Synlett
DOI: 10.1055/s-0036-1590976
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Enaminones by a Palladium-Catalyzed Four-Component Carbonylative Addition Reaction

Liangguang Wang*a, Juan Maa, Xia Chenb, Xiaoyu Zhou*b
  • aCollege of Chemistry and Chemical Engineering, Anshun University, Anshun, 561000, P. R. of China   Email: wang825663@163.com
  • bDepartment of Chemistry and Chemical Engineering, Liupanshui Normal University, Liupanshui, 553004, P. R. of China   Email: zhouxiaoyu20062006@126.com
This work was supported by the Foundation of Science and Technology Department of Guizhou Province (qiankeheJzi [2015] number 2003) and the Doctoral Foundation of Anshun University (asubsjj201501).
Further Information

Publication History

Received: 05 June 2017

Accepted after revision: 03 July 2017

Publication Date:
08 August 2017 (eFirst)

 

Abstract

A palladium-catalyzed carbonylative addition reaction of aryl bromides, amines, and alkynes has been developed. The reaction ­occurs readily in N,N-dimethylformamide with PdCl2(PPh3)2 as a catalyst to give the corresponding enaminones in medium to excellent yields. Furthermore, a mechanism for the palladium-catalyzed four-component carbonylative addition reaction is proposed.


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For economic and environmental reasons, environmentally friendly chemistry has attracted considerable attention in modern organic synthesis.[1] Multicomponent reactions (MCRs)[2] can produce target products directly by simple operations with high efficiency and with reduced waste generation compared with conventional methods in organic synthesis.[3] Palladium-catalyzed carbonylation is a representative MCR[4] that has played an important role in the synthesis of carbonyl compounds because of its high selectivity and mild reaction conditions. In recent years, palladium-catalyzed three-component carbonylative coupling reactions of aryl halides with organometallic reagents, alkenes, alkynes, amines, alcohols, water, or hydrogen have been studied.[5] However, much to our regret, there have been few reports on palladium-catalyzed four-component carbonylations.[6]

Recently, Wu and co-workers reported a palladium-catalyzed four-component carbonylation for the synthesis of 4(3H)-quinazolinones or thiochromenones.[7] In 2014, Bao and co-workers reported the palladium-catalyzed three-component carbonylative addition reaction using 1,4-bis(diphenylphosphino)butane (DPPB) as a ligand in DMF.[8] In the present study, we found that the reductive elimination of the acylpalladium amine intermediate was interrupted by coordination of an alkyne and that a carbonylative addition reaction of an aryl bromide, CO, an amine, and an alkyne successfully occurred with PdCl2(PPh3)2 as catalyst at 120 °C in DMF (Scheme [1]), thereby providing an efficient and novel strategy for the synthesis of enaminones.[9] The method has several prominent advantages over conventional methods, such as mild reaction conditions, high efficiency, simple starting materials, and straightforward operations.

Zoom Image
Scheme 1 Palladium-catalyzed four-component one-pot synthesis of enaminones

Initially, we began our study by using 1-(4-bromophenyl)ethanone (1a, 0.5 mmol), ethynylbenzene (2a, 0.6 mmol), HNEt2 (3a, 0.75 mmol), and CO (5 atm) as substrates and PdCl2 (5 mol%) as a catalyst to optimize the reaction conditions. The expected reaction occurred, and 1-(4-acetylphenyl)-3-(diethylamino)-3-phenylprop-2-en-1-one (4a) was obtained in 20, 22, and 45% yields in the presence of the bidentate ligands DPPB, 1,3-bis(diphenylphosphino)propane (DPPP), and 1,2-bis(diphenylphosphino)ethane (DPPE) respectively (Table [1], entries 1–3). To our delight, however, the isolated yield of product 4a improved to 86% when PPh3 was used as the ligand in DMF solvent (entry 4). A decreased yield of 4a was obtained when the reaction medium DMF was replaced by DMSO, MeCN or 1,4-dioxane (entries 5–7). Note that no product 4a was produced when the reaction was performed in toluene (entry 8). The yield of 4a did not improved significantly when the reaction temperature was increased to 130 °C (entry 9; yield 87%), and the yield of 4a decreased to 65% when the reaction temperature was reduced to 110 °C (entry 10). The optimal reaction temperature is therefore 120 °C. The yield of 4a decreased when K2CO3, K3PO4, Bu3N, or DIPEA was used as an additive (entries 11–14; yield 28–68%). Furthermore, the reaction did not proceed in the absence of an additive (entry 15). Interestingly, the four-component reaction proceed smoothly with PdCl2(PPh3)2 as the catalyst to give product 4a in 86% yield (entry 16).

Table 1 Reaction Condition Screeninga

Entry

Ligand

Solvent

Additive

Yieldb (%)

 1

DPPB

DMF

Et3N

45

 2

DPPP

DMF

Et3N

22

 3

DPPE

DMF

Et3N

20

 4

PPh3

DMF

Et3N

86

 5

PPh3

DMSO

Et3N

58

 6

PPh3

MeCN

Et3N

45

 7

PPh3

1,4-dioxane

Et3N

38

 8

PPh3

toluene

Et3N

NRc

 9d

PPh3

DMF

Et3N

87

10e

PPh3

DMF

Et3N

65

11

PPh3

DMF

K2CO3

28

12

PPh3

DMF

K3PO4

36

13

PPh3

DMF

Bu3N

68

14

PPh3

DMF

DIPEA

62

15

PPh3

DMF

NRc

16f

DMF

Et3N

86

a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), 3a (0.75 mmol), CO (5 atm), PdCl2 (5 mol%), ligand (10 mol%), additive (1.5 mmol), solvent (4 mL), 120 °C, 20 h.

b Isolated yield.

c No reaction; the starting materials were recovered.

d At 130 °C.

e At 110 °C.

f PdCl2(PPh3)2 (5 mol%) was used instead of PdCl2.

From the optimization of the catalytic system, solvent, temperature, and additive, the optimal conditions for the palladium-catalyzed four-component carbonylative addition reaction were identified as follows: PdCl2(PPh3)2 (5 mol%) as catalyst, Et3N (3.0 equiv) as additive, and DMF (4 mL) as solvent in the presence of CO (5atm) at 120 °C for 20 h. Next, we tested the reactivity of various alkynes, aryl bromides, and amines under these optimized reaction conditions.

We first investigated the reactions of various aryl bromides with ethynylbenzene (2a), HNEt2 (3a), and CO under the optimized conditions (Scheme [2]).1-(4-Bromophenyl)ethanone (1a) and 1-(3-bromophenyl)ethanone (1b) gave good yields of products 4a (86%) and 4b (78%), respectively. However, when 1-(2-bromophenyl)ethanone (1c) was used as a substrate, the reaction did not occur. Aryl bromides with an electron-withdrawing group in the para-position 1dh reacted smoothly to give the corresponding products 4dh in moderate to good yields (71–86%). On the other hand, products 4i (58%) and 4j (45%) were produced in lower yields from bromobenzene (1i) and 1-bromonaphthalene (1j), respectively.

Zoom Image
Scheme 2 Palladium-catalyzed carbonylative addition reactions of ­various aryl bromides. Reagents and conditions: 1aj (0.5 mmol), 2a (0.6mmol), 3a (0.75 mmol), CO (5 atm), PdCl2(PPh3) (5mol%), Et3N (1.5 mmol), DMF (4 mL), 120 °C, 20 h. Isolated yields are reported. a The starting materials were recovered.

We then studied the reactivity of various alkynes under the optimal conditions (Scheme [3]). When the aromatic alkynes 2b (R = 4-Tol) and 2c (R = 3-Tol) were subjected in the reaction, the corresponding products 4k and 4l were obtained in excellent yields of 93 and 92%, respectively, whereas 2d (R = 2-Tol) gave only a moderate yield of 4m (78%). Enaminones 4np were produced in excellent yields of 95, 92, and 94%, respectively, from aromatic alkynes containing electron-donating groups in the para-position; however, lower yields were obtained when the aromatic alkynes contained electron-withdrawing groups in the para-position (4q; 56%: 4r; 53%). Interestingly, for aromatic alkyne 2j with a vinyl group in the para-position, product 4s (85%) was obtained, showing that the palladium-­catalyzed carbonylative addition is highly selective towards the C≡C triple bond. More importantly, aliphatic alkynes ethynylcyclohexane (2k) and oct-1-yne (2l) and the heterocyclic alkyne 3-ethynylpyridine (2m) also reacted under the optimal conditions to give products 4t (84%), 4u (82%), and 4v (91%), respectively, in high yields.

Zoom Image
Scheme 3 Palladium-catalyzed carbonylative addition reaction of various terminal alkynes. Reagents and conditions: 2a (0.5 mmol), 2bm (0.6mmol), 3a (0.75 mmol), CO (5 atm), PdCl2(PPh3)2 (5mol%), Et3N (1.5 mmol), DMF (4 mL), 120 °C, 20 h. Isolated yields are reported.

Next, we used several secondary and primary amines in the palladium-catalyzed carbonylative addition reaction (Scheme [4]). The secondary amines dimethylamine (3b) and dibutylamine (3c) gave products 4w (87%) and 4x (91%), respectively, in high yields. Primary amine butylamine (3d) gave a lower yield of product 4y (46%). However, the reaction did not occur smoothly when aniline (3e) was used.

Zoom Image
Scheme 4 Palladium-catalyzed carbonylative addition reactions of various amines

To explore the mechanism of this reaction, we performed several control experiments (Scheme [5]). The reaction of bromide 1a, ethynylbenzene (2a), and CO did not occur in DMF at 120 °C for 20 h (Scheme [1], eq 1), whereas the reaction of bromide 1a, diethylamine (3a), and CO did occur under these conditions to give the corresponding product 5a in 92% yield (Scheme [1], eq 2). These results show that, in the four-component carbonylative reaction system, the reaction occurs initially between the aryl bromide, the amine, and CO, rather than the aryl bromide, the alkyne, and CO.

Zoom Image
Scheme 5 Control experiments

Finally, a plausible reaction mechanism (Scheme [6]) is proposed based on the control experiments and the reported mechanism of palladium-catalyzed carbonylation.[10] Bromide 1a undergoes oxidative addition with Pd(0) to form the arylpalladium intermediate A. Subsequently, this undergoes CO insertion to produce an acylpalladium intermediate B, which react with nucleophile 3a to produce intermediate C in the presence of Et3N. The reductive elimination of intermediate C is interrupted by the coordination of 2a to give the π-alkyne(acyl)palladium intermediate D.[11] Insertion then occurs to form intermediate E, which gives a Pd(0) species and product 4a through reductive elimination.

Zoom Image
Scheme 6 Proposed reaction mechanism

In summary, we have developed a new type of palladium-catalyzed one-pot carbonylative addition reaction of aryl bromides, alkynes, and amines. The reductive elimination of an acylpalladium amine intermediate is interrupted by the coordination of an alkyne, and a carbonylative addition reaction occurs smoothly to produce enaminones in moderate to excellent yields.[12] Fortunately, the present method has distinct advantages, such as compatibility with many functional groups, high selectivity, simplicity of the catalytic system and substrates, and mild reaction conditions. The principle of the reaction will provide a new strategy for developing new types of catalytic carbonylative addition reactions of alkenes.


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Supporting Information

  • References and Notes

  • 1 van der Heijden G. Ruijter E. Orru RV. A. Synlett 2013; 24: 666
    • 2a Rotstein BH. Zaretsky S. Rai V. Yudin AK. Chem. Rev. 2014; 114: 8323
    • 2b Estévez V. Villacampa M. Menéndez JC. Chem. Soc. Rev. 2014; 43: 4633
    • 2c Slobbe P. Ruijter E. Orru RV. A. Med. Chem. Commun. 2012; 3: 1189
    • 2d Touré BB. Hall DG. Chem. Rev. 2009; 109: 4439

      For selected reviews, see:
    • 3a Cioc RC. Ruijter E. Orru RV. A. Green Chem. 2014; 16: 2958
    • 3b Guo X. Hu W. Acc. Chem. Res. 2013; 46: 2427
    • 3c Gu Y. Green Chem. 2012; 14: 2091
    • 3d Estévez V. Villacampa M. Menéndez JC. Chem. Soc. Rev. 2010; 39: 4402
    • 3e D’Souza DM. Müller TJ. J. Chem. Soc. Rev. 2007; 36: 1095
    • 3f Dömling A. Chem. Rev. 2006; 106: 17
    • 4a Shen C. Wu X.-F. Chem. Eur. J. 2017; 23: 2973
    • 4b Peng J.-B. Qi X. Wu X.-F. Synlett 2017; 28: 175

      For selected reviews, see:
    • 5a Dong K. Wu X.-F. Angew. Chem. Int. Ed. 2017; 56: 5399
    • 5b Wu X.-F. RSC Adv. 2016; 6: 83831
    • 5c Wu X.-F. Neumann H. Beller M. Chem. Rev. 2013; 113: 1
    • 5d Wu X.-F. Neumann H. Beller M. Chem. Soc. Rev. 2011; 40: 4986
    • 5e Liu Q. Zhang H. Lei A. Angew. Chem. Int. Ed. 2011; 50: 10788
    • 5f Brennführer A. Neumann H. Beller M. Angew. Chem. Int. Ed. 2009; 48: 4114
    • 5g Barnard CF. J. Organometallics 2008; 27: 5402
    • 5h Modern Carbonylation Methods . Kollár L. Wiley-VCH; Weinheim; 2008

      For selected papers, see:
    • 6a Shen C. Spannenberg A. Auer M. Wu X.-F. Adv. Synth. Catal. 2017; 359: 941
    • 6b Torres GM. Quesnel JS. Bijou D. Arndtsen BA. J. Am. Chem. Soc. 2016; 138: 7315
    • 6c Zhao J. Li Z. Song S. Wang M.-A. Fu B. Zhang Z. Angew. Chem. Int. Ed. 2016; 55: 5545
    • 6d Wang Q. He Y.-T. Zhao J.-H. Qiu Y.-F. Zheng L. Hu J.-Y. Yang Y.-C. Liu X.-Y. Liang Y.-M. Org. Lett. 2016; 18: 2664
    • 6e Liu J. Han Z. Wang X. Wang Z. Ding K. J. Am. Chem. Soc. 2015; 137: 15346
    • 6f Cheng J. Qi X. Li M. Chen P. Liu G. J. Am. Chem. Soc. 2015; 137: 2480
    • 6g Sumino S. Ui T. Ryu I. Org. Lett. 2013; 15: 3142
    • 6h Fusano A. Sumino S. Fukuyama T. Ryu I. Org. Lett. 2011; 13: 2114
    • 7a Shen C. Spannenberg A. Wu X.-F. Angew. Chem. Int. Ed. 2016; 55: 5067
    • 7b He L. Li H. Neumann H. Beller M. Wu X.-F. Angew. Chem. Int. Ed. 2014; 53: 1420
  • 8 Zhang S. Wang L. Feng X. Bao M. Org. Biomol. Chem. 2014; 12: 7233

    • For selected papers and reviews, see:
    • 9a Zhu Z. Tang X. Li J. Li X. Wu W. Deng G. Jiang H. Chem. Commun. 2017; 53: 3228
    • 9b Yang Z. Jiang B. Hao W.-J. Zhou P. Tu S.-J. Li G. Chem. Commun. 2015; 51: 1267
    • 9c Shi L. Xue L. Lang R. Xia C. Li F. ChemCatChem 2014; 6: 2560
    • 9d Yu X. Wang L. Feng X. Bao M. Yamamoto Y. Chem. Commun. 2013; 49: 2885
    • 9e Cheng G. Zeng X. Shen J. Wang X. Cui X. Angew. Chem. Int. Ed. 2013; 52: 13265
    • 9f Zhao Y. Deng D.-S. Ma L.-F. Ji B.-M. Wang L.-Y. Chem. Commun. 2013; 49: 10299
    • 9g Wu X.-F. Sundararaju B. Neumann H. Dixneuf PH. Beller M. Chem. Eur. J. 2011; 17: 106
    • 9h Cacchi S. Fabrizi G. Filisti E. Org. Lett. 2008; 10: 2629
    • 9i Elassar A.-ZA. El-Khair AA. Tetrahedron 2003; 59: 8463
  • 10 Wu X.-F. Neumann H. Beller M. Chem. Eur. J. 2010; 16: 9750
  • 11 Cacchi S. Fabrizi G. Chem. Rev. 2005; 105: 2873
  • 12 Enaminones 4a–z; General Procedure A mixture of the appropriate aryl bromide 1 (0.5 mmol), alkyne 2 (0.6 mmol), amine 3 (0.75 mmol), PdCl2(PPh3)2 (17.5 mg, 5 mol%), Et3N (209 μL, 1.5 mmol), and DMF (4.0 mL) was placed in a 25 mL autoclave under N2. The autoclave was filled with CO to 5 atm pressure, and heated to 120 °C for 20 h. The product was extracted with EtOAc (3 × 5 mL), and the organic layers were combined, washed with brine (2 × 5 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was then purified by chromatography (silica gel). 1-(4-Acetylphenyl)-3-(diethylamino)-3-phenylprop-2-en-1-one (4a) Pale-yellow solid; yield: 138.2 mg (86%,); mp 96−98 °C. IR (neat): 3474, 3059, 2976, 1683, 1625, 1479, 1461, 1439, 1357, 1265, 1213, 775 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.0 Hz, 2 H), 7.87 (d, J = 8.0 Hz, 2 H), 7.45–7.23 (m, 5 H), 5.93 (s, 1 H), 3.51–2.90 (m, 4 H), 2.59 (s, 3 H), 1.47–0.94 (m, 6 H). 13C NMR (100 MHz, CDCl3): δ = 198.0, 185.9, 164.1, 146.2, 138.2, 137.0, 128.7, 128.5, 128.1, 127.8, 127.7, 93.1, 44.8, 26.9, 14.4. HRMS (EI): m/z [M+] calcd for C21H23NO2: 321.1729; found: 321.1735.

  • References and Notes

  • 1 van der Heijden G. Ruijter E. Orru RV. A. Synlett 2013; 24: 666
    • 2a Rotstein BH. Zaretsky S. Rai V. Yudin AK. Chem. Rev. 2014; 114: 8323
    • 2b Estévez V. Villacampa M. Menéndez JC. Chem. Soc. Rev. 2014; 43: 4633
    • 2c Slobbe P. Ruijter E. Orru RV. A. Med. Chem. Commun. 2012; 3: 1189
    • 2d Touré BB. Hall DG. Chem. Rev. 2009; 109: 4439

      For selected reviews, see:
    • 3a Cioc RC. Ruijter E. Orru RV. A. Green Chem. 2014; 16: 2958
    • 3b Guo X. Hu W. Acc. Chem. Res. 2013; 46: 2427
    • 3c Gu Y. Green Chem. 2012; 14: 2091
    • 3d Estévez V. Villacampa M. Menéndez JC. Chem. Soc. Rev. 2010; 39: 4402
    • 3e D’Souza DM. Müller TJ. J. Chem. Soc. Rev. 2007; 36: 1095
    • 3f Dömling A. Chem. Rev. 2006; 106: 17
    • 4a Shen C. Wu X.-F. Chem. Eur. J. 2017; 23: 2973
    • 4b Peng J.-B. Qi X. Wu X.-F. Synlett 2017; 28: 175

      For selected reviews, see:
    • 5a Dong K. Wu X.-F. Angew. Chem. Int. Ed. 2017; 56: 5399
    • 5b Wu X.-F. RSC Adv. 2016; 6: 83831
    • 5c Wu X.-F. Neumann H. Beller M. Chem. Rev. 2013; 113: 1
    • 5d Wu X.-F. Neumann H. Beller M. Chem. Soc. Rev. 2011; 40: 4986
    • 5e Liu Q. Zhang H. Lei A. Angew. Chem. Int. Ed. 2011; 50: 10788
    • 5f Brennführer A. Neumann H. Beller M. Angew. Chem. Int. Ed. 2009; 48: 4114
    • 5g Barnard CF. J. Organometallics 2008; 27: 5402
    • 5h Modern Carbonylation Methods . Kollár L. Wiley-VCH; Weinheim; 2008

      For selected papers, see:
    • 6a Shen C. Spannenberg A. Auer M. Wu X.-F. Adv. Synth. Catal. 2017; 359: 941
    • 6b Torres GM. Quesnel JS. Bijou D. Arndtsen BA. J. Am. Chem. Soc. 2016; 138: 7315
    • 6c Zhao J. Li Z. Song S. Wang M.-A. Fu B. Zhang Z. Angew. Chem. Int. Ed. 2016; 55: 5545
    • 6d Wang Q. He Y.-T. Zhao J.-H. Qiu Y.-F. Zheng L. Hu J.-Y. Yang Y.-C. Liu X.-Y. Liang Y.-M. Org. Lett. 2016; 18: 2664
    • 6e Liu J. Han Z. Wang X. Wang Z. Ding K. J. Am. Chem. Soc. 2015; 137: 15346
    • 6f Cheng J. Qi X. Li M. Chen P. Liu G. J. Am. Chem. Soc. 2015; 137: 2480
    • 6g Sumino S. Ui T. Ryu I. Org. Lett. 2013; 15: 3142
    • 6h Fusano A. Sumino S. Fukuyama T. Ryu I. Org. Lett. 2011; 13: 2114
    • 7a Shen C. Spannenberg A. Wu X.-F. Angew. Chem. Int. Ed. 2016; 55: 5067
    • 7b He L. Li H. Neumann H. Beller M. Wu X.-F. Angew. Chem. Int. Ed. 2014; 53: 1420
  • 8 Zhang S. Wang L. Feng X. Bao M. Org. Biomol. Chem. 2014; 12: 7233

    • For selected papers and reviews, see:
    • 9a Zhu Z. Tang X. Li J. Li X. Wu W. Deng G. Jiang H. Chem. Commun. 2017; 53: 3228
    • 9b Yang Z. Jiang B. Hao W.-J. Zhou P. Tu S.-J. Li G. Chem. Commun. 2015; 51: 1267
    • 9c Shi L. Xue L. Lang R. Xia C. Li F. ChemCatChem 2014; 6: 2560
    • 9d Yu X. Wang L. Feng X. Bao M. Yamamoto Y. Chem. Commun. 2013; 49: 2885
    • 9e Cheng G. Zeng X. Shen J. Wang X. Cui X. Angew. Chem. Int. Ed. 2013; 52: 13265
    • 9f Zhao Y. Deng D.-S. Ma L.-F. Ji B.-M. Wang L.-Y. Chem. Commun. 2013; 49: 10299
    • 9g Wu X.-F. Sundararaju B. Neumann H. Dixneuf PH. Beller M. Chem. Eur. J. 2011; 17: 106
    • 9h Cacchi S. Fabrizi G. Filisti E. Org. Lett. 2008; 10: 2629
    • 9i Elassar A.-ZA. El-Khair AA. Tetrahedron 2003; 59: 8463
  • 10 Wu X.-F. Neumann H. Beller M. Chem. Eur. J. 2010; 16: 9750
  • 11 Cacchi S. Fabrizi G. Chem. Rev. 2005; 105: 2873
  • 12 Enaminones 4a–z; General Procedure A mixture of the appropriate aryl bromide 1 (0.5 mmol), alkyne 2 (0.6 mmol), amine 3 (0.75 mmol), PdCl2(PPh3)2 (17.5 mg, 5 mol%), Et3N (209 μL, 1.5 mmol), and DMF (4.0 mL) was placed in a 25 mL autoclave under N2. The autoclave was filled with CO to 5 atm pressure, and heated to 120 °C for 20 h. The product was extracted with EtOAc (3 × 5 mL), and the organic layers were combined, washed with brine (2 × 5 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was then purified by chromatography (silica gel). 1-(4-Acetylphenyl)-3-(diethylamino)-3-phenylprop-2-en-1-one (4a) Pale-yellow solid; yield: 138.2 mg (86%,); mp 96−98 °C. IR (neat): 3474, 3059, 2976, 1683, 1625, 1479, 1461, 1439, 1357, 1265, 1213, 775 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.0 Hz, 2 H), 7.87 (d, J = 8.0 Hz, 2 H), 7.45–7.23 (m, 5 H), 5.93 (s, 1 H), 3.51–2.90 (m, 4 H), 2.59 (s, 3 H), 1.47–0.94 (m, 6 H). 13C NMR (100 MHz, CDCl3): δ = 198.0, 185.9, 164.1, 146.2, 138.2, 137.0, 128.7, 128.5, 128.1, 127.8, 127.7, 93.1, 44.8, 26.9, 14.4. HRMS (EI): m/z [M+] calcd for C21H23NO2: 321.1729; found: 321.1735.

Zoom Image
Scheme 1 Palladium-catalyzed four-component one-pot synthesis of enaminones
Zoom Image
Scheme 2 Palladium-catalyzed carbonylative addition reactions of ­various aryl bromides. Reagents and conditions: 1aj (0.5 mmol), 2a (0.6mmol), 3a (0.75 mmol), CO (5 atm), PdCl2(PPh3) (5mol%), Et3N (1.5 mmol), DMF (4 mL), 120 °C, 20 h. Isolated yields are reported. a The starting materials were recovered.
Zoom Image
Scheme 3 Palladium-catalyzed carbonylative addition reaction of various terminal alkynes. Reagents and conditions: 2a (0.5 mmol), 2bm (0.6mmol), 3a (0.75 mmol), CO (5 atm), PdCl2(PPh3)2 (5mol%), Et3N (1.5 mmol), DMF (4 mL), 120 °C, 20 h. Isolated yields are reported.
Zoom Image
Scheme 4 Palladium-catalyzed carbonylative addition reactions of various amines
Zoom Image
Scheme 5 Control experiments
Zoom Image
Scheme 6 Proposed reaction mechanism