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Synlett 2009(13): 2172-2176  
DOI: 10.1055/s-0029-1217569
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of the Disubstituted Maleic Anhydride Frame Using a Novel Tandem Radical-Polar Reaction

Mariella Pattarozzi*a, Franco Ghelfia, Fabrizio Roncagliaa, Ugo M. Pagnonia, Andrew F. Parsonsb
a Dipartimento di Chimica, Università degli Studi di Modena e Reggio Emilia, via Campi 183, 41100 Modena, Italy
Fax: +39(059)373543; e-Mail: mariella.pattarozzi@unimore.it;
b Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
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Publication History

Received 28 April 2009
Publication Date:
15 July 2009 (online)

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Abstract

An unreported 5-endo-trig atom-transfer radical cyclization of cyclic N-α-dichloroacyl-ketene-N,S-acetals, which evolves as a tandem radical-polar process, is described. The reaction, which is carried out in the presence of a Cu(I) complex catalyst (10 mol%) and an inorganic base (i.e., carbonate), can be exploited as the key step for a novel, short, and versatile synthesis of the 3,4-disubstituted maleic anhydride nucleus.

Key words

cyclizations - imides - radical reactions - sulfur - tandem reactions

    References and Notes

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18

3-(2,2-Dichlorobutanoyl)-2-ethylidene-1,3-thiazolidine (5a)
Yellow oil. R f  = 0.64 (PE-Et2O, 1:1). ¹H NMR (200 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3 H, CH3), 1.74 (d, J = 6.8 Hz, 3 H, CH3), 2.50 (q, J = 7.1 Hz, 2 H, CH2), 3.05 (t, J = 6.2 Hz, 2 H, CH2), 4.48 (t, J = 6.2 Hz, 2 H, CH2), 6.26 (q, J = 7.1 Hz, 1 H, CH) ppm. ¹³C NMR (50 MHz, CDCl3): δ = 9.6, 15.8, 28.1, 39.4, 53.1, 87.2, 109.1, 135.0, 162.3 ppm. MS (EI, 70 eV): m/z (%) = 253 (22) [M]+, 218 (100), 190 (28). IR (film): 1670 (C=O) cm-¹.
3-(2,2-Dichlorobutanoyl)-2-ethylidene-1,3-thiazine (5b)
Yellowish oil. R f  = 0.56 (PE-Et2O, 1:1). ¹H NMR (400 MHz, CDCl3): δ = 1.19 (t, J = 7.1 Hz, 3 H, CH3), 1.84 (d, J = 6.8 Hz, 3 H, CH3), 2.08 (br m, 2 H, CH2), 2.49 (q, J = 7.1 Hz, 2 H, CH2), 2.85 (br m, 2 H, CH2), 4.22 (br m, 2 H, CH2), 6.07 (br m, 1 H, CH) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 9.7, 14.4, 26.3, 29.5, 40.1, 49.8, 85.7, 130.6, 132.2, 163.5 ppm. MS (EI, 70 eV): m/z (%) = 267 (2) [M]+, 232 (42), 156 (96), 128 (100). IR (film): 1669 (C=O) cm-¹.

20

Typical Procedure for the ATRC
Compound 5b (2 mmol, 536 mg), CuCl (10 mol%, 20 mg), and Na2CO3 (2 mmol, 212 mg) were weighed into a Schlenk tube, then dry MeCN (3 mL) and TMEDA (20 mol%, 60 µL) were added under Ar. The mixture was stirred at 30 ˚C and after 17 h diluted with H2O and extracted with CH2Cl2 (3 × 25 mL). The combined organic layers were concentrated under vacuum. Chromatography of the crude product on silica, eluting with a PE-Et2O gradient from 9:1 to 4:6, afforded 1-{3-[(7-ethyl-8-methyl-6-oxo-3,4-dihydro-2H-pyrrolo[2,1-b][1,3]thiazin-6 (8aH)-yl)sulfanyl]propyl}-3-ethyl-4-methyl-1H-pyrrole-2,5-dione (13b) as yellow oil (327 mg, 80%) and 1,1′-(disulfanediyldipropane-2,1-diyl)bis(3-ethyl-4-methyl-1H-pyrrole-2,5-dione) (14b) as orange oil (60 mg, 14%).
Compound 13b: R f  = 0.12 (PE-Et2O, 1:1). ¹H NMR (400 MHz, CDCl3): δ = 0.92 (t, J = 7.6 Hz, 3 H, CH3), 0.98 (t, J = 7.6 Hz, 3 H, CH3), 1.44 (q t, J = 13.2 Hz, 3.0 Hz, 1 H, CHaxH), 1.51 (quin, J = 7.0 Hz, 2 H, CH2), 1.62-1.77 (m, 2 H, CH2), 1.78-1.90 (m, 1 H, CHeqH), 1.80 (s, 3 H, CH3), 1.88 (s, 3 H, CH3), 2.17 (q, J = 7.6 Hz, 2 H, CH2), 2.24 (q, J = 7.6 Hz, 2 H, CH2), 2.54 (br d t, J = 13.2 Hz, 1 H, CHeqH), 2.94 (t d, J = 13.2, 3.0 Hz, 1 H, CHaxH), 3.17 (t d, J = 13.2, 3.0 Hz, 1 H, CHaxH), 3.29 (t, J = 7.0 Hz, 2 H, CH2), 4.11 (br d, J = 13.2 Hz, 1 H, CHeqH) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 8.4, 10.2, 12.6, 13.1, 17.0, 26.2, 26.8, 27.7, 27.9, 35.6, 37.0, 73.8, 134.5, 136.5, 142.1, 150.1, 167.6, 171.6, 172.1 ppm. HRMS: m/z calcd for C20H28N2NaO3S2 [M + Na]+ 431.1434; found: 431.1438. IR (film): 1685 (C=O) cm-¹.
Compound 14b: R f  = 0.33 (PE-Et2O, 1:1). ¹H NMR (400 MHz, CDCl3): δ = 1.12 (t, J = 7.6 Hz, 6 H, 2 CH3), 1.90-2.00 (m, 4 H, 2 CH2), 1.95 (s, 6 H, 2 CH3), 2.39 (q, J = 7.6 Hz, 4 H, 2 CH2), 2.64 (t, J = 7.0 Hz, 4 H, 2 CH2), 3.56 (t, J = 7.0 Hz, 4 H, 2 CH2) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 8.5, 12.6, 17.1, 28.3, 36.0, 36.7, 136.5, 142.2, 171.8, 172.2 ppm. HRMS: m/z calcd for C20H28N2NaO4S2 [M+Na]+: 447.1383; found: 447.1385. IR (film): 1700 (C=O) cm-¹.
All other compounds show spectral data (¹H NMR, ¹³C NMR, HRMS, and IR) consistent with their structures.

22

1-[3-({[3-(3-Ethyl-4-methyl-2,5-dioxo-2,5-dihydro-1 H -pyrrol-1-yl)propyl]sulfonyl}sulfanyl)propyl]-3-ethyl-4-methyl-1 H -pyrrole-2,5-dione (17)
Yellow oil. R f  = 0.10 (PE-Et2O, 1:1). ¹H NMR (400 MHz, CDCl3): δ = 1.11 (t, J = 7.6, 6 H, 2 CH3), 1.94 (s, 6 H,2 CH3), 2.00 (quin, J = 6.8 Hz, 2 H, CH2), 2.14 (quin, J = 7.2 Hz, 2 H, CH2), 2.38 (br q, J = 7.6 Hz, 4 H, 2 CH2), 3.07 (br t, J = 6.8 Hz, 2 H, CH2), 3.31 (br t, J = 7.2 Hz, 2 H, CH2), 3.57 (br t, J = 6.8 Hz, 2 H, CH2), 3.61 (br t, J = 7.2 Hz, 2 H, CH2) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 8.4, 12.5, 17.0, 23.4, 28.9, 33.5, 35.8, 36.1, 60.2, 136.6, 136.7, 142.28, 142.32, 171.6, 171.7, 172.0, 172.1 ppm. HRMS: m/z calcd for C20H29N2O6S2 [M + H]+: 457.1462; found: 457.1470. IR (film): 1700 (C=O) cm-¹.