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Synlett 2023; 34(06): 667-672
DOI: 10.1055/a-1934-1189
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Chemical Synthesis and Catalysis in India

Use of Polymer-Supported 4-(N,N-Dimethylamino)pyridine in a Formal Conjugate Addition/Elimination Mediated by an N-Ylide Generated In Situ for the Construction of Highly Functionalized Itaconimides/Alkenes

Suman K. Saha‡
,
Anshul Jain‡
,
Akanksha Kumari
,
Tshering Sangmo Bhutia
,
Chanchal Agrawat
,
Nirmal K. Rana  ∗

This work was financially supported by the Science and Engineering Research Board (SERB), India, (CRG/2020/001940) and the Council of Scientific and Industrial Research (CSIR), India, (02(0424)/21/EMR-II).
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Abstract

A simple, mild, and metal-free cascade reaction has been developed for the construction of highly functionalized olefins. The approach relies on the initial formation of [3+2]-cycloadducts from a pyridinium ylide generated in situ from polymer-bound DMAP (PS-DMAP) with an N-substituted maleimide or an α,β-unsaturated β-keto ester. The cycloadduct decomposes to regenerate supported DMAP and yield a functionalized itaconimide or olefin. The method has a broad substrate scope. The alkene product has been further transformed into trisubstituted furan. PS-DMAP could be reused for five cycles.


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Key words

dimethylaminopyridine - heterogeneous catalysis - ylides - cycloaddition - itaconimides - alkenes

Table 1 Optimization of the Reaction of N-Benzylmaleimide Mediated by an N-Ylide Prepared In Situa

Entry

Base

Solvent

Temp (°C)

Time (h)

Yield (%)

 1

Et3N (0.2)

toluene

rt

72

16

 2

Et3N (0.5)

toluene

rt

72

22

 3

Et3N (0.5)

toluene

50

48

24

 4

Et3N (0.5)

toluene

80

48

45

 5

Et3N (1.0)

toluene

80

 8

77

 6

Et3N (1.0)

EtOAc

80

48

19

 7

Et3N (1.0)

DCE

80

12

58

 8

Et3N (1.0)

m-xylene

80

28

60

 9

Et3N (1.0)

MeCN

80

 8

65

10

K2CO3 (1.0)

toluene

80

48

24

11

Cs2CO3 (1.0)

toluene

80

48

30

12

DBU (1.0)

toluene

80

 6

15

13

DBN (1.0)

toluene

80

 6

16

14

DIPEA (1.0)

toluene

80

12

68

a Reaction conditions: 2-bromoacetophenone (1a; 119.4 mg, 0.6 mmol), N-benzylmaleimide (3a; 74.8 mg, 0.4 mmol), PS-DMAP (240 mg), solvent (1 mL), AcOH (0.16 mmol).

Ammonium ylide-mediated C–C and C–X bond-formation reactions have recently attracted considerable attention in organic synthesis.[1] Despite the challenges in stability and selectivity associated with N-ylides, many efficient approaches leading to nitrogen-containing heterocycles through 1,3-dipolar addition reactions have been documented.[2] Another characteristic reaction of ammonium ylides is the formal [n+1] cyclization, which relies on the nucleophilic addition of the ylide to an activated alkene, followed by an intramolecular substitution.[3] The latter approach has made great progress through the exploitation of N-ylides as C1 synthons with a diverse range of reaction partners having an electrophilic and suitably placed nucleophilic reaction centers. There are a few recent reports on asymmetric versions of this reaction that make use of chiral amines, usually commercially available cinchona alkaloids.[4] Although the chemistry of ammonium ylides has made significant advances in recent decades, the exploration of alternative reaction pathways for the development of efficient and concise methodologies for syntheses of highly functionalized molecules, especially under metal-free and mild conditions, remains of great interest to the synthetic community. In particular, the potential of pyridinium ylides to promote the cascade conjugate addition–elimination (CA-E) reaction in synthesizing functionalized alkenes remains underexplored. Nevertheless, Tsuge and co-workers demonstrated an efficient silica-gel-mediated elimination of pyridine from the cycloadducts formed by the reaction of pyridinium methylides with N-substituted maleimides or activated olefins.[5] However, the substrate scope was mainly limited to preformed unsubstituted phenacyl pyridinium salts and N-tolyl-substituted maleimides. Chiral pyrrolidinyl sulfonamides (1.5 to 2.0 equivalents) have also been found to be suitable for promoting tandem CA-E reactions of activated allylic bromides with dialkyl dithiomalonates.[6]

Solid-supported catalysts and reagents have found widespread application in the synthesis of interesting organic molecules in both academia and industry.[7] Supported pyridine derivatives, especially PyBOX derivatives, have been used as ligands to form metal complexes that have been employed in a variety of catalytic reactions.[8] On the other hand, 4-dimethylaminopyridine (DMAP) has been immobilized on various solid supports, such as silica, alumina, or polystyrene, and the catalytic activities of these novel supported DMAP products have been investigated.[9] We reasoned that polymer-linked pyridines might be used as immobilized reagents/catalysts in valuable synthetic methods by exploiting the potential of the ylide chemistry of nitrogen. Immobilized pyridines can easily be separated from reaction mixtures, simplifying purification procedures, and they can often be recycled for reuse. Here we report that a pyridinium ylide generated in situ from polymer-supported DMAP can be used to mediate the construction of highly functionalized itaconimides or trisubstituted alkenes.

We began our investigation with the reaction of N-benzylmaleimide (3a) with the phenacyl pyridinium bromide 2a, generated in situ by the reaction of 2-bromoacetophenone (1a) with polystyrene-supported DMAP (PS-DMAP);[10] the reaction was performed in the presence of a catalytic amount of base (Table [1], entry 1). After continuing the reaction at rt for 72 hours, only 16% of product 4aa was detected. However, increasing the amount of base and the reaction temperature led to significant improvements in the yield of 4aa (entries 2–5).

Zoom Image
Scheme 1 Substrate scope of the PS-DMAP-mediated reactions of in-situ-generated N-ylides with N-substituted maleimides. Reagents and conditions: 1 (0.6 mmol), 3 (0.4 mmol), PS-DMAP (240 mg), toluene (1 mL), Et3N (0.4 mmol), AcOH (0.16 mmol). The reported reaction times are those taken to consume the maleimide 3, as monitored by TLC.

We noticed that a minimum of 1.0 equivalents of base were required to obtain a synthetically viable yield (entry 5). During our optimization of the reaction conditions, we observed that after the N-benzylmaleimide had been consumed, the addition of a catalytic amount of acetic acid was essential for the effective elimination of the DMAP polymer through decomposition of the initially formed cycloadduct; a similar observation was previously reported by Tsuge et al.[5] Toluene as a solvent and triethylamine as a base were found the most suitable among several solvents and bases screened for the reaction (Table [1], entries 5–14). Importantly, we observed that the E-alkene product was formed selectively in all cases.

Having optimized the reaction conditions,[11] we attempted to generalize the formal conjugate addition/elimination reaction with respect to various α-bromo ketones 1 with N-benzylmaleimide (3a) to test the substrate tolerance (Scheme [1]). α-Bromoacetophenones bearing chloro (1b) or methoxy (1c) groups in the para-position reacted smoothly to provide the expected itaconimides 4ba and 4ca, respectively, in good yields. 1-Biphenyl-4-yl-2-bromoethanone (1d) and 2-bromo-1-(2-naphthyl)ethanone (1e) gave the corresponding products 4da and 4ea in synthetically viable yields. Importantly, 2-bromo-1-(2-thienyl)ethanone (1f) was also well tolerated in the reaction affording product 4fa in 51% yield. Next, various α-bromo aliphatic ketones, for example, 1g, were subjected to the optimized reaction conditions. To our delight, the corresponding pyridinium salt with PS-DMAP was formed and subsequently reacted with N-benzylmaleimide (3a) or N-methylmaleimide (3b) to afford the corresponding products 4ga and 4gb in moderate to good yields. Next, N-methylmaleimide was allowed to react with several in-situ-formed pyridinium ylides, and moderate to good yields were obtained in all the cases. N-Phenylmaleimide was also successfully employed in the reaction. It is worth mentioning that all the N-substituted itaconimides were isolated exclusively as the E-isomers.

Table 2 Substrate Scope of the PS-DMAP-Mediated Reactions of In Situ Generated N-Ylides with N-Substituted Maleimidesa

Entry

R1

R3

Timeb (h)

Product

Yieldc (%)

 1

1a

Ph

5a

Ph

 8

6aa

78

 2

1a

Ph

5b

4-ClC6H4

 8

6ab

70 (1:0.9)

 3

1a

Ph

5c

4-BrC6H4

10

6ac

72 (1:0.9)

 4

1a

Ph

5d

4-MeOC6H4

12

6ad

75 (1:0.7)

 5

1a

Ph

5e

4-O2NC6H4

14

6ae

69 (1:0.6)

 6

1a

Ph

5f

2-naphthyl

12

6af

75 (1:0.9)

 7

1a

Ph

5g

2-(benzo[1,3]dioxol-5-yl)

14

6ag

70 (1:0.8)

 8

1a

Ph

5h

3,4-Cl2C6H3

16

6ah

78(1:0.7)

 9

1a

Ph

5i

2-thienyl

16

6ai

68 (1:0.7)

10

1a

Ph

5j

Me

18

6aj

67 (1:0.7)

11

1h

4-BrC6H4

5a

Ph

10

6ha

66 (1:0.9)

12

1i

4-MeC6H4

5a

Ph

14

6ia

74 (1:0.9)

13

1j

4-O2NC6H4

5a

Ph

14

6ja

65 (1:0.6)

a Reaction conditions: 1 (0.6 mmol), 5 (0.4 mmol), PS-DMAP (240 mg), toluene (1 mL), Et3N (0.4 mmol), AcOH (0.16 mmol).

b Time for consumption of keto ester 5 as monitored by TLC.

c Combined yield of an inseparable mixture of isomeric products.

To further expand the scope of the formal CA-E reaction mediated by the polymer-supported N-ylide, we employed α,β-unsaturated β-keto ester 5a under the same optimized reaction conditions (Table [2], entry 1). We were pleased to observe the formation of the trisubstituted olefin 6aa in 78% yield as the E-isomer.[12] The geometry of the trisubstituted alkene 6aa was elucidated by NOSEY spectroscopy.[13] Next, the substituent at the para-position of the aryl ring of the α,β-unsaturated β-keto ester was varied and 5b–e (chloro, bromo, methoxy, and nitro derivatives) were employed in the reactions; although the reaction proceeded efficiently, inseparable mixtures of isomeric products 6ab–ae were isolated in all cases (entries 2–5). Keto esters containing a naphthyl or benzo[1,3]dioxolyl group were also investigated (entries 6 and 7). The reactions proceeded smoothly with a disubstituted aryl (5h), hetaryl (5i), or alkyl (5j) keto ester (entries 8–10). Various 2-bromoacetophenones (1h, 1i, and 1j) were also tested with 5a, and the corresponding trisubstituted alkenes 6ha, 6ia, and 6ja were isolated in good to excellent yields (entries 11–13).

To gain insight into the formation of the intermediate cycloadduct, two separate experiments were conducted with simple DMAP and N-benzylmaleimide (3a) or the α,β-unsaturated β-keto ester 5a. The mass spectra of the crude reaction mixtures (Figure [1]) showed the presence of cyclic adducts, confirming the initial formation of [3+2]-cycloadducts from the electrophiles and the reactive ylides generated in situ.

Zoom Image
Figure 1 Detection of intermediate cycloadduct by HRMS of the crude reaction mixture

To demonstrate the synthetic potential of the present method, gram-scale reactions were carried out. The formal conjugate addition-elimination reactions on a gram scale of both the electrophile [e.g., N-benzylmaleimide (3a)] and the α,β-unsaturated β-keto ester (e.g., 5a) gave the corresponding products 4aa and 6aa without loss of efficiency (Scheme [2]; upper). PS-DMAP was recovered almost quantitatively. The recovered polymer was tested under the optimized reaction conditions for five successive cycles of reaction. Notably, a slight decrease in the isolated yield was observed after each cycle (Scheme [2]; lower).

Zoom Image
Scheme 2 Gram-scale reactions and recycling of PS-DMAP

Moreover, the formal addition/elimination reactions could be conducted by using homogeneous DMAP as a mediator. DMAP (1.8 equiv) was treated with 2-bromoacetophenone (1a; 1.5 equiv) in toluene at 80 °C to form a pyridinium salt. Further one-pot cascade reactions with maleimides or activated alkenes in the presence of a base furnished the corresponding products in slightly lower yields than those of the comparable PS-DMAP-mediated reactions (Scheme [3]).

Zoom Image
Scheme 3 DMAP-mediated formal addition/elimination reactions

Next, the functionalized alkene product 6aa was subjected to iodine-catalyzed cyclization conditions, and trisubstituted furan 7aa was formed in 65% yield (Scheme [4]).[14]

Zoom Image
Scheme 4 Synthetic modification of a functionalized olefin to a trisubstituted furan

In summary, we have successfully employed polymer-bound DMAP with various α-bromo ketones to obtain N-ylides in situ, and have applied these in the facile construction of N-substituted itaconimides exclusively as the E-isomers or highly functionalized olefins as inseparable mixtures of isomeric products in synthetically viable yields. Gram-scale reactions were equally efficient. A product was transformed into a trisubstituted furan in a single step.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

Provision of the HRMS facility from DST, India, under a FIST Grant and the research infrastructure facilities of IIT Jodhpur are gratefully acknowledged. We thank Dr. Khyati Shukla (IIT Kanpur) for fruitful help. S.K.S., A.J., and A.K. thank the Ministry of Education, India for research fellowships.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1934-1189.
  • Supporting Information

  • References and Notes

  • 6 Xu J, Fu X, Low R, Goh Y.-P, Jiang Z, Tan C.-H. Chem. Commun. 2008; 5526-5528
    CrossrefPubMed
  • 10 During our initial optimization of the reaction conditions, we found that a minimum of 1.8 equivalents (based on DMAP content) of PS-DMAP (~3.0 mmol/g DMAP loading; matrix crosslinked with 2% divinylbenzene) is essential for effective formation of the pyridinium salt.
  • 11 (3E)-1-Benzyl-3-(2-oxo-2-phenylethylidene)pyrrolidine-2,5-dione (4aa); Typical Procedure A mixture of α-bromoacetophenone (1a; 119.4 mg, 0.6 mmol) and PS-DMAP (240 mg, 0.72 mmol) in toluene (1 mL) was stirred at 80 °C for 8 h. After complete consumption of 1a, N-benzylmaleimide (3a;74.8 mg, 0.4 mmol) and Et3N (55.8 μL, 0.4 mmol) were added, and the mixture was stirred for a further 8 h while the progress of the reaction was monitored by TLC. The mixture was cooled to rt then glacial AcOH (0.16 mmol) was added and stirring was continued at rt for 24 h. The mixture was filtered and the filtrate was concentrated under vacuum to give a crude product that was purified by flash column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow solid; yield: 94.0 mg (77%); mp 164–167 °C. IR (neat): 2966, 2362, 2335, 1772, 1708, 1681, 1436, 1380, 1282 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.01 (d, J = 7.4 Hz, 2 H), 7.89 (d, J = 2.2 Hz, 1 H), 7.62 (s, 1 H), 7.51 (t, J = 7.7 Hz, 2 H), 7.43 (d, J = 6.9 Hz, 2 H), 7.32–7.28 (m, 3 H), 4.80 (s, 2 H), 3.79 (d, J = 2.2 Hz, 2 H). 13C NMR (125 MHz, CDCl3) : δ = 189.45, 173.58, 169.31, 139.50, 137.09, 135.22, 133.88, 128.86, 128.85, 128.60, 128.40, 128.03, 123.17, 42.53, 34.66. HRMS (ES+): m/z [M + H]+ calcd for C19H16NO3: 306.1125; found: 306.1128.
  • 12 Ethyl (2E)-4-Oxo-2-(2-oxo-2-phenylethyl)-4-phenylbut-2-enoate (6aa): Typical Procedure A mixture of α-bromoacetophenone (1a; 119.4 mg, 0.6 mmol) and PS-DMAP (240 mg, 0.72 mmol) in toluene (1 mL) was stirred at 80 °C for 8 h. Keto ester 5a (81.7 mg, 0.4 mmol) and Et3N (55.8 μL, 0.4 mmol) were then added, and the mixture was stirred at 80 °C for 8 h then cooled to rt. Glacial AcOH (0.16 mmol) was added, and the mixture was stirred at rt for 24 h. The mixture was then filtered and the filtrate was concentrated under vacuum to give the crude product that was purified by flash column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow liquid; yield: 100.6 mg (78%). IR (neat): 3064, 2981, 2938, 2842, 1717, 1662, 1600, 1570, 1510, 1445, 1276, 1257, 1215, 1169, 1092 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.05 (s, 1 H), 7.98 (d, J = 7.8 Hz, 4 H), 7.59–7.53 (m, 2 H), 7.49–7.43 (m, 4 H), 4.56 (s, 2 H), 4.30 (q, J = 7.1 Hz, 2 H), 1.30 (t, J = 7.1 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 196.06, 191.73, 166.59, 139.51, 137.45, 136.64, 133.79, 133.31, 133.21, 128.85, 128.73, 128.66, 128.25, 61.95, 38.16, 14.17. HRMS (ES+): m/z [M + H]+ calcd for C20H19O4: 323.1278; found: 323.1274.
  • 13 See the Supporting Information for details.
  • 14 Ethyl 2-Benzoyl-5-phenyl-3-furoate (7aa) A vial was charged with product 6aa (128.9 mg, 0.4 mmol), K2CO3 (82.9 mg, 0.6 mmol), and I2 (10.2 mg, 0.08 mmol). Anhyd DMSO (4 mL) was added, and the mixture was stirred at 80 °C for 1.5 h. After complete consumption of 6aa, the mixture was cooled to rt and extracted with EtOAc. The organic layer was dried (Na2SO4) and purified by flash column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow liquid; yield: 83.3 mg (65%). IR (neat): 2366, 1724, 1652, 1579, 1531, 1479, 1243, 1083 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.99–7.92 (m, 2 H), 7.76 (dd, J = 5.3, 3.3 Hz, 2 H), 7.64–7.59 (m, 1 H), 7.50 (dd, J = 10.8, 4.7 Hz, 2 H), 7.46–7.42 (m, 2 H), 7.40–7.36 (m, 1 H), 7.10 (s, 1 H), 4.12 (q, J = 7.2 Hz, 2 H), 1.08 (t, J = 7.2 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 183.83, 162.88, 156.05, 150.25, 137.48, 133.42, 129.77, 129.53, 129.12, 128.90, 128.62, 125.53, 125.03, 107.48, 61.55, 13.80. HRMS (ES+): m/z [M + H]+ calcd for C20H17O4: 321.1121; found: 321.1109.

Corresponding Author

Nirmal K. Rana
Department of Chemistry, Indian Institute of Technology Jodhpur
Rajashtan-342030
India   

Publication History

Received: 30 May 2022

Accepted after revision: 30 August 2022

Accepted Manuscript online:
30 August 2022

Article published online:
28 September 2022

© 2022. Thieme. All rights reserved

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  • References and Notes

  • 6 Xu J, Fu X, Low R, Goh Y.-P, Jiang Z, Tan C.-H. Chem. Commun. 2008; 5526-5528
    CrossrefPubMed
  • 10 During our initial optimization of the reaction conditions, we found that a minimum of 1.8 equivalents (based on DMAP content) of PS-DMAP (~3.0 mmol/g DMAP loading; matrix crosslinked with 2% divinylbenzene) is essential for effective formation of the pyridinium salt.
  • 11 (3E)-1-Benzyl-3-(2-oxo-2-phenylethylidene)pyrrolidine-2,5-dione (4aa); Typical Procedure A mixture of α-bromoacetophenone (1a; 119.4 mg, 0.6 mmol) and PS-DMAP (240 mg, 0.72 mmol) in toluene (1 mL) was stirred at 80 °C for 8 h. After complete consumption of 1a, N-benzylmaleimide (3a;74.8 mg, 0.4 mmol) and Et3N (55.8 μL, 0.4 mmol) were added, and the mixture was stirred for a further 8 h while the progress of the reaction was monitored by TLC. The mixture was cooled to rt then glacial AcOH (0.16 mmol) was added and stirring was continued at rt for 24 h. The mixture was filtered and the filtrate was concentrated under vacuum to give a crude product that was purified by flash column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow solid; yield: 94.0 mg (77%); mp 164–167 °C. IR (neat): 2966, 2362, 2335, 1772, 1708, 1681, 1436, 1380, 1282 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.01 (d, J = 7.4 Hz, 2 H), 7.89 (d, J = 2.2 Hz, 1 H), 7.62 (s, 1 H), 7.51 (t, J = 7.7 Hz, 2 H), 7.43 (d, J = 6.9 Hz, 2 H), 7.32–7.28 (m, 3 H), 4.80 (s, 2 H), 3.79 (d, J = 2.2 Hz, 2 H). 13C NMR (125 MHz, CDCl3) : δ = 189.45, 173.58, 169.31, 139.50, 137.09, 135.22, 133.88, 128.86, 128.85, 128.60, 128.40, 128.03, 123.17, 42.53, 34.66. HRMS (ES+): m/z [M + H]+ calcd for C19H16NO3: 306.1125; found: 306.1128.
  • 12 Ethyl (2E)-4-Oxo-2-(2-oxo-2-phenylethyl)-4-phenylbut-2-enoate (6aa): Typical Procedure A mixture of α-bromoacetophenone (1a; 119.4 mg, 0.6 mmol) and PS-DMAP (240 mg, 0.72 mmol) in toluene (1 mL) was stirred at 80 °C for 8 h. Keto ester 5a (81.7 mg, 0.4 mmol) and Et3N (55.8 μL, 0.4 mmol) were then added, and the mixture was stirred at 80 °C for 8 h then cooled to rt. Glacial AcOH (0.16 mmol) was added, and the mixture was stirred at rt for 24 h. The mixture was then filtered and the filtrate was concentrated under vacuum to give the crude product that was purified by flash column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow liquid; yield: 100.6 mg (78%). IR (neat): 3064, 2981, 2938, 2842, 1717, 1662, 1600, 1570, 1510, 1445, 1276, 1257, 1215, 1169, 1092 cm–1. 1H NMR (500 MHz, CDCl3): δ = 8.05 (s, 1 H), 7.98 (d, J = 7.8 Hz, 4 H), 7.59–7.53 (m, 2 H), 7.49–7.43 (m, 4 H), 4.56 (s, 2 H), 4.30 (q, J = 7.1 Hz, 2 H), 1.30 (t, J = 7.1 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 196.06, 191.73, 166.59, 139.51, 137.45, 136.64, 133.79, 133.31, 133.21, 128.85, 128.73, 128.66, 128.25, 61.95, 38.16, 14.17. HRMS (ES+): m/z [M + H]+ calcd for C20H19O4: 323.1278; found: 323.1274.
  • 13 See the Supporting Information for details.
  • 14 Ethyl 2-Benzoyl-5-phenyl-3-furoate (7aa) A vial was charged with product 6aa (128.9 mg, 0.4 mmol), K2CO3 (82.9 mg, 0.6 mmol), and I2 (10.2 mg, 0.08 mmol). Anhyd DMSO (4 mL) was added, and the mixture was stirred at 80 °C for 1.5 h. After complete consumption of 6aa, the mixture was cooled to rt and extracted with EtOAc. The organic layer was dried (Na2SO4) and purified by flash column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow liquid; yield: 83.3 mg (65%). IR (neat): 2366, 1724, 1652, 1579, 1531, 1479, 1243, 1083 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.99–7.92 (m, 2 H), 7.76 (dd, J = 5.3, 3.3 Hz, 2 H), 7.64–7.59 (m, 1 H), 7.50 (dd, J = 10.8, 4.7 Hz, 2 H), 7.46–7.42 (m, 2 H), 7.40–7.36 (m, 1 H), 7.10 (s, 1 H), 4.12 (q, J = 7.2 Hz, 2 H), 1.08 (t, J = 7.2 Hz, 3 H). 13C NMR (125 MHz, CDCl3): δ = 183.83, 162.88, 156.05, 150.25, 137.48, 133.42, 129.77, 129.53, 129.12, 128.90, 128.62, 125.53, 125.03, 107.48, 61.55, 13.80. HRMS (ES+): m/z [M + H]+ calcd for C20H17O4: 321.1121; found: 321.1109.

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Zoom Image
Scheme 1 Substrate scope of the PS-DMAP-mediated reactions of in-situ-generated N-ylides with N-substituted maleimides. Reagents and conditions: 1 (0.6 mmol), 3 (0.4 mmol), PS-DMAP (240 mg), toluene (1 mL), Et3N (0.4 mmol), AcOH (0.16 mmol). The reported reaction times are those taken to consume the maleimide 3, as monitored by TLC.
Zoom Image
Figure 1 Detection of intermediate cycloadduct by HRMS of the crude reaction mixture
Zoom Image
Scheme 2 Gram-scale reactions and recycling of PS-DMAP
Zoom Image
Scheme 3 DMAP-mediated formal addition/elimination reactions
Zoom Image
Scheme 4 Synthetic modification of a functionalized olefin to a trisubstituted furan