Palladium(II)-catalyzed regioselective carbonylative coupling of aniline derivatives with terminal aryl acetylenes to give acrylamides under syngas conditions

Article abstract of DOI:10.1016/S0040-4039(00)00899-6

The carbonylative coupling of aniline derivatives (1a-h) with terminal aryl acetylenes (2a, b) catalyzed by Pd(OAc)₂ and 1,4- bis(diphenylphosphino)butane (dppb) under syngas conditions affords acrylamide derivatives 3 or 3' in excellent yields

Full text of DOI:10.1016/S0040-4039(00)00899-6

Tetrahedron Letters 41 (2000) 5761±5764
Palladium(II)-catalyzed regioselective carbonylative coupling
of aniline derivatives with terminal aryl acetylenes to give
acrylamides under syngas conditions
B. El Ali,* A. El-Ghanam, M. Fettouhi and J. Tijani
Chemistry Department, KFUPM, 31261 Dhahran, Saudi Arabia
Received 5 April 2000; accepted 2 June 2000
Abstract
The carbonylative coupling of aniline derivatives (1a±h) with terminal aryl acetylenes (2a, b) catalyzed
by Pd(OAc)2 and 1,4-bis(diphenylphosphino)butane (dppb) under syngas conditions a€ords acrylamide
derivatives 3 or 30 in excellent yields and selectivities. # 2000 Published by Elsevier Science Ltd.
Keywords: palladium; carbonylative coupling; aniline; alkynes; acrylamides; syngas.
Amides represent an important class of organic compounds for both industrial applications
and academic research.1 The use of transition metal complexes in carbonylation chemistry is an
ecient route for the production of carbonyl compounds.2,3 The classical synthesis of some N-aryl
acrylamides is known to be achieved by reacting aromatic amines with methacrylyl chlor-
ides.4,12,13 2-Substituted acrylamides are important intermediates for polymer synthesis5 and have
been synthesized by palladium-catalyzed carbonylation of terminal alkynes with diethylamine in
a strongly acidic medium6 or in the presence of organic iodides or amine HI salts.7 Recently, the
selective synthesis of a,b-unsaturated amides has been achieved via palladium(0)-catalyzed insertion
of carbon monoxide into an unactivated carbon nitrogen bond of propargylamines and 2,3-
dienylamines.8,9 We now wish to report a direct and highly ecient palladium-catalyzed method
of a regioselective carbonylative coupling of aniline derivatives with terminal aryl acetylenes,
a€ording acrylamides under syngas conditions.
The palladium-catalyzed reaction of aniline (la, R1ˆPh, R2ˆH) with phenylacetylene (2a,
R3ˆPh) and syngas mixture was chosen as a model reaction to determine the optimum reaction
conditions (see Eq. (1)).
* Corresponding author.
0040-4039/00/$ - see front matter # 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)00899-6

5762
ꢀ1†
The carbonylation of aniline with phenylacetylene was examined by varying the ratio of CO/
H2, in the presence of 1 mol% of Pd(OAc)2 and 2 mol% of 1,4-bis(diphenylphosphino)butane
(dppb) at 600 psi and 110ꢁC in toluene as a solvent. Low total yields (31%) of N-2-diphenyl
propeneamide (3a, R1ˆPh, R2ˆH, R3ˆPh) and trans-N,3-diphenyl propeneamide (4a, R1ˆPh,
R2ˆH, R3ˆPh) (ratio of 3a/4a=92/8) were obtained when only carbon monoxide was applied.
However, the use of the syngas mixture in the reaction signi®cantly increases the yields of the
unsaturated amides, depending on the CO/H2 ratio. Total yields of 60%, 90%, and 85% of 3a
and 4a were obtained with the ratios of CO/H2 of 5/1, 1/1, and 1/5, respectively. Furthermore, the
decrease in the total pressure to 200 psi (CO/H2=1/1) and the reaction time to 24 h decreases the
total yield of products to 59% and 60%, respectively. The e€ect of varying the palladium catalyst
and phosphine ligand on the total yield of 3a and 4a was also realized at 110ꢁC and in the pre-
sence 600 psi of syngas mixture (CO/H2=1/1). Pd(OAc)2 gave only traces of 3a and 4a in the
absence of any phosphine ligand, however, the use of system Pd(OAc)2/PPh3 gives a total yield of
75% of products. Furthermore, the use of the bidentate phosphine ligand 1,2-bis(diphenylpho-
sphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), or dppb, gives acrylamide 3a
with total yields of 85%, 82%, and 90%, respectively. In addition, the nature of the solvent
greatly a€ects the yield of acrylamides, for example, the use of dichloromethane in place of tolu-
ene with the catalytic system Pd(OAc)2/dppb/CO/H2 gave only 40% of products. The use of
other palladium complexes, such as PdCl2, PdCl2(PPh3)2, Pd(dba)2, and Pd(PPh3)4 with dppb
gave low yields (10±20%) of acrylamides.
The scope of this new methodology for the catalytic synthesis of acrylamides was demonstrated
by the results summarized in Table 1. The carbonylative coupling reaction of a series of aniline
derivatives (1a±h) with terminal aryl acetylenes (2a,b) was performed using 1 mol% of Pd(OAc)2
and 2 mol% of dppb at 600 psi of a mixture of syngas (CO/H2=1/1). The unsaturated amides
3a±h (30a±h) and 4a±h (40a±h) were isolated in total yields ranging between 67% and 95%. Aniline
and N-substituted aniline derivatives (1a±g) reacted with phenylacetylene (2a) or with p-tolylace-
tylene (2b) (Table 1, entries 1±7) a€ording the acrylamides 3 or 30 as the major products. The
reaction exhibits high regioselectivity in favor of the acrylamides 3 or 30. The regiochemical out-
come is in excellent accord with the related palladium-catalyzed hydrocarboxylation of
alkynes.10,11 However, the aminophenol derivative (1h) reacts with 2a or 2b (Table 1, entry 8)
forming 3h or 30h as the sole products.
Interestingly, the carbonylative coupling of acetanilide 1i with phenylacetylene 2a at 130ꢁC,
catalyzed by the system Pd(OAc)2/dppb/CO/H2 in toluene, a€ords an acceptable total yield and
excellent regioselectivity of the unsaturated amide 5 (Eq. (2)).
ꢀ2†

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Table 1
Palladium(II)-catalyzed carbonylative coupling of aniline derivatives with terminal aryl acetylenesa
The role of H2 is probably to stabilize the palladium hydride intermediate `dppb-Pd-H' formed
during the catalytic cycle.
The typical experimental procedure was as follows. To a 45 ml Parr autoclave ®tted with a
glass liner and stirring bar was added Pd(OAc)2 (0.02 mmol), dppb (0.04 mmol), phenylacetylene
(2.0 mmol), aniline (2.0 mmol), and toluene (10 ml). The autoclave system was vented three times
with CO and then pressurized with 300 psi of CO and 300 psi of H2. The mixture was stirred at
110ꢁC for 48 h. After cooling, the pressure was released, the reaction mixture was ®ltered and the
solvent was removed. The products 3a and 4a were separated by recrystallization and preparative
thin-layer chromatography (petroleum ether:acetone=10:1). The products identi®ed by NMR,
FT-IR, and GC-MS gave satisfactory spectral data.
The following compounds are known: 4a,12 4d.13 All other unsaturated amides 3 and 4 are new
compounds. Representative examples of spectral data of two unsaturated amides are provided:

5764
1
N,2-Diphenyl propeneamide (3a): IR (neat) ꢀ (cm^1) 1652 (CO), 3230 (NH); H NMR ꢁ (ppm):
5.72 (s, 1H, ˆCH2), 6.29 (s, 1H, ˆCH2), 7.10±7.52 (m, 11H, 2Ph and NH); 13C NMR ꢁ (ppm):
119.93, 123.36, 124.63, 128.87, 129.02, 136.67, 137.65, 145.11, 165.20; GC±MS m/z 223 (M+).
Anal. calcd for C15H13NO: C, 80.69; H, 5.87; N, 6.27. Found: C, 80.75; H, 6.08; N, 6.34. trans-N-
Phenyl-3-tolyl propeneamide (40a): IR (neat) ꢀ (cm^1) 1656 (CO), 3286 (NH); H NMR ꢁ (ppm):
1
2.36 (s, 3H, CH3), 6.53 (d, 1H, J=15.5 Hz, COCHˆ), 7.10±7.62 (m, 10H, arom. and NH), 7.72
(d, 1H, J=15.5 Hz, ˆCH-tolyl); 13C NMR ꢁ (ppm): 21.45, 119.98, 124.40, 127.96, 129.06, 129.61,
131.87, 138.10, 140.32, 142.41, 164.48; GC±MS m/z 237 (M+). Anal. calcd for C16H15NO: C,
80.98; H, 6.37; N, 5.90. Found: C, 79.95; H, 6.37; N, 5.85.
In conclusion, the palladium-catalyzed carbonylative coupling of anilines with aryl alkynes and
syngas provides a remarkably ecient method for the synthesis of new acrylamides in high isolated
yields and regioselectivities. This methodology demonstrates again the eciency of palladium
catalysts in useful carbonylative coupling reactions. We are currently examining the application
of this catalytic system to di€erent classes of substances including primary and secondary alkyl
amines and diamines with terminal and internal alkyl and aromatic alkynes, diynes, and others.
Acknowledgements
We thank the King Fahd University of Petroleum and Minerals (KFUPM-Saudi Arabia) for
®nancial support of this project.
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