Regioselective 1,2-addition of allenamides with: N -haloimides: Synthesis of 2-halo allylic aminal derivatives

Article abstract of DOI:10.1039/c7ob00882a

A strategy for the synthesis of 2-halo allylic aminal derivatives through regioselective 1,2-addition of allenamides with N-haloimides is presented. This reaction was conducted under very mild conditions and gave up to 99% yield. Moreover, the obtained ha

Full text of DOI:10.1039/c7ob00882a

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ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Regioselective 1,2-additon of allenamides with N-haloimides:
synthesis of 2-halo allylic aminal derivatives
Hong-He Li, Xiao-Xiao Li*, Zhi-Gang Zhao*, Xiao Yuan and Chen-Yang Sun
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A strategy for the synthesis of 2-halo allylic aminal derivatives through regioselective 1,2-addition of allenamides with N-
haloimides is presented. This reaction was conducted under very mild conditions and gave up to 99% yield. Moreover, the
obtained halides allow functional group diversification by palladium-catalyzed coupling reactions, which could act as
potential intermediates for the synthesis of valuable compounds.
www.rsc.org/
(a) previous work
N
Introduction
N
Ph
N
NIS
.
N
Protected aminals have been incorporated into peptide chains,
and the resulting structures provide the so-called retro-inverso
mimics.1 Additionally, various core chiral aminal subunits could
be found in natural products2 and pharmaceuticals.3 Moreover,
aminals have also been involved as partners in transition
metal-catalyzed reaction through C−N bond acꢀvaꢀon.4
Because of the importance of structural entity, the
development of new strategies to construct aminal derivatives
has attracted much synthetic effort.
+
N
H
Ph
CH3CN, r t
Ts
N
Ts
I
(b) this work:
O
R1
Reaction
Condition
.
N
R2
+
N
X
O
O
X
N
R1
O
N
R2
To the best of our knowledge, the addition of amide
nucleophiles to doubly activated imines,5 or catalytic addition
of amides to imines6 has been a popular area of study for the
synthesis of aminal derivatives. The regio- and stereo-
controlled functionalization of carbon-carbon double bonds
has enormous potential in organic synthesis.7 Among them,
allenamides have recently proven to be important synthetic
Scheme 1 Synthesis of 2-halo allylic aminal derivatives.
synthesized through NIS-madiated intermolecular nucleophilic
addition of imidazole and allenamide involved 1,2-addition
pathway (Scheme 1a).14 Encouraged by these achievements
and continuing our interest in the halogen mediated reactions
of allenamides, we envisioned that N-haloimides could be
served as both electrophiles and nucleophiles without extra
nucleophilic agents to synthesize 2-halo allylic aminal
derivatives through 1,2-addition pathway (Scheme 1b).
intermediates,
transformations.8 As
undergoing
diverse
interesting
a
new approach to synthesis this
structural entity, Broggini and Baäckvall group reported the
transition metal-catalyzed intramolecular hydroamination9 or
carboamination10 of allenamides to produce cyclo-aminal
derivatives. Broggini also found that base could promoted this
transformation.11 However, the utility of this preparation was
limited to the intramolecular cyclization of allenamides,.
Intermolecular hydroamination of allenamides to synthesis
aminal derivatives was seldom reported due to the
regioselectivity for the 1,4-addition pathway.12
Results and discussion
With this idea in mind, we examined the reaction of benzyl
substituted allenamide
(
1a)
with 1.2 equiv of N-
chlorosuccinimide (2a) in DCM at room temperature. The
optimization results are summarized in Table 1. The desired
1,2-addition product 3aa was isolated in 50% yield after 4 h,
along with significant amounts of degradation product 4-
methyl-N-phenylbenzenesulfonamide (Table 1, entry 1). An
increase in the amount of N-chlorosuccinimide to 2.0 equiv
afforded 3aa in 51% yield after 1 h and the yield of 3aa
equaled 51% on increasing the amount of N-chlorosuccinimide
to 3 equiv (Table 1, entries 2-3). Moreover, the reaction time
was shortened to 0.5 h when the amount of 1a increased to
1.1 equiv, though the yield of 3aa was also equaled 51% (Table
Our research group has focused on the reactions of
allenamides,13 and we found that 2-halo allylic aminal could be
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1, entry 4). Subsequent screening of the solvents led to an
increase in the yield to 67% when CH3Cl and CCl4 were used as
the solvent, whereas DCE, CH3CN, toluene, and benzene were
not as effective. Notably, Only 20% yield of 3aa was obtained
when CH3CN was used because of the poor solubility of the 2a
.
The yield was higher in the solvent with high polarity,
providing the evidence of the ion pair mechanism. The N-
haloimides
bromosuccinimide (2b) and N-iodosuccinimide (2c) could give
3ab and 3ac in 82% and 85% yield, N-chlorophthalimide (2d
exhibited better reactivity, giving 3ad in 99% yield (Table 1,
entries 11−13). When N-bromophthalimide 2e and N-
were
then
evaluated.
Whereas
N-
)
(
)
iodophthalimide (2f) were used in this reaction, the 1,2-
addition products 3ae and 3af were isolated in 88% and 43%
yield, respectively (Table 1, entries 14−15). At the meanꢀme,
the 1,4-addition products 4ae and 4af could also obtained in
10% and 14% yield,15 providing the evidence of the reaction
mechanism. The molecular structure of the selective 1,2-
Figure 1 X-ray structure of compound 3aa
.
addition product was determined by the single-crystal
diffraction study of 3aa (Figure 1).16
After having established the optimized conditions for the
present reaction, various allenamide derivatives were
subjected to the above conditions, as summarized in Table 2.
4-F- or 4-MeO-substituted benzyl allenamides were suitable
for accessing 2-chloro allylic aminal derivatives 3bd and 3cd in
99% and 92% yield in the presence of N-chlorophthalimide
Table 1 Screening of the optimal conditions.a
(
2d). Phenyl allenamide 1d also provided the desired product
3dd in 98% yield. Subsequently, the substitution effect on the
aryl ring of phenyl allenamide was examined. At first, several
para-substituted phenyl allenamides were investigated. The
reactions of substrates 1e and 1f both bearing an electron
donating-group at the para position of the aromatic ring
resulted in the corresponding products 3ed and 3fd in 90%
O
.
Reaction
Condition
N
O
O
X
+
N X
N
Ts
N
O
Ts
1a
2
3aa-3af
yield. The yields of 3jd, 3hd and 3id increased with an increase
O
O
in electronegativity of substituents at the para positions of the
aromatic rings. 2-F-substituted phenyl allenamide 1j could also
give the corresponding product 3jd in 91% yield. Subsequently,
substrates 1k-1m with different substituent at the meta
positions of the aromatic rings were designed. The
2a
2b, X= Br
2c, X= I
2d
, X = Cl
2e, X= Br
2f, X= I
, X = Cl
N
X
N X
O
O
Entrya)
2
1a/2
Solvent
Time
(h)
4
Yield of
3
(%)b
corresponding products 3kd−3md were obtained in good
yields. In the meantime, the reaction also worked well with the
substrates 1n which had two substituents on the same aryl
group, furnishing the expected products 3nd in 77% yield.
Furthermore, the reactivity of different aliphatic substituted
allenamides was also investigated. Both phenethyl and n-butyl
substituted allenamides produced products 3od and 3pd in 98%
yield, respectively. The reaction was also efficient with
allenamides when mesyl and acyl were used in the place of
tosyl as the amino protecting group. Thus, the reaction of
phenyl allenamide 1q with a mesyl substituent afforded 3qd in
98% yield, 1r with an acyl substituent furnished 3rd in 91%
yield, 2-oxazolidinone allenamide 1s also provided the
corresponding adduct 3sd in 92% yield. For the allenamides
with phenyl and dimethyl in the allene, the corresponding
products 3td and 3ud were both obtained in 98% yield.
1
2a 1/1.2 DCM
3aa (50)
2
2a 1/2
2a 1/3
DCM
DCM
1
3aa (51)
3aa (51)
3aa (51)
3aa (47)
3aa (67)
3aa (67)
3aa (20)
3aa (63)
3aa (65)
3ab (82)
3ac (85)
3ad (99)
3ae (88)
3af (43)
3
1
4
2a 1.1/1 DCM
2a 1.1/1 DCE
2a 1.1/1 CHCl3
2a 1.1/1 CCl4
2a 1.1/1 CH3CN
2a 1.1/1 Toluene
2a 1.1/1 Benzene
2b 1.1/1 CHCl3
0.5
1
5
6
1
7
2.5
1
8
9
3
10
11
12
13
14c
15d
3
1
2c
1.1/1 CHCl3
1
2d 1.1/1 CHCl3
2e 1.1/1 CHCl3
1
1
2f
1.1/1 CHCl3
1
On the basis of our experimental results and precedents in
the literature,17 we propose a mechanism for the reaction as
shown in Scheme 2. The reaction of 1a and N-haloimide leads
aUnless otherwise noted, all reactions were carried out at 0.11
mmol of 1a and 0.1 mmol of 2 in 3 mL solvent at room
temperature. bYield of isolated product. c10% yield of 1,4-
d
addition product 4ae was isolated. 14% yield of 1,4-addition
initially to an ion pair 5 composed of an σ-complex and the
conjugate base of the imide. Subsequently, the mutual
attraction between the σ-complex sulfimide ion species and
product 4af was isolated.
2 | J. Name., 2012, 00, 1-3
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the conjugate base promoted the 1,2-addition pathway to give
2-halo allylic aminal derivatives . The formation of 1,4-
3
addition product 4ae and 4af could also indicate that the σ-
complex is the conjugated sulfimide ion species.
Table 2 Substrate scopea,b
O
O
O
O
N
N
O
O
O
O
O
O
N
N
N
Cl
Cl
Cl
Cl
Cl
N
N
N
Me
N
MeO
N
Ts
Ts
Ts
Ts
Ts
F
MeO
3bd
3cd
3dd
3ed
, 90% yield
3fd
, 90% yield
, 99% yield
, 92% yield
, 98% yield
O
F
O
O
N
O
N
O
N
O
O
N
O
O
N
O
Cl
Cl
Cl
Cl
Cl
N
N
F
N
Cl
N
Br
N
Ts
Ts
Ts
Ts
Ts
F
3gd
3hd
3id
, 95% yield
3jd
, 91% yield
3kd
, 93% yield
, 99% yield
, 98% yield
O
N
O
O
N
O
O
N
O
MeO
O
N
O
O
N
O
Cl
Cl
Cl
Cl
Cl
N
N
N
N
N
Ts
Ts
Ts
Ts
Ts
Br
MeO
3md
MeO
3nd
3ld
3od
3pd
, 98% yield
, 92% yield
, 86% yield
, 77% yield
, 98% yield
O
O
N
O
O
N
O
N
O
O
N
O
O
O
N
Cl
N
Cl
N
Cl
Cl
Cl
N
N
N
Ts
Ms
O
Ts
Ac
O
3qd
, 99% yield
3rd
, 91% yield
3sd
3td,
3ud,
yild, 98%
, 92% yield
yild, 98%
aReaction conditions: 1 (0.11 mmol), 2d (0.1 mmol), CHCl3 (3 mL), r t. bYield of isolated product.
To prove the practicality of this reaction, a gram-scale
synthesis of the 2-chloro allylic aminal 3ad was performed
When 1.65 g of allenamide 1a (5.5 mmol) was used, 2.35 g of
the desired product 3ad was obtained in 98% yield within 1 h,
indicating that this transformation is easy to scale up to the
gram scale without loss in efficiency (Scheme 3). To further
demonstrate the potential application of this protocol, 3ac
and 3ae were reacted with phenylacetylene under
Sonagashira cross-coupling conditions,18 the corresponding
coupling products 6ac and 6ae were isolated in 83% and 84%
yield, respectively.
Conclusions
In conclusion, a new and mild protocol for the synthesis of 2-
halo allylic aminal derivatives has been established. The N-
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haloimides were served as both electrophiles and
nucleophiles in this reaction. The resulting 2-halo allylic
aminals are readily elaborated to more products by using
known organopalladium chemistry, which may be essential
intermediates for building delicate and sophisticated natural
products. The potential utilization and extension of this
interesting synthetic methodology are currently underway.
Scheme 2 Proposed reaction mechanism.
Scheme 3 Gram-scale synthesis and synthetic application.
reaction components. Melting points were determined from the
solids obtained from column chromatography using a WRS-1B
digital melting point instrument. IR spectra were recorded on a
Nicoletisso FTIR spectrometer using KBr disks. Unless otherwise
noted, nuclear magnetic resonance spectra were recorded at
room temperature on an Agilent 400 MHz spectrometer using
CDCl3 as the solvent and TMS as the internal reference. Chemical
shifts for 13C NMR spectra were recorded in parts per million
relative to tetramethylsilane using the central peak of
deuterochloroform (77.0 ppm) as the internal standard. HRMS
Experimental
General information
All reactions were conducted under open air at room temperature.
THF、toluene and DCM、DCE、CHCl3 were freshly distilled over
sodium/benzophenone and calcium hydride, respectively.
Commercial reagents were used as supplied or were purified by
standard techniques where necessary. Column chromatography
was performed using Qingdao Haiyang Chemical Co., Ltd silica gel
(200–300 mesh) with the appropriate solvent system, as
determined by TLC analysis (Qingdao Haiyang Chemical Co., Ltd,
silica gel F254) using UV light and KMnO4 stain to visualize the
was performed using
a Bruker Daltonics Bio TOF mass
spectrometer. N-haloimides 2a-2e were obtained commercially
4 | J. Name., 2012, 00, 1-3
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and used without further purification. N-iodophthalimide 2f was
prepared according to the published method.19
N-benzyl-N-(2-bromo-1-(2,5-dioxopyrrolidin-1-yl)allyl)-4-
methylbenzenesulfonamide (3ab). White solid (39.1 mg,
82%). M p 146-147℃
. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J =
General procedure for allenamides 1a-1t synthesis via base-
induced isomerizations.20
8.1 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.12 – 7.10 (m, 3H), 6.79
(d, J = 5.8 Hz, 2H), 6.73 (s, 1H), 5.94 (s, 1H), 5.82 (s, 1H), 5.02
(d, J = 17.7 Hz, 1H), 4.59 (d, J = 17.7 Hz, 1H), 2.43 (s, 3H), 2.12
– 1.93 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 175.32, 144.18,
136.93, 136.74, 129.68, 128.07, 127.83, 127.03, 126.09,
124.67, 120.31, 67.07, 48.39, 27.43, 21.56. IR (neat) 3041,
2934, 2861, 1499, 1454, 758, 545 cm-1. HRMS (ESI) calcd for
C21H21BrN2O4SNa [M+Na]+ 499.0298; found: 499.0298.
To a solution of N-tosyl propargylamine (5.0 mmol, 1.0 equiv)
in 15 ml of anhydrous THF under N2 atmosphere at 0
℃ was
added in portions 169 mg of tBuOK (30 mol%, 1,5 mmol). The
reaction was allowed to stir at room temperature. After 12 h
the mixture was diluted with 10 mL of Et2O, and then filtrated
over celite. The residue was washed with diethyl ether. The
collected filtrate was concentrated in vacuo and the residue
purified by flash column chromatography on silica gel
(gradient eluent: EtOAc in hexane), affording the desired N-
tosylallenamides.
N-benzyl-N-(1-(2,5-dioxopyrrolidin-1-yl)-2-iodoallyl)-4-
methylbenzenesulfonamide (3ac). White solid (44.3 mg,
85%). M p 129-131
℃
. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J =
N-benzyl-4-methyl-N-(3-phenylpropa-1,2-dien-1-
7.8 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 7.11 – 7.09 (m, 3H), 6.77
(d, J = 6.9 Hz, 2H), 6.69 (s, 1H), 6.36 (s, 1H), 6.07 (s, 1H), 5.02
(d, J = 17.7 Hz, 1H), 4.58 (d, J = 17.7 Hz, 1H), 2.43 (s, 3H), 2.08
– 1.92 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 175.27, 144.11,
136.86, 136.55, 129.64, 128.57, 128.02, 127.77, 126.98,
126.05, 101.30, 69.60, 48.39, 27.38, 21.53. IR (neat) 3041,
2934, 2861, 1499, 1457, 758, 545 cm-1. HRMS (ESI) calcd for
C21H21IN2O4SNa [M+Na]+ 547.0159; found: 547.0151.
yl)benzenesulfonamide (1t). White solid (1125 mg, 60%). M p
1
. H NMR (400 MHz, DMSO) δ 7.86 (d, J = 8.1 Hz,
111-112℃
2H), 7.51 (d, J = 7.9 Hz, 2H), 7.25 – 7.11 (m, 9H), 6.81 (d, J =
7.1 Hz, 2H), 6.67 (d, J = 5.9 Hz, 1H), 4.28 (s, 2H), 2.46 (s, 3H).
13C NMR (100 MHz, DMSO) δ 197.05, 144.20, 136.00, 133.14,
130.12, 128.36, 128.31, 127.92, 127.56, 127.36, 127.24,
127.18, 127.04, 105.78, 102.83, 49.86, 21.10. IR (neat) 3040,
2934, 2863, 1498, 1450, 758, 699, 545 cm-1. HRMS (ESI) calcd
for C21H21NO2SNa [M+Na]+ 386.1191; found: 386.1192.
General procedure for allenamide 1u synthesis via Cu (I)
catalysed cross-coupling.21
N-benzyl-N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-4-
methylbenzenesulfonamide (3ad). White solid (47.6 mg,
99%). M p 126-127
℃
. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
8.0 Hz, 2H), 7.61 (s, 4H), 7.23 (d, J = 8.0 Hz, 2H), 6.92 (s, 1H),
6.82 – 6.75 (m, 4H), 6.72 – 6.70 (m, 1H), 5.66 – 5.65 (m, 2H),
5.03 (d, J = 17.3 Hz, 1H), 4.73 (d, J = 17.4 Hz, 1H), 2.38 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 166.55, 143.86, 137.15, 136.20,
134.42, 134.10, 130.77, 129.54, 127.76, 127.67, 126.36,
123.36, 116.41, 65.92, 48.94, 21.51. IR (neat) 3038, 2934,
2861, 1499, 1454, 758, 700, 545 cm-1. HRMS (ESI) calcd for
C25H21ClN2O4SNa [M+Na]+ 503.0803; found: 503.0801.
A solution of amide (1.2 equiv), CuCN (10 mol%), Cs2CO3 (2.0
equiv), N, N’-dimethylethylenediamine (20 mol%) and allenyl
iodide (1 equiv) in toluene (0.1 M) was heated to 50 °C for 18
h before being cooled to rt. After filtration through CeliteTM,
the filtrate was concentrated under reduced pressure.
Separation and purification of the resulting crude residue via
silica gel flash column chromatography (hexane/EtOAc = 4/1)
afforded the desired allenamide 1u in 30% yield.
N-benzyl-N-(2-bromo-1-(1,3-dioxoisoindolin-2-yl)allyl)-4-
methylbenzenesulfonamide (3ae). White solid (45.8 mg,
General procedure for selective 1, 2-additon of allenamide
1a with N-chlorophthalimide 2d.
88%). M p 130-132
℃
. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
To a suspension of 1a (0.11 mmol) in CHCl3 (3 mL) was added
2d (0.1 mmol) in one portion. Then the reaction mixture was
8.0 Hz, 2H), 7.64 – 7.57 (m, 4H), 7.23 (d, J = 8.0 Hz, 2H), 6.95
(s, 1H), 6.80 – 6.68 (m, 5H), 6.06 (s, 1H), 5.88 (s, 1H), 5.03 (d, J
= 17.3 Hz, 1H), 4.73 (d, J = 17.3 Hz, 1H), 2.38 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 166.49, 143.87, 137.19, 136.14, 134.09,
130.79, 129.55, 127.77, 127.72, 126.36, 125.46, 123.39,
120.70, 109.99, 67.26, 48.91, 21.53. IR (neat) 3041, 2934,
2861, 1499, 1454, 758, 702, 545 cm-1. HRMS (ESI) calcd for
C25H21BrN2O4SNa [M+Na]+ 547.0298; found: 547.0293.
stirred at room temperature for
1 h until complete
consumption of starting material as monitored by TLC.
Concentration of the reaction mixture in vacuo followed by
purification through flash chromatography on silica gel
column (hexane/EtOAc = 5/1 as the eluent) afforded 3ad
(47.6 mg, 99% yield) as a white solid.
N-benzyl-N-(2-chloro-1-(2,5-dioxopyrrolidin-1-yl)allyl)-4-
methylbenzenesulfonamide (3aa). White solid (29.0 mg,
(Z)-N-benzyl-N-(2-bromo-3-(1,3-dioxoisoindolin-2-yl)prop-1-
en-1-yl)-4-methylbenzenesulfonamide (4ae)
.
White solid
1
(5.2 mg, 10%). M p 157-158℃. H NMR (400 MHz, CDCl3) δ
67%). M p 148-149
℃
. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J =
8.2 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.12 – 7.10 (m, 3H), 6.80
(brs, 2H), 6.71 (s, 1H), 5.61 – 5.60 (m, 1H), 5.54 – 5.52 (m, 1H),
5.03 (d, J = 17.6 Hz, 1H), 4.59 (d, J = 17.7 Hz, 1H), 2.44 (s, 3H),
2.09 – 1.93 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 175.42,
144.20, 136.94, 136.82, 133.68, 129.69, 128.08, 127.83,
127.05, 126.09, 116.01, 65.76, 48.38, 27.44, 21.58. IR (neat)
3038, 2934, 2861, 1501, 1454, 758, 702, 545 cm-1. HRMS (ESI)
calcd for C21H21ClN2O4SNa [M+Na]+ 455.0803; found:
455.0800.
7.87 – 7.84 (m, 2H), 7.79 – 7.70 (m, 4H), 7.29 (d, J = 8.1 Hz,
2H), 7.25 (brs, 2H), 7.23 – 7.17 (m, 3H), 6.63 (s, 1H), 4.62 (s,
2H), 4.47 (s, 2H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
167.07, 143.83, 135.82, 135.36, 134.16, 131.74, 129.66,
129.01, 128.58, 128.26, 127.70, 127.50, 123.48, 120.61, 52.34,
44.00, 21.55. IR(neat) 3038, 2934, 2861, 1496, 1459, 758, 702,
542 cm-1. C25H21BrN2O4SNa [M+Na]+ 547.0298; found:
547.0297.
N-benzyl-N-(1-(1,3-dioxoisoindolin-2-yl)-2-iodoallyl)-4-
methylbenzenesulfonamide (3af). White solid (24.5 mg, 43%).
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. H NMR (400 MHz, CDCl3) δ 7.73 – 7.69 (m,
M p 150-151
℃
. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.4 Hz,
M p 157-158
℃
2H), 7.60 (brs, 4H), 7.23 (d, J = 7.7 Hz, 2H), 6.90 (s, 1H), 6.78 –
6.71 (m, 4H), 6.69 – 6.67 (m, 1H), 6.48 (s, 1H), 6.13 (s, 1H),
5.02 (d, J = 17.3 Hz, 1H), 4.71 (d, J = 17.4 Hz, 1H), 2.38 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 166.40, 143.82, 137.11, 135.96,
134.08, 130.68, 129.53, 128.92, 127.72, 127.67, 126.28,
123.37, 102.11, 69.82, 48.86, 21.50. IR(neat) 3041, 2934,
2861, 1499, 1454, 758, 702, 545 cm-1. HRMS (ESI) calcd for
C25H21IN2O4SNa [M+Na]+ 595.0159; found: 595.0151.
4H), 7.66 (d, J = 8.1 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 7.02 (s,
1H), 6.89 (d, J = 7.7 Hz, 2H), 6.75 (brs, 2H), 6.45 (s, 1H), 5.85 (s,
1H), 2.40 (s, 3H), 2.23 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
165.92, 143.89, 139.45, 135.99, 135.78, 134.43, 131.99,
131.86, 130.88, 129.62, 129.23, 128.37, 123.76, 116.89, 67.08,
21.59, 21.17. IR (neat) 3041, 2934, 2861, 1499, 1454, 758,
700, 545 cm-1. HRMS (ESI) calcd for C25H21ClN2O4SNa [M+Na]+
503.0803; found: 503.0798.
(Z)-N-benzyl-N-(3-(1,3-dioxoisoindolin-2-yl)-2-iodoprop-1-
en-1-yl)-4-methylbenzenesulfonamide (4af). White solid (8
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(4-
methoxyphenyl)-4-methylbenzenesulfonamide (3fd). White
solid (44.5 mg, 90%). M p 79-80℃
. 1H NMR (400 MHz, CDCl3)
mg, 14%). M p 153-154
℃
. 1H NMR (400 MHz, CDCl3) δ 7.87 –
7.85 (m, 2H), 7.78 – 7.73 (m, 4H), 7.33 – 7.27 (m, 4H), 7.25 –
7.17 (m, 3H), 6.38 (s, 1H), 4.54 (s, 2H), 4.50 (s, 2H), 2.42 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 167.07, 143.89, 135.54,
134.95, 134.73, 134.19, 131.76, 129.68, 129.24, 128.27,
127.84, 127.79, 123.53, 103.67, 53.41, 46.79, 21.58. IR(neat)
3037, 2934, 2863, 1495, 1459, 760, 702, 542 cm-1. HRMS (ESI)
calcd for C25H21IN2O4SNa [M+Na]+ 595.0159; found: 595.0163.
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(4-
δ 7.76 – 7.67 (m, 4H), 7.65 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0
Hz, 2H), 7.01 (s, 1H), 6.76 (brs, 2H), 6.59 (d, J = 7.8 Hz, 2H),
6.43 (s, 1H), 5.84 (s, 1H), 3.71 (s, 3H), 2.40 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 165.93, 159.84, 143.91, 136.07, 135.72,
134.45, 133.43, 130.87, 129.26, 128.37, 126.85, 123.79,
116.81, 114.07, 67.12, 55.25, 21.60. IR (neat) 3041, 2934,
2861, 1499, 1454, 758, 700, 545 cm-1. HRMS (ESI) calcd for
C25H21ClN2O5SNa [M+Na]+ 519.0752; found: 519.0750.
fluorobenzyl)-4-methylbenzenesulfonamide (3bd)
.
White
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(4-
solid (49.1 mg, 99%). M p 134-135
℃.
1H NMR (400 MHz,
fluorophenyl)-4-methylbenzenesulfonamide (3gd). White
solid (47.5 mg, 99%). M p 154-155℃.
1H NMR (400 MHz,
CDCl3) δ 7.74 (d, J = 8.1 Hz, 2H), 7.66 (brs, 4H), 7.22 (d, J = 7.9
Hz, 2H), 6.90 (s, 1H), 6.85 – 6.77 (m, 2H), 6.52 (t, J = 8.6 Hz,
2H), 5.63 (s, 1H), 5.58 (s, 1H), 4.97 (d, J = 17.1 Hz, 1H), 4.72 (d,
J = 17.1 Hz, 1H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
166.57, 161.43 (d, J = 245.9 Hz), 144.01, 137.03, 134.35,
134.30, 132.03 (d, J = 3.1 Hz), 130.73, 129.57, 128.27 (d, J =
8.1 Hz), 127.60, 123.46, 116.56, 114.59 (d, J = 21.5 Hz), 66.03,
48.45, 21.50. IR (neat) 3041, 2934, 2861, 1499, 1454, 758,
700, 545 cm-1. HRMS (ESI) calcd for C25H20ClFN2O4SNa
[M+Na]+ 521.0709; found: 521.0708.
CDCl3) δ 7.77 – 7.69 (m, 4H), 7.65 (d, J = 8.0 Hz, 2H), 7.24 (d, J
= 8.1 Hz, 2H), 7.02 (s, 1H), 6.87 (brs, 2H), 6.80 (t, J = 8.1 Hz,
2H), 6.38 (s, 1H), 5.84 (s, 1H), 2.40 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 165.92, 162.69 (d, J = 250.4 Hz), 144.24, 135.85,
135.43, 134.61, 134.25 (d, J = 11.1 Hz), 130.76, 130.63 (d, J =
3.3 Hz), 129.41, 128.32, 123.87, 116.98, 116.00 (d, J = 22.8
Hz), 67.12, 21.61. IR (neat) 3038, 2934, 2861, 1496, 1451,758,
545 cm-1. HRMS (ESI) calcd for C24H18ClFN2O4SNa [M+Na]+
507.0552; found: 507.0551.
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(4-
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(4-
methoxybenzyl)-4-methylbenzenesulfonamide (3cd). White
1H NMR (400 MHz,
chlorophenyl)-4-methylbenzenesulfonamide (3hd). White
solid (49.0 mg, 98%). M p 136-137℃.
1H NMR (400 MHz,
solid (47.1 mg, 92%). M p 172-173
℃.
CDCl3) δ 7.75 (d, J = 7.9 Hz, 2H), 7.63 (brs, 4H), 7.23 (d, J = 7.9
Hz, 2H), 6.89 (s, 1H), 6.70 (d, J = 8.2 Hz, 2H), 6.32 (d, J = 8.3 Hz,
2H), 5.64 (d, J = 8.5 Hz, 2H), 4.96 (d, J = 17.0 Hz, 1H), 4.64 (d, J
= 17.0 Hz, 1H), 3.48 (s, 3H), 2.38 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 166.56, 158.14, 143.76, 137.22, 134.45, 134.02,
130.89, 129.49, 128.09, 127.84, 127.65, 123.37, 116.38,
113.17, 65.91, 54.96, 48.45, 21.50. IR (neat) 3038, 2934, 2861,
1499, 1454, 758, 545 cm-1. HRMS (ESI) calcd for
C26H23ClN2O5SNa [M+Na]+ 533.0908; found: 533.0908.
CDCl3) δ 7.78 – 7.71 (m, 4H), 7.65 (d, J = 8.1 Hz, 2H), 7.24 (d, J
= 8.0 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H), 7.01 (s, 1H), 6.84 (d, J =
7.7 Hz, 2H), 6.36 (s, 1H), 5.83 (s, 1H), 2.41 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 165.94, 144.30, 135.76, 135.59, 135.41,
134.64, 133.63, 133.38, 130.78, 129.45, 129.22, 128.32,
123.93, 117.11, 67.14, 21.63. IR (neat) 3038, 2934, 2861,
1499, 1451, 758, 542 cm-1. HRMS (ESI) calcd for
C24H18Cl2N2O4SNa [M+Na]+ 523.0257; found: 523.0256.
N-(4-bromophenyl)-N-(2-chloro-1-(1,3-dioxoisoindolin-2-
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-4-methyl-N-
phenylbenzenesulfonamide (3dd). White solid (45.8 mg,
yl)allyl)-4-methylbenzenesulfonamide (3id). White solid
1
. H NMR (400 MHz, CDCl3) δ
(51.9 mg, 95%). M p 152-153
℃
98%). M p 164-165
℃
. 1H NMR (400 MHz, CDCl3) δ 7.72 – 7.70
7.78 – 7.71 (m, 4H), 7.65 (d, J = 8.0 Hz, 2H), 7.25 (dd, J = 8.2,
3.1 Hz, 4H), 7.01 (s, 1H), 6.78 (d, J = 7.8 Hz, 2H), 6.35 (s, 1H),
5.83 (s, 1H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 165.93,
144.31, 135.73, 135.39, 134.65, 133.95, 133.92, 132.20,
130.77, 129.45, 128.31, 123.93, 123.90, 117.13, 67.11, 21.63.
IR (neat) 3038, 2934, 2861, 1499, 1454, 758, 700, 545 cm-1.
HRMS (ESI) calcd for C24H18BrClN2O4SNa [M+Na]+ 566.9751;
found: 566.9748.
(m, 4H), 7.66 (d, J = 8.1 Hz, 2H), 7.26 - 7.22 (m, 3H), 7.11 (t, J =
7.6 Hz, 2H), 7.04 (s, 1H), 6.89 (brs, 2H), 6.47 (s, 1H), 5.86 (s,
1H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.56, 158.14,
143.76, 137.22, 134.45, 134.02, 130.89, 129.49, 128.09,
127.84, 127.65, 123.37, 116.38, 113.17, 65.91, 54.96, 48.45,
21.50. IR (neat) 3038, 2934, 2861, 1499, 1454, 761, 545 cm-1.
HRMS (ESI) calcd for C24H19ClN2O4SNa [M+Na]+ 489.0646;
found: 489.0644.
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(2-
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-4-methyl-N-(p-
tolyl)benzenesulfonamide (3ed). White solid (43.3 mg, 90%).
fluorophenyl)-4-methylbenzenesulfonamide (3jd). White
solid (44 mg, 91%). M p 178-179
℃
. 1H NMR (400 MHz, CDCl3)
6 | J. Name., 2012, 00, 1-3
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δ 7.73 - 7.65 (m, 8H), 7.26 – 7.20 (m, 4H), 7.14 (s, 1H), 6.38 (s,
1H), 5.84 (s, 1H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
165.86, 160.22 (d, J = 249.6 Hz), 144.11, 136.06, 135.84,
134.46 (d, J = 14.2 Hz), 132.90, 131.86 (d, J = 8.5 Hz), 130.92,
129.30 (d, J = 18.3 Hz), 128.29 (d, J = 26.8 Hz), 125.11, 123.71,
116.66, 115.89 (d, J = 21.4 Hz), 109.95, 66.45, 21.59. IR (neat)
3041, 2934, 2861, 1499, 1454, 758, 545 cm-1. HRMS (ESI)
calcd for C24H22ClFN3O4S [M+NH4]+ 502.0998; found:
502.0992.
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-4-methyl-N-
phenethylbenzenesulfonamide (3od). White solid (48.6 mg,
98%). M p 110-111
℃
. 1H NMR (400 MHz, CDCl3) δ 7.88 – 7.84
(m, 4H), 7.77 – 7.75 (m, 2H), 7.26 (d, J = 7.8 Hz, 2H), 7.14 (t, J
= 7.3 Hz, 2H), 7.01 (t, J = 8.7 Hz, 3H), 6.81 (s, 1H), 5.64 – 5.57
(m, 2H), 3.83 – 3.71 (m, 2H), 2.86 – 2.71 (m, 2H), 2.36 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 166.79, 143.95, 138.24, 136.93,
134.80, 134.58, 131.09, 129.61, 128.73, 128.34, 127.68,
126.19, 123.82, 116.91, 66.50, 48.20, 36.33, 21.48. IR (neat)
3041, 2934, 2861, 1496, 1454, 758, 542 cm-1. HRMS (ESI)
calcd for C26H23ClN2O4SNa [M+Na]+ 517.0959; found:
517.0959.
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(3-
fluorophenyl)-4-methylbenzenesulfonamide (3kd). White
solid (45.0 mg, 93%). M p 175-176
℃.
1H NMR (400 MHz,
CDCl3) δ 7.76 – 7.74 (m, 2H), 7.73 – 7.69 (m, 2H), 7.66 (d, J =
8.2 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H), 7.09 – 7.05 (m, 1H), 7.02
(s, 1H), 6.97 (t, J = 8.3 Hz, 1H), 6.69 (t, J = 8.4 Hz, 2H), 6.36 (s,
1H), 5.84 (s, 1H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
165.94, δ 162.18 (d, J = 248.6 Hz), 144.36, 136.28 (d, J = 9.6
Hz), 135.67, 135.43, 134.62, 130.81, 129.73 (d, J = 9.1 Hz),
129.45, 128.32, 128.20 (d, J = 3.3 Hz), 123.88, 119.84 (d, J =
22.0 Hz), 117.15, 116.72 (d, J = 20.9 Hz), 109.99, 67.19, 21.62.
IR (neat) 3038, 2934, 2861, 1499, 1454, 758, 700, 545 cm-1.
HRMS (ESI) calcd for C24H18ClFN2O4SNa [M+Na]+ 507.0552;
found: 507.0559.
N-butyl-N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-4-
methylbenzenesulfonamide (3pd). White solid (43.7 mg,
1
. H NMR (400 MHz, CDCl3) δ 7.88 – 7.86
98%). M p 88-89
℃
(m, 2H), 7.81 (d, J = 8.1 Hz, 2H), 7.78 – 7.76 (m, 2H), 7.23 (d, J
= 7.9 Hz, 2H), 6.78 (s, 1H), 5.67 (s, 1H), 5.65 (s, 1H), 3.55 (t, J =
8.2 Hz, 2H), 2.35 (s, 3H), 1.53 – 1.44 (m, 1H), 1.36 – 1.25 (m,
1H), 1.15 – 1.06 (m, 2H), 0.74 (t, J = 7.3 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 166.81, 143.67, 137.19, 134.98, 134.64, 131.09,
129.48, 127.60, 123.85, 116.80, 66.50, 46.43, 31.86, 21.47,
20.13, 13.48. IR (neat) 3041, 2934, 2861, 1499, 1454, 758,
702, 542 cm-1. HRMS (ESI) calcd for C22H23ClN2O4SNa [M+Na]+
469.0959; found: 469.0959.
N-(3-bromophenyl)-N-(2-chloro-1-(1,3-dioxoisoindolin-2-
yl)allyl)-4-methylbenzenesulfonamide (3ld). White solid
1
. H NMR (400 MHz, CDCl3) δ
N-benzyl-N-(2-chloro-1-(1,3-dioxoisoindolin-2-
(50.2 mg, 92%). M p 179-180
℃
yl)allyl)methanesulfonamide (3qd). White solid (40.0 mg,
1
. H NMR (400 MHz, CDCl3) δ 7.81 (d, J =
7.78 – 7.70 (m, 4H), 7.65 (d, J = 8.1 Hz, 2H), 7.38 (d, J = 8.0 Hz,
1H), 7.26 (s, 1H), 7.24 (s, 1H), 7.05 – 6.97 (m, 3H), 6.87 (d, J =
8.0 Hz, 1H), 6.35 (s, 1H), 5.84 (s, 1H), 2.41 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 165.94, 144.42, 136.19, 135.56, 135.26,
134.62, 132.57, 131.11, 130.80, 129.98, 129.44, 128.34,
123.90, 121.89, 117.21, 109.99, 67.18, 21.64. IR (neat) 3038,
2934, 2861, 1501, 1454, 758, 702, 545 cm-1. HRMS (ESI) calcd
for C24H18BrClN2O4SNa [M+Na]+ 566.9751; found: 566.9750.
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(3-
99%). M p 92-93
℃
2.4 Hz, 2H), 7.76 (d, J = 2.5 Hz, 2H), 7.11 (d, J = 7.2 Hz, 2H),
7.07 (t, J = 7.3 Hz, 2H), 7.04 – 6.97 (m, 1H), 6.66 (s, 1H), 5.90
(s, 1H), 5.79 (s, 1H), 4.96 (d, J = 16.4 Hz, 1H), 4.81 (d, J = 16.4
Hz, 1H), 2.87 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.96,
135.88, 134.66, 134.59, 130.77, 128.39, 127.42, 127.38,
123.78, 116.55, 66.07, 49.00, 42.09. IR (neat) 3038, 2934,
2861, 1499, 1454, 758, 548 cm-1. HRMS (ESI) calcd for
C19H17ClN2O4SNa [M+Na]+ 427.0490; found: 427.0486.
methoxyphenyl)-4-methylbenzenesulfonamide
White solid (42.5 mg, 86%). M p 155-156
(3md).
1H NMR (400
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-
℃.
phenylacetamide (3rd). White solid (32.1 mg, 91%). M p 121-
122℃
. 1H NMR (400 MHz, CDCl3) δ 7.75 – 7.73 (m, 2H), 7.70 –
MHz, CDCl3) δ 7.73 – 7.67 (m, 6H), 7.26 – 7.23 (m, 2H), 7.01
(brs, 2H), 6.77 (d, J = 7.8 Hz, 1H), 6.44 – 6.38 (m, 3H), 5.86 (s,
1H), 3.44 (s, 3H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
165.90, 159.55, 144.02, 135.91, 135.66, 134.49, 130.91,
129.34, 129.25, 128.45, 124.54, 123.75, 117.54, 116.95,
115.66, 109.98, 67.20, 54.96, 21.60. IR (neat) 3041, 2934,
2861, 1499, 1457, 758, 700, 545 cm-1. HRMS (ESI) calcd for
C25H21ClN2O5SNa [M+Na]+ 519.0752; found: 519.0743.
7.68 (m, 2H), 7.48 – 7.00 (m, 6H), 5.90 (s, 1H), 5.74 (s, 1H),
1.89 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 170.53, 166.23,
138.29, 134.51, 134.35, 130.89, 129.85, 129.37, 129.10,
123.55, 115.30, 64.88, 23.18. IR (neat) 3038, 2934, 2861,
1499, 1454, 758, 542 cm-1. HRMS (ESI) calcd for
C19H15ClN2O3Na [M+Na]+ 377.0663; found: 377.0661.
2-(2-chloro-1-(2-oxooxazolidin-3-yl)allyl)isoindoline-1,3-
1
dione (3sd). Colorless oil liquid (28.2 mg, 92%). H NMR (400
N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)allyl)-N-(3,5-
dimethoxyphenyl)-4-methylbenzenesulfonamide
(3nd).
MHz, CDCl3) δ 7.93 -7.90 (m, 2H), 7.82 – 7.97 (m, 2H), 6.74 (s,
1H), 5.66 (s, 1H), 5.56 (s, 1H), 4.46 – 4.36 (m, 2H), 4.04 – 3.98
(m, 1H), 3.97 – 3.87 (m, 1H). 13C NMR (100 MHz, CDCl3) δ
166.74, 157.46, 134.74, 133.56, 131.22, 123.92, 116.34, 62.77,
62.45, 42.86. IR (neat) 3038, 2934, 2861, 1499, 1454, 758,
700, 545 cm-1. HRMS (ESI) calcd for C14H11ClN2O4Na [M+Na]+
329.0299; found: 329.0299.
White solid (40.5 mg, 77%). M p 209-210
℃.
1H NMR (400
MHz, CDCl3) δ 7.76 – 7.70 (m, 6H), 7.25 (d, J = 8.0 Hz, 2H),
6.98 (s, 1H), 6.40 (s, 1H), 6.30 (s, 1H), 5.99 (brs, 2H), 5.85 (s,
1H), 3.40 (s, 6H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
165.86, 160.23, 144.02, 136.14, 135.86, 135.73, 134.50,
130.94, 129.20, 128.51, 123.71, 116.92, 110.30, 102.05, 67.28,
55.03, 21.56. IR (neat) 3038, 2934, 2861, 1499, 1454, 758,
545 cm-1. HRMS (ESI) calcd for C26H23ClN2O6SNa [M+Na]+
549.0858; found: 549.0859.
(Z)-N-benzyl-N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)-3-
phenylallyl)-4-methylbenzenesulfonamide (3td). White solid
1
. H NMR (400 MHz, CDCl3) δ
(54.6 mg, 98%). M p 195-196
℃
7.63 – 7.59(m, 4H), 7.52 (d, J = 7.8 Hz, 2H), 7.46 (s, 1H), 7.37 –
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7.28 (m, 5H), 7.24 (d, J = 7.6 Hz, 2H), 7.09 (t, J = 7.3 Hz, 2H),
7.05 – 6.99 (m, 1H), 6.94 (d, J = 7.9 Hz, 2H), 6.69 (s, 1H), 5.28
(d, J = 17.4 Hz, 1H), 5.06 (d, J = 17.3 Hz, 1H), 2.17 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 166.23, 143.37, 137.60, 137.01,
135.10, 134.01, 133.34, 131.05, 129.19, 128.63, 128.44,
128.25, 127.87, 127.32, 127.27, 126.82, 123.56, 123.11, 63.40,
51.22, 21.32. IR (neat) 3041, 2931, 2861, 1499, 1457, 758,
700, 545 cm-1. HRMS (ESI) calcd for C31H25ClN2O4SNa [M+Na]+
579.1116; found, 579.1111.
20.86. IR (neat) 3038, 2934, 2861, 1499, 1454, 758, 702, 540
cm-1. HRMS (ESI) calcd for C33H26N2O4SNa [M+Na]+ 569.1505;
found: 569.1503.
Acknowledgements
This work was financially supported by the Fundamental
Research Funds of Central Universities, Southwest University
for Nationalities (2017NZYQN32).
N-benzyl-N-(2-chloro-1-(1,3-dioxoisoindolin-2-yl)-3-
methylbut-2-en-1-yl)-4-methylbenzenesulfonamide (3ud).
White solid (49.9 mg, 98%). M p 164-165
℃
.1H NMR (400
Notes and references
MHz, CDCl3) δ 7.68 – 7.64 (m, 4H), 7.53 (d, J = 7.3 Hz, 4H),
7.30 (t, J = 7.4 Hz, 2H), 7.22 (s, 1H), 7.19 (t, J = 7.2 Hz, 1H),
6.84 (d, J = 8.0 Hz, 2H), 5.18 (d, J = 17.0 Hz, 1H), 5.10 (d, J =
17.0 Hz, 1H), 2.02 (s, 3H), 1.67 (s, 3H), 1.29 (s, 3H). 13C NMR
(100 MHz, CDCl3) δ 166.55, 143.24, 138.83, 138.61, 136.98,
133.95, 131.29, 129.10, 127.79, 127.26, 127.08, 126.98,
123.03, 119.23, 64.28, 51.65, 21.89, 21.15, 20.58. IR (neat)
3041, 2934, 2861, 1499, 1451, 758, 700 cm-1. HRMS (ESI)
calcd for C27H25ClN2O4SNa [M+Na]+ 531.1116; found,
531.1113.
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General Procedure for the Sonogashira cross-coupling
reaction of 3ac with phenylacetylene .
To a suspension of 3ac (0.1 mmol) in anhydrous CH3CN (1.5
mL) were added Et3N (1.5 mL), PdCl2(PPh3)2 (3.5 mg, 5 mol %)
and phenylacetylene (15.3 mg, 1.5 equiv). The reaction vial
was flushed with Ar, and the reaction mixture was stirred for
5 h at 70 °C. Then, the mixture was concentrated under
reduced pressure. The crude material was purified by flash
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N-benzyl-N-(1-(2,5-dioxopyrrolidin-1-yl)-2-methylene-4-
phenylbut-3-yn-1-yl)-4-methylbenzenesulfonamide
(6ac).
White solid (41.3 mg, 83%). M p 125-126
℃.
1H NMR (400
MHz, DMSO) δ 7.65 (d, J = 8.2 Hz, 2H), 7.44 – 7.37 (m, 3H),
7.34 – 7.33 (m, 4H), 7.17 – 7.15 (m, 3H), 7.03 (d, J = 7.4 Hz,
2H), 6.67 (s, 1H), 5.74 (s, 1H), 5.52 (s, 1H), 4.99 (d, J = 17.7 Hz,
1H), 4.72 (d, J = 17.7 Hz, 1H), 2.40 – 2.38 (m, 2H), 2.34 (s, 3H),
2.15 – 2.20 (m, 2H). 13C NMR (100 MHz, DMSO) δ 176.72,
144.39, 137.84, 137.03, 131.84, 130.21, 129.62, 129.19,
128.29, 127.63, 127.20, 126.92, 125.42, 121.91, 91.28, 86.72,
65.89, 49.79, 27.99, 21.48. IR (neat) 3038, 2934, 2861, 1499,
1454, 758, 702, 540 cm-1. HRMS (ESI) calcd for C29H26N2O4SNa
[M+Na]+ 521.1505; found: 521.1507.
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N-benzyl-N-(1-(1,3-dioxoisoindolin-2-yl)-2-methylene-4-
phenylbut-3-yn-1-yl)-4-methylbenzenesulfonamide
(6ae).
White solid (46.0 mg, 84%). M p 57-58
℃
. 1H NMR (400 MHz,
DMSO) δ 7.83 – 7.79 (m, 2H), 7.76 – 7.74 (m, 2H), 7.64 (d, J =
8.2 Hz, 2H), 7.33 (d, J = 7.2 Hz, 1H), 7.28 (t, J = 7.3 Hz, 2H),
7.21 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 6.9 Hz, 2H), 7.03 (d, J = 7.4
Hz, 2H), 6.96 (t, J = 7.3 Hz, 2H), 6.91 (d, J = 7.1 Hz, 1H), 6.87 (s,
1H), 5.79 (s, 1H), 5.60 (s, 1H), 5.08 (d, J = 17.7 Hz, 1H), 4.86 (d,
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166.57, 143.75, 137.20, 136.54, 135.08, 131.03, 130.67,
130.19, 129.60, 129.11, 128.62, 127.57, 127.00, 126.35,
125.21, 123.46, 121.17, 109.54, 91.00, 86.18, 65.42, 49.40,
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DOI: 10.1039/C7OB00882A
Journal Name
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DOI: 10.1039/C7OB00882A
Graphical Abstract
An efficient new method was developed to synthesis of 2-halo allylic aminal derivatives through
regioselective 1,2-addition of allenamides with N-haloimides.
O
R1
CHCl3, r t
R3
.
N
R2
O
O
X
N
X
N
+
R1
R4
N
R2
O
R4
R3
1
2
3
R1 = Aryl, Benzyl, Alkyl; R2 = Ts, Ms, Ac
R3 = H, R4 = Ph; R3 = R4 = Me
X = Cl, Br, I
26 examples, up to 99% yield