Palladium-catalyzed aminocarbonylation of alkynes to succinimides

Article abstract of DOI:10.1021/jo502412v

Succinimide derivatives are useful building blocks for the synthesis of natural products and drugs. We describe an efficient route to succinimide derivatives comprising Pd(xantphos)Cl₂-catalyzed aminocarbonylation of alkynes with aromatic or aliphatic amines in the presence of p-TsOH. The utility of this route is demonstrated with the synthesis of a large number of succinimide compounds including an important photochromic molecule.

Full text of DOI:10.1021/jo502412v

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Article
Palladium-catalyzed Aminocarbonylation of Alkynes to Succinimides
Huizhen Liu, Genevieve P.S Lau, and Paul Joseph Dyson
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 23 Nov 2014
Downloaded from http://pubs.acs.org on November 24, 2014
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The Journal of Organic Chemistry
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Palladium-catalyzed Aminocarbonylation of Alkynes to Suc-
cinimides
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Huizhen Liu*, Genevieve P. S. Lau, and Paul J. Dyson*
Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Swit-
zerland.
huizhen.liu@epfl.ch, paul.dyson@epfl.ch
ABSTRACT: Succinimide derivatives are useful building blocks for the synthesis of natural products and drugs. We describe an
efficient route to succinimide derivatives comprising Pd(xantphos)Cl2–catalyzed aminocarbonylation of alkynes with aromatic or
aliphatic amines in the presence of p-TsOH. The utility of this route is demonstrated with the synthesis of a large number of succin-
imide compounds including an important photochromic molecule.
INTRODUCTION
Cyclic imides are important compounds that have numerous applications in chemistry, biology and material science. Succin-
imide derivatives, a sub-class of cyclic imides, are of particular interest due to the prevalence of the succinimide moiety in nature.
Consequently, succinimides are useful building blocks for the synthesis of natural products as well as pharmaceutical and agro-
chemical compounds, including palasimide1, salfredins2, phensuximide3, and 2-quindinephthalimide (Figure 1).
Figure 1. Examples of bioactive compounds containing cyclic imide (succinimide) moieties.
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Succinimide derivatives may be prepared using a variety of methods. Classical approaches include condensation reactions be-
tween anhydrides and amines at high temperatures or in the presence of Lewis acids3,4 and the cyclization of amic acids3,5. More
recent approaches include iridium-catalyzed multicomponent synthesis of glutarimides6, ring expansion of 4-formyl-β-lactams7,
iron-catalyzed carbonylative succinimide synthesis using an alkyne, CO and amine8, ruthenium- or palladium-catalyzed carbonyla-
tion of aromatic compounds affording phthalimides9, rhodium-catalyzed 1,4-addition of aryl boronic acids to maleimides giving
chiral 3-substituted succinimide derivatives10 and the direct synthesis of cyclic imides from simple diols using a ruthenium-based
catalyst11.While some succinimide derivatives may be obtained through the aforementioned routes, others are more challenging to
synthesize and would benefit from a more efficient and sustainable process12.
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Figure 2. The effect of reaction parameters on the yield of N-phenyl-succinimide (1 mmol aniline, 1.2 mmol phenyacetylene, 0.05 mmol
Pd(xantphos)Cl2). (a) Influence of CO pressure at 125°C for 4 h in the presence of 0.8 mmol p-TsOH. (b) The effect of the p-TsOH concentra-
tion at 125°C, under 30 atm. CO for 4 h. (c) The effect of reaction temperature under 30 atm. CO for 4 h in the presence of 0.8 mmol p-TsOH.
(d) Influence of reaction time at 125°C, under 30 atm. CO with 0.01 mmol Pd(xantphos)Cl2 in the presence of 0.8 mmol p-TsOH.
Carbonylation reactions are widely employed in organic synthesis to generate amides, esters and carboxylic acids13. In earlier
studies, an efficient system was developed for the aminocarbonylation of alkenes to yield branched or linear amides14. As an exten-
sion of this work, we investigated the applicability of the palladium-based catalyst for the aminocarbonylation of alkynes. Ami-
nocarbonylation of alkynes generally yields branched or linear α, β-unsaturated amides, as documented in the literature15. With our
system, however, we found that the major products were succinimide derivatives. Herein, we describe this route to succinimides
and demonstrate the scope of the reaction that allows access to both N-alkyl- and N-phenyl-succinimide derivatives. As mentioned
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above, the iron-catalyzed carbonylative succinimide synthesis using an alkyne, CO and amine has been reported8, however in con-
trast to our system the iron-catalyzed is only active for aliphatic amines.
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Table 1. Optimization of the reaction of phenylacetylene with aniline and CO to afford N-phenyl succinimide.
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Entry
1
Pre-catalyst
PdCl2/xantphos
Pd(xantphos)Cl2
Pd(dppf)Cl2
Solvent
THF
Yield (%)
97
2
THF
97
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THF
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Pd(PPh3)2Cl2
THF
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Pd(dppe)Cl2
THF
trace
trace
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Pd(dppb)Cl2
THF
7
Pd(OAc)2/xantphos
Pd(acac)2/xantphos
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Pd(xantphos)Cl2
Pd2(dba)3/xantphos
Pd(PPh3)4
THF
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THF
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9
CH3CN
toluene
hexane
H2O
84
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68
54
10
DMF
THF
trace
95
THF
trace
Reaction conditions: phenylacetylene (1.2 mmol), aniline (1 mmol), pre-catalyst (5 mol% based on aniline), xantphos (0.12 mmol), p-TsOH (0.8 mmol),
THF (10 ml), CO (30 atm), 125oC, 4 h. dppe = 1,2-bis(diphenylphosphino)ethane, dppf = 1,10-bis(diphenylphosphino)ferrocene, dppb = 1,2-
bis(diphenylphosphino)benzene, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. Yields were determined by GC analysis relative to aniline
using n-decane as an internal standard.
RESULTS AND DICUSSION
The reaction of phenylacetylene and aniline in the presence of CO and p-TsOH and catalytic amounts of Pd(xantphos)Cl2, that
contains a wide bite-angle bis-phosphine, was initially studied16. The effects of CO pressure, reaction time, reaction temperature
and the amount of acid co-catalyst were examined (Figure 2). The yield of the desired N-phenyl-succinimide product is greatest
under 30 atmospheres of CO – at higher pressures the yield decreases and the intermolecular product, 2-benzyl-N1, N3-
diphenylmalonamide, is obtained. The amount of acid co-catalyst also has a large influence on the yield of N-phenyl-succinimide.
In the absence of the acid co-catalyst the yield of N-phenyl-succinimide is < 6%, whereas at 0.8 mmol of p-TsOH the desired prod-
uct is obtained in 97% yield and at higher concentrations of acid the yield decreases. High temperatures and long reaction times are
required in order to obtain N-phenyl-succinimide in high yield. After just 2 hours the main product is the α, β-unsaturated amide,
which is consumed as the reaction continues, with the concomitant growth in yield of N-phenyl-succinimide, implying a two-step
reaction sequence. First, aminocarbonylation of phenylacetylene with aniline yields a branched (or linear) α, β-unsaturated amide.
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Second, an intermolecular reaction with CO generates the N-phenyl-succinimide product. However, it is possible that other reaction
pathways may also be operating (see below).
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Table 2. Substrate scope of the Pd(xantphos)Cl2-catalyzed aminocarbonylation of alkynes (1a) with amines (2a).
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3a2b2
Yield: 92%
3a3b3
Yield: 98%
3a1b1
Yield: 96%
3a5b5
Yield: trace
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Yield: trace
3a4b4
Yield: 93%
3a8b8
Yield: 93%
3a9b9
Yield: 94%
3a7b7
Yield: 93%
3a11b11
Yield 87%
3a12b12
Yield: 93%
3a10b10
Yield: 90%
3a14b14
Yield: 92%, trans/cis: 98/2
3a13b13
Yield: 92%
3a15b15
Yield: 90%
3a16b16
Yield: 13%
3a17b17
Yield: 20%
3a18b18
Yield: 20%
Reaction conditions: Pd(xantphos)Cl2 (5 mol% based on aniline), 1a (1mmol), 2b (1.2 mmol), CO (30 atm), 125oC, 8 h, p-TsOH (0.8 mmol), Yields are
isolated yields. For 3a16b16, 3a17b17, and 3a18b18, yields were determined by GC analysis relative to aniline with n–decane as an internal standard.
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Under the optimized conditions the activity of Pd(xantphos)Cl2 is the same as a mixture PdCl2 and xantphos which presumably
forms the complex in situ (Table 1, entries 1 and 2). Other metal complexes were also evaluated (Table 1, entries 2-5), however,
none were as effective as Pd(xantphos)Cl2. Other palladium salts were also evaluated in combination with the xantphos ligand
instead of PdCl2, i.e. Pd(OAc)2 or Pd(acac)2, but the yield of N-phenyl-succinimide was lower with these salts (Table 1, entries 7
and 8). Interestingly, the Pd(0) precursor, Pd2(dba)3, in combination with xantphos exhibits good activity, with the yield of the
desired product reaching 95% (Table 1, entry 14). In contrast, Pd(PPh3)4 is inactive with only trace amounts of the product detected
(Table 1, entry 15). The nature of the solvent is also important, with THF resulting in highest yields, and lower yields obtained in
DMF, CH3CN, hexane, toluene and water (Table 1, entries 1 and 9-13).
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The scope of the reaction was explored under optimized conditions using Pd(xantphos)Cl2 (5 mol%) as the catalyst (Table 2).
The system is most efficient for anilines with electron-donating substituents. In contrast, anilines with electron-withdrawing sub-
stituents afford only trace amounts of succinimide product, i.e. 3a5b5 and 3a6b6 in Table 2, although in the latter case, steric reasons
are also likely to be responsible for the low yield. Interestingly, reaction with 3-aminobenzonitrile does not give a succinimide,
instead the product 3a4b4 is obtained in 93% yield. Substituents on phenylacetylene do not appear to have a large effect on the
reaction, and both electron-donating and electron-withdrawing substituents give succinimide products in good yield, e.g. 3a7b7,
3a8b8 and 3a9b9 in Table 2. The system catalyzes both terminal and internal alkynes in high yield, e.g. 3a13b13, 3a14b14, 3a15b15, and
aromatic and aliphatic alkynes in yields around 90%. Both aromatic and aliphatic amines may be employed although the aromatic
amines give much higher yields (85 – 90% vs. < 20%) of the succinimide products. In this respect, it should be noted that the ma-
jority of routes to succinimide derivatives have focused on N-alkyl-succinimides and the synthesis of N-phenyl-succinimides is
more challenging. Moreover, N-phenyl-succinimides, and the structurally related N-phenylmaleimides (which may be obtained
from N-phenyl-succinimides via dehydrogenation17), have a number of important applications18,19 . N-phenyl-succinimides may be
converted to their non-aromatic analogues via a simple exchange reaction at room temperature.20 The reverse reaction, however, is
not facile.
To demonstrate the utility of the Pd(xantphos)Cl2-catalyzed method an important photochromic molecule21 was pre-
pared using this procedure (Scheme 1). Notably, the corresponding alkyne can be prepared in a facile manner using the
palladium-catalyzed Sonogashira reaction. The alkyne then reacts with CO to form the N-phenyl-succinimide product.
From the alkyne to the final product only three steps are required and compared with the literature method the starting
materials used in our route are easily prepared and are much cheaper.
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Scheme 1. The synthesis of the photochromic molecule 7.
The full mechanistic details of this reaction have not been determined, but presumably involve aminocarbonylation of
the alkyne as the first step with the resulting alkene transferred into the second step where the succinimide is formed. A
possible reaction mechanism is shown in Scheme 2, the first cycle involves the formation of an α, β-unsaturated amide by
intermolecular reaction; the reaction mechanism should be similar to the hydroformylation of alkynes to α, β-unsaturated
aldehydes reported previously22. The carbon-carbon double bond of α, β-unsaturated amide can be further activated by the
catalyst14, reacting with CO to form the final product (the second cycle in Scheme 2).
Scheme 2. Proposed mechanism.
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In conclusion, we have shown that Pd(xantphos)Cl2 efficiently catalyzes the carbonylation of alkynes with CO and
amines to yield succinimide derivatives in the presence of p-TsOH. The reaction may be applied to both aliphatic and
aromatic amines and represents an ideal method to transform simple starting materials into valuable succinimide deriva-
tives.
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Experimental section:
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Catalytic procedure
A mixture of the desired amount of pre-catalyst, ligand, alkyne, amine, p-TsOH and THF (10 ml) was added to a teflon
tube that was placed in an autoclave (autoclave volume = 30 ml). The autoclave was sealed and purged with carbon mon-
oxide to remove the air and then charged with the required pressure of CO. The reaction mixture was stirred at a required
temperature for required time. After cooling the CO was released and the reaction mixture was purified by flash column
chromatography on silica gel to afford the desired product. The yield of the product was determined by weighing the iso-
lated product or by GC analysis.
Procedure for the preparation of 3,4-diaryl-2,5-dihydropyrroles
2,5-dimethyl-3-bromofuran (1) or 2,5-dimethyl-3-bromothiophene (2)
N-bromosuccinimide (NBS) (10 mmol) was slowly added to 50 mL of a glacial acetic acid solution containing 2,5-
dimethylthiophene (for 1, 10 mmol) or 2,5-dimethylfuran (for 2, 10 mmol) at room temperature. After stirring for 3 h the solution
was poured onto excess ice-cold water and the product extracted with dichloromethane. The dichloromethane solution was washed
with an aqueous sodium carbonate solution (20 ml) and water (30 ml). The organic layer was washed with water (2 x 15 ml), dried
over MgSO4 and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatog-
raphy on silica gel using hexane as the eluent. Yield of 1 is82% and 2 is 67%.
3-ethynyl-2,5-dimethylthiophene (3)
A 25 mL Schlenk tube was charged with Pd(PPh3)4 (0.5 mol %), PPh3 (1 mol %), and copper iodide (1 mol %). TMEDA (1 M), 2
(3 mmol) and ethynyltrimethylsilane (1.2 equiv.) were added successively under a nitrogen atmosphere. The solution was stirred for
20 h at 80oC and then cooled to room temperature and K2CO3 (3 mmol) was added and the mixture stirred for a further 3 h. The
residue was purified by column chromatography on silica gel using hexane as the eluent to afford the product in 42% yield.
3-((2,5-dimethylthiophen-3-yl)ethynyl)-2,5-dimethylfuran (4)
A 25 mL Schlenk tube was charged with Pd(PPh3)4 (0.5 mol %), PPh3 (1 mol %), copper iodide (1 mol %). TMEDA (1 M), 1 (3
mmol), and 3 (1.2 equiv.) were added successively under a nitrogen atmosphere. The reaction mixture was heated at 80oC for 20 h.
After cooling to room temperature, the mixture was quenched with water (15 mL) and the aqueous phase was extracted with diethyl
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ether (3 x 20 mL). The organic phases were combined, dried over anhydrous Na2SO4 and concentrated under vacuum and the resi-
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due was purified by silica gel column chromatography using hexane as the eluent. The product yield of 4 is 72%.
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3-(2,5-dimethylfuran-3-yl)-4-(2,5-dimethylthiophen-3-yl)-1-(4-methoxyphenyl)pyrrolidine-2,5-dione
dimethylfuran-3-yl)-4- (2,5-dimethylthiophen-3-yl)-1-(4-methoxyphenyl)-1H-pyrrole-2,5-dione (6)
(5)
and
3-(2,5-
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A mixture of PdCl2 (0.05 mmol), xantphos (0.06 mmol), 3-((2,5-dimethylthiophen-3-yl)ethynyl)-2,5-dimethylfuran (1 mmol), 4-
methoxyaniline (1 mmol), p-TsOH (0.8 mmol) and THF (10 ml) was added to a teflon tube that was placed in an autoclave (volume
= 30 ml). The autoclave was sealed and purged with carbon monoxide to remove the air and then charged with CO (30 atm). The
reaction mixture was stirred at 125oC for 12 h. After cooling the CO was released and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ 1.2 equiv.) was added and the resulting mixture was stirred for 3 h at room temperature. The product was purified by flash
column chromatography on silica gel using ethyl acetate and hexane as the eluent to afford the product in 76% yield.
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3-(2,5-dimethylfuran-3-yl)-4-(2,5-dimethylthiophen-3-yl)-1-(4-methoxyphenyl)-2,5-dihydro-1H-pyrrole (7)
Compound 6 (1 mmol) was dissolved in dry THF (10 ml) and added dropwise to a suspension of LiAlH4 in THF. The reaction
mixture was stirred for 5 h at 0oC, and then water (1 ml) and 15% NaOH solution (1 ml) was added and the mixture stirred for 1 h
at 0oC. Water (3 ml) was added to the reaction mixture and the product was extracted into CH2Cl2. The solvent was removed under
vacuum and the product was purified by flash column chromatography on silica gel using ethyl acetate and hexane as the eluent to
afford the product in 46% yield.
Spectroscopic data
1,3-diphenylpyrrolidine-2,5-dione(3ab) White solid (243 mg, 97% yield): mp 136−138°C; 1H NMR (400 MHz, CDCl3) δ
7.51 (td, J = 6.9, 1.6 Hz, 2H), 7.48 – 7.40 (m, 3H), 7.41 – 7.29 (m, 5H), 4.23 (dd, J = 9.8, 4.8 Hz, 1H), 3.42 (dd, J = 18.6,
9.7 Hz, 1H), 3.04 (dd, J = 18.5, 4.8 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 176.6, 175.1, 137.2, 132.0, 129.3, 129.2,
128.7, 128.1, 127.4, 126.5, 46.0, 37.3. HRMS (ESI): calculated for C16H13NO2 [M+Na]+ 274.0844, found 274.0843.
1
1-(2,6-dimethoxyphenyl)-3-phenylpyrrolidine-2,5-dione (3a1b1) White solid (298 mg, 96% yield): mp 200−203°C; H
NMR (400 MHz, CDCl3) δ 7.54 – 7.38 (m, 2H), 7.36 (dt, J = 8.6, 6.4 Hz, 3H), 6.53 (t, J = 2.2 Hz, 1H), 6.48 (d, J = 2.2 Hz,
2H), 4.21 (dd, J = 9.7, 4.8 Hz, 1H), 3.40 (dd, J = 18.5, 9.7 Hz, 1H), 3.03 (dd, J = 18.5, 4.9 Hz, 1H). 13C NMR (101 MHz,
CDCl3) δ 176.5, 175.0, 161.1, 137.1, 133.4, 129.3, 128.1, 127.4, 105.0, 101.2, 55.6, 45.6, 37.2. HRMS (ESI): calculated
for C18H17NO4 [M+Na]+ 334.1055, found 334.1050.
1-(3-fluorophenyl)-3-phenylpyrrolidine-2,5-dione (3a2b2) White solid (247 mg, 92% yield): mp 146−148°C; 1H NMR
(400 MHz, CDCl3) δ 7.55 – 7.30 (m, 6H), 7.21 – 7.10 (m, 3H), 4.23 (dd, J = 9.7, 4.8 Hz, 1H), 3.42 (dd, J = 18.6, 9.7 Hz,
1H), 3.05 (dd, J = 18.6, 4.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 176.2, 174.7, 163.8, 161.4, 136.8, 133.2, 133.1, 130.4,
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130.3, 129.4, 128.2, 127.4, 122.1, 122.1, 115.9, 115.7, 114.2, 113.9, 45.9, 37.2. HRMS (ESI): calculated for C16H12FNO2
[M+Na]+ 292.0750, found 292.0748.
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3-phenyl-1-(o-tolyl)pyrrolidine-2,5-dione (3a3b3) White solid (259 mg, 98% yield): mp 162−163°C; 1H NMR (400 MHz,
CDCl3) δ 7.45 (t, J = 7.0 Hz, 2H), 7.42 – 7.25 (m, 6H), 7.14 (dd, J = 13.8, 7.8 Hz, 1H), 4.27 (td, J = 9.9, 4.7 Hz, 1H), 3.45
(ddd, J = 18.6, 9.7, 3.9 Hz, 1H), 3.07 (ddd, J = 18.5, 10.6, 4.7 Hz, 1H), 2.21 (d, J = 17.4 Hz, 3H). 13C NMR (101 MHz,
CDCl3) δ 176.7, 175.3, 139.1, 137.1, 131.9, 129.2, 128.9, 128.7, 128.1, 126.5, 124.3, 46.0, 37.4, 21.5. HRMS (ESI): cal-
culated for C17H15NO2 [M+Na]+ 288.1000, found 288.0997.
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N1,N4-bis(3-cyanophenyl)-2-phenylsuccinamide (3a4b4) White solid (367 mg, 93% yield); H NMR (400 MHz, DMSO-
d6) δ 10.60 (s, 1H), 10.42 (s, 1H), 8.15 – 8.01 (m, 2H), 7.76 (ddt, J = 13.3, 7.5, 2.4 Hz, 2H), 7.57 – 7.20 (m, 9H), 4.27 (dd,
J = 9.8, 5.2 Hz, 1H), 3.26 (dd, J = 16.1, 9.7 Hz, 1H), 2.82 (dd, J = 16.1, 5.3 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ
172.1, 170.4, 155.7, 140.4, 140.2, 139.6, 130.7, 129.1, 128.0, 127.7, 127.2, 127.1, 124.0, 123.9, 122.0, 121.9, 119.1, 119.1,
112.0, 68.2, 48.3. HRMS (ESI): calculated for C24H18N4O2 [M+Na]+ 417.1328, found 417.1320.
1-phenyl-3-(3-(trifluoromethyl)phenyl)pyrrolidine-2,5-dione (3a7b7) White solid (249 mg, 93% yield): mp 170−173 °C;
1H NMR (400 MHz, CDCl3) δ 7.68 – 7.49 (m, 6H), 7.48 – 7.42 (m, 1H), 7.40 – 7.32 (m, 2H), 4.31 (dd, J = 9.8, 5.2 Hz,
1H), 3.46 (dd, J = 18.5, 9.8 Hz, 1H), 3.05 (dd, J = 18.5, 5.2 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 175.9, 174.4, 137.8,
131.7, 130.8, 129.9, 129.3, 128.9, 126.4, 125.1, 124.5, 105.0, 45.5, 36.9. HRMS (ESI): calculated for C17H12F3NO2
[M+Na]+ 342.0718, found 342.0702.
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3-(4-methoxyphenyl)-1-phenylpyrrolidine-2,5-dione (3a8b8) White solid (297 mg, 93% yield): mp 170−173°C; H NMR
(400 MHz, CDCl3) δ 7.55 – 7.47 (m, 2H), 7.46 – 7.40 (m, 1H), 7.38 – 7.33 (m, 2H), 7.29 – 7.24 (m, 2H), 6.99 – 6.93 (m,
2H), 4.18 (dd, J = 9.7, 4.8 Hz, 1H), 3.85 (s, 3H), 3.40 (dd, J = 18.5, 9.7 Hz, 1H), 3.01 (dd, J = 18.6, 4.8 Hz, 1H). 13C NMR
(101 MHz, CDCl3) δ 176.7, 175.2, 159.3, 132.0, 129.2, 129.0, 128.7, 128.4, 126.5, 114.7, 55.4, 45.3, 31.1. HRMS (ESI):
calculated for C17H15NO3 [M+Na]+ 304.0950, found 304.0951.
1-phenyl-3-(m-tolyl)pyrrolidine-2,5-dione (3a9b9) White solid (249 mg, 94% yield): mp 180−181°C; 1H NMR (400 MHz,
CDCl3) δ 7.57 – 7.40 (m, 3H), 7.30 (m, 3H), 7.19 (m, 3H), 4.19 (dd, J = 9.7, 4.7 Hz, 1H), 3.40 (dd, J = 18.6, 9.7 Hz, 1H),
3.03 (dd, J = 18.6, 4.7 Hz, 1H), 2.41 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 176.73, 175.3, 139.1, 137.1, 132.0, 129.2,
128.9, 128.7, 128.1, 126.5, 124.3, 46.0, 37.4, 21.5. HRMS (ESI): calculated for C17H15NO2 [M+Na]+ 288.1000, found
288.1003.
3-benzyl-1-phenylpyrrolidine-2,5-dione (3a10b10) White solid (238 mg, 90% yield): mp 148−150°C; 1H NMR (400 MHz,
CDCl3) δ 7.53 – 7.30 (m, 6H), 7.28 – 7.17 (m, 4H), 3.43 – 3.22 (m, 2H), 3.12 (dd, J = 13.8, 8.0 Hz, 1H), 2.92 (dd, J = 18.5,
9.1 Hz, 1H), 2.68 (dd, J = 18.5, 4.7 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 178.2, 175.2, 136.7, 131.8, 129.2, 129.2,
128.9, 128.6, 127.3, 126.5, 41.3, 36.6, 33.4. HRMS (ESI): calculated for C17H15NO2 [M+Na]+ 288.1000, found 288.1003.
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N-phenyl-2-(trimethylsilyl)acrylamide (3a11b11) White solid (191 mg, 87% yield); 1H NMR (400 MHz, CDCl3) δ 7.62 (d,
J = 7.7 Hz, 2H), 7.43 – 7.32 (m, 3H), 7.26 (d, J = 18.5 Hz, 1H), 7.15 (d, J = 14.8 Hz, 1H), 6.37 (d, J = 18.5 Hz, 1H), 0.19
(s, 9H). 13C NMR (101 MHz, CDCl3) δ 163.1, 145.8, 137.9, 136.9, 129.0, 124.4, 119.9, -1.73; HRMS (ESI): calculated
for C12H17NOSi [M+Na]+ 242.0977, found 242.0977.
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3-butyl-1-phenylpyrrolidine-2,5-dione (3a12b12) White solid (215 mg, 93% yield): mp 70−71 °C; H NMR (400 MHz,
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CDCl3) δ 7.54 – 7.45 (m, 2H), 7.46 – 7.37 (m, 1H), 7.37 – 7.26 (m, 2H), 3.30 – 2.79 (m, 2H), 2.64 – 2.55 (m, 1H), 2.12 –
1.95 (m, 1H), 1.52 – 1.32 (m, 5H), 1.01 – 0.93 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 179.0, 175.7, 132.0, 129.1, 128.5,
126.5, 40.0, 34.6, 31.2, 28.8, 22.4, 13.9. HRMS (ESI): calculated for C14H17NO2 [M+Na]+ 254.1157, found 254.1157.
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3,4-diethyl-1-phenylpyrrolidine-2,5-dione (3a13b13) White solid (213 mg, 92% yield): mp 65−66°C; H NMR (400 MHz,
CDCl3) δ 7.69 – 7.55 (m, 2H), 7.46 (s, 1H), 7.42 – 7.32 (m, 2H), 7.19 – 7.08 (m, 1H), 6.26 (t, J = 7.3 Hz, 1H), 2.44 (q, J =
7.5 Hz, 2H), 2.25 (p, J = 7.5 Hz, 2H), 1.11 (td, J = 7.6, 2.1 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 167.7, 138.8, 138.2,
136.5, 129.0, 124.1, 119.9, 21.4, 20.5, 13.8. HRMS (ESI): calculated for C14H17NO2 [M+Na]+ 254.1157, found 254.1157.
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3-butyl-4-methyl-1-phenylpyrrolidine-2,5-dione (3a14b14) White solid (225 mg, 92% yield): mp 75−76°C; H NMR (400
MHz, CDCl3) δ 7.52 – 7.46 (m, 2H), 7.40 (ddd, J = 6.6, 4.8, 1.9 Hz, 1H), 7.31 (dd, J = 8.4, 1.2 Hz, 2H), 2.70 (qd, J = 7.3,
5.3 Hz, 1H), 2.57 (dt, J = 8.7, 5.0 Hz, 1H), 2.10 – 1.94 (m, 1H), 1.80 – 1.63 (m, 1H), 1.48 (d, J = 7.3 Hz, 4H), 1.42 (ddd, J
= 11.0, 7.0, 3.9 Hz, 3H), 0.97 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 178.9, 178.1, 132.1, 129.1, 128.4, 126.4,
48.1, 41.1, 30.6, 28.9, 22.6, 16.6, 13.9. HRMS (ESI): calculated for C15H19NO2 [M+Na]+ 268.1308 found 268.1313.
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1,3,4-triphenylpyrrolidine-2,5-dione (3a15b15) White solid (294 mg, 90% yield): mp 243−244°C; H NMR (400 MHz,
CDCl3) δ 7.53 (m, 2H), 7.49 – 7.34 (m, 10H), 7.34 – 7.29 (m, 3H), 4.26 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 175.6,
136.6, 132.0, 129.4, 129.2, 128.8, 128.2, 127.7, 126.5, 55.5. HRMS (ESI): calculated for C22H17NO2 [M+Na]+ 350.1157,
found 350.1154.
ASSOCIATED CONTENT
Supporting Information
NMR spectra of all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the EPFL and the Swiss National Science Foundation. We also thank for Dr Peng Gao (Laboratory of Photon-
ics and Interfaces, EPFL) for helpful discussions.
REFERENCES
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