 85% yield (30.6 mg). White solid. 2,1/1,2 = 90.9:9.1.
(E)-Methyl Cinnamate (3k).11 According to the general procedure,
the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and
methyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M) for
18 h at 160 °C, afforded after workup and chromatography the title
compound in 81% yield (26.3 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z
> 98:2. GC: rt = 12.56 min. 1H NMR (500 MHz, CDCl3) δ 7.74−7.71
(d, J = 16.0 Hz, 1 H), 7.55−7.55 (d, J = 2.9 Hz, 2 H), 7.42−7.41 (t, J =
2.5 Hz, 3 H), 6.49−6.46 (d, J = 16.0 Hz, 1 H), 3.84 (s, 3 H). 13C NMR
(125 MHz, CDCl3) δ 167.5, 144.9, 134.4, 130.3, 128.9, 128.1, 117.8,
51.7. MS = 162.1 (EI).
E/Z > 98:2. GC: rt = 15.58 min; isomer 13.81 min. H NMR (500
1
MHz, CDCl3) δ 7.56−7.54 (d, J = 7.7 Hz, 4 H), 7.41−7.38 (t, J = 7.7
Hz, 4 H), 7.31−7.28 (t, J = 7.1 Hz, 2 H), 7.14 (s, 2 H). 13C NMR (125
MHz, CDCl3) δ 137.4, 128.7, 128.7, 127.6, 126.5. MS = 180.1 (EI).
(E)-1-Chloro-4-styrylbenzene (3r).11 According to the general
procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2
(5 mol%), and 4-chlorostyrene (3.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography the title compound in 89% yield (38.2 mg).
White solid. 2,1/1,2 = 94.5:5.5. E/Z > 98:2. GC: rt = 16.92 min;
(E)-N-(tert-Butyl)cinnamamide (3l).11 According to the general
procedure, the reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (5
mol%), and N-(tert-butyl)acrylate (3.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography the title compound in 80% yield (32.6 mg).
isomer 14.72 min. H NMR (500 MHz, CDCl3) δ 7.54−7.53 (d, J =
1
7.7 Hz, 2 H), 7.48−7.46 (d, J = 8.1 Hz, 2 H), 7.41−7.38 (t, J = 7.7 Hz,
2 H), 7.36−7.35 (d, J = 8.2 Hz, 2 H), 7.32−7.29 (t, J = 6.8 Hz, 1 H),
7.13−7.06 (m, 2 H). 13C NMR (125 MHz, CDCl3) δ 137.0, 135.9,
133.2, 129.3, 128.9, 128.8, 127.9, 127.7, 127.4, 126.6. MS = 214.1 (EI).
(E)-1-Methoxy-4-styrylbenzene (3s).11 Method 1. According to the
general procedure, the reaction of N-benzoylsaccharin (0.20 mmol),
PdCl2 (5 mol%), and 4-methoxystyrene (3.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and
chromatography the title compound in 79% yield (33.2 mg). White
solid. 2,1/1,2 = 81.3:18.7. E/Z > 98:2. GC: rt = 17.67 min; isomer
15.53 min. 1H NMR (500 MHz, CDCl3) δ 7.53−7.51 (d, J = 7.8 Hz, 2
H), 7.49−7.48 (d, J = 8.3 Hz, 2 H), 7.39−7.36 (t, J = 7.6 Hz, 2 H),
7.28−7.25 (t, J = 8.0 Hz, 1 H), 7.11−6.99 (q, J = 16.3 Hz, 2 H), 6.94−
6.92 (d, J = 8.2 Hz, 2 H), 3.86 (s, 3 H). 13C NMR (125 MHz, CDCl3)
δ 159.3, 137.7, 130.2, 128.7, 128.2, 127.7, 127.2, 126.6, 126.3, 114.2,
55.4. MS = 210.1 (EI). Method 2. According to the general procedure,
the reaction of N-4-methoxylbenzoylsaccharin (0.20 mmol), PdCl2 (5
1
Colorless oil. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 16.60 min. H
NMR (500 MHz, CDCl3) δ 7.61−7.58 (d, J = 15.6 Hz, 1 H), 7.51−
7.50 (d, J = 7.0 Hz, 2 H), 7.40−7.37 (t, J = 6.6 Hz, 3 H), 6.36−6.33 (d,
J = 15.5 Hz, 1 H), 5.45 (s, 1 H), 1.46 (s, 9 H). 13C NMR (125 MHz,
CDCl3) δ 165.2, 140.3, 135.0, 129.5, 128.8, 127.7, 121.9, 51.5, 28.9.
MS = 203.1 (EI).
(E)-Cinnamonitrile (3m).11 According to the general procedure, the
reaction of N-benzoylsaccharin (0.20 mmol), PdCl2 (3 mol%), and
acrylonitrile (2.0 equiv) in N-methyl-2-pyrrolidinone (0.80 mL) for 18
h at 160 °C, afforded after workup and chromatography the title
compound in 95% yield (24.6 mg). Colorless oil. 2,1/1,2 > 98:2. E/Z
> 98:2. GC: rt = 12.35 min. 1H NMR (500 MHz, CDCl3) δ 7.49−7.45
(t, J = 11.2 Hz, 5 H), 7.43−7.42 (d, J = 8.2 Hz, 1 H), 5.93−5.90 (d, J =
F
DOI: 10.1021/acs.joc.6b02294
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The Journal of Organic Chemistry
Note
mol%), and styrene (3.0 equiv) in N-methyl-2-pyrrolidinone (0.25 M)
for 18 h at 160 °C, afforded after workup and chromatography the title
compound in 70% yield (29.4 mg). White solid. 2,1/1,2 = 74.6:25.4.
analyzed by 1H NMR (CDCl3, 500 MHz) and GC-MS to obtain
conversion and yield using internal standard and comparison with
authentic samples.
1
E/Z > 98:2. GC: rt = 17.74 min; isomer 15.58 min. H NMR (500
MHz, CDCl3) δ 7.53−7.51 (d, J = 7.8 Hz, 2 H), 7.49−7.48 (d, J = 8.3
Hz, 2 H), 7.39−7.36 (t, J = 7.6 Hz, 2 H), 7.28−7.25 (t, J = 8.0 Hz, 1
H), 7.11−6.99 (q, J = 16.3 Hz, 2 H), 6.94−6.92 (d, J = 8.2 Hz, 2 H),
3.86 (s, 3 H). 13C NMR (125 MHz, CDCl3) δ 159.3, 137.7, 130.2,
128.7, 128.2, 127.7, 127.2, 126.6, 126.3, 114.2, 55.4. MS = 210.1 (EI).
(E)-1-Styryl-4-(trifluoromethyl)benzene (3t).11 According to the
general procedure, the reaction of N-trifluoromethylbenzoylsaccharin
(0.20 mmol), PdCl2 (5 mol%), and styrene (3.0 equiv) in N-methyl-2-
pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup and
chromatography the title compound in 71% yield (35.2 mg). White
solid. 2,1/1,2 = 92.4:7.6. E/Z > 98:2. GC: rt = 14.66 min; isomer 12.34
min. 1H NMR (500 MHz, CDCl3) δ 7.63 (s, 4 H), 7.57−7.56 (d, J =
7.6 Hz, 2 H), 7.43−7.40 (t, J = 7.5 Hz, 2 H), 7.34−7.32 (t, J = 7.3 Hz,
1 H), 7.24−7.13 (q, J = 16.4 Hz, 2 H). 13C NMR (125 MHz, CDCl3)
δ 140.8, 136.6, 131.2, 129.3 (q, J2 = 32.5 Hz), 128.8, 128.3, 127.1,
126.8, 126.6, 125.7 (q, J3 = 3.6 Hz), 124.2 (q, J1 = 270.0 Hz). 19F
NMR (471 MHz, CDCl3) δ −62.45. MS = 248.1 (EI).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b02294.
■
S
1H and 13C NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Author
*michal.szostak@rutgers.edu
ORCID
Guangrong Meng: 0000-0002-3023-0654
Michal Szostak: 0000-0002-9650-9690
Notes
■
The authors declare no competing financial interest.
(E)-Butyl 3-(4-((E)-Styryl)phenyl)acrylate (3u).27 Method 1.
According to the published procedure,5d N-4-bromobenzoylsaccharin
(0.20 mmol) was reacted with Pd2(dba)3 (1.5 mol%), P(t-Bu)3HBF4
(3 mol%), Et3N (1.1 equiv), and styrene (2.0 equiv) in 1,4-dioxane
(0.25 M) for 12 h at room temperature. The reaction mixture was
filtrated, concentrated, and washed with hexanes (10 mL) to afford E-
(4-styryl)benzoyl-saccharine (97% yield, 75.6 mg). 2,1/1,2 > 98:2. E/Z
> 98:2. Without further purification, the thus obtained E-(4-
styryl)benzoylsaccharin (0.194 mmol) was reacted with PdCl2 (3
mol%) and n-butyl acrylate (2.0 equiv) in N-methyl-2-pyrrolidinone
(0.25 M) for 18 h at 160 °C to afford after workup and
chromatography the title compound (83% yield, 49.4 mg). White
solid. 2,1/1,2 > 98:2. E/Z > 98:2. GC: rt = 25.06 min. 1H NMR (500
MHz, CDCl3) δ 7.72−7.68 (d, J = 16.0 Hz, 1 H), 7.55 (s, 6 H), 7.41−
7.38 (t, J = 7.2 Hz, 2 H), 7.32−7.29 (t, J = 7.0 Hz, 1 H), 7.22−7.11 (q,
J = 16.4 Hz, 2 H), 6.49−6.46 (d, J = 16.0 Hz, 1 H), 4.26−4.23 (t, J =
6.5 Hz, 2 H), 1.75−1.70 (m, 2 H), 1.51−1.44 (m, 2 H), 1.01−0.98 (t, J
= 7.2 Hz, 3 H). 13C NMR (125 MHz, CDCl3) δ 167.2, 144.0, 139.3,
137.0, 133.7, 130.1, 128.8, 128.5, 128.0, 127.8, 126.9, 126.7, 117.9,
64.5, 30.8, 19.2, 13.8. MS = 306.2 (EI). Method 2. According to the
general procedure, the reaction of N-4-bromobenzoylsaccharin (0.20
mmol), PdCl2 (3 mol%), and n-butyl acrylate (2.0 equiv) in N-methyl-
2-pyrrolidinone (0.25 M) for 18 h at 160 °C, afforded after workup
and chromatography n-butyl E-(4-bromophenyl)acrylate (63% yield,
35.7 mg). The thus obtained n-butyl E-(4-bromophenyl)acrylate
(0.126 mmol) was reacted with Pd2(dba)3 (1.5 mol%), P(t-Bu)3HBF4
(3 mol%), Et3N (1.1 equiv), and styrene (2.0 equiv) in 1,4-dioxane
(0.25 M) for 12 h at room temperature according to the previously
published procedure.5d The reaction mixture was filtered, concen-
trated, and washed with hexanes (10 mL) to afforded the title
compound (98% yield, 37.9 mg). White solid. 2,1/1,2 > 98:2. E/Z >
ACKNOWLEDGMENTS
■
Financial support was provided by Rutgers University. The 500
MHz spectrometer used in this study was supported by the
NSF-MRI grant (CHE-1229030).
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