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Synlett 2011(5): 674-678  
DOI: 10.1055/s-0030-1259554
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 3-Aryl-3-pyrrolines and 3-Arylpyrroles via Spontaneous Rearrangement of N-Sulfinyl 2-Aryl-2-vinylaziridines

Erika Leemans, Filip Colpaert, Sven Mangelinckx, Stijn De Brabandere, Bram Denolf, Norbert De Kimpe*
Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium
Fax: +32(9)2646221; e-Mail: norbert.dekimpe@ugent.be;
Further Information

Publication History

Received 10 January 2011
Publication Date:
11 February 2011 (online)

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Abstract

Addition of vinylmagnesium bromide across chiral α-chloro N-tert-butanesulfinyl ketimines afforded 3-aryl-1-(tert-butanesulfinyl)-3-pyrrolines in high yield (65-91%) after purification by means of recrystallization from diethyl ether. The synthesis of these 3-aryl-3-pyrrolines is explained by initial formation of 2-aryl-2-vinylaziridines which spontaneously rearrange via carbon-nitrogen bond cleavage to form stabilized 1,3-dipolar intermediates which in turn ring closed to 3-pyrrolines.

Key words

aziridines - rearrangement - heterocycles - imines - pyrrolines

1

Postdoctoral Fellow of the Research Foundation-Flanders (FWO).

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Synthesis of ( R S )- N - tert -Butanesulfinyl 3-Phenyl-3-pyrroline (4a) α-Chloro imine 5a (0.91 mmol) was dissolved in dry CH2Cl2 (10 mL), and the stirred solution was cooled to -78 ˚C. Two equiv of vinylmagnesium bromide (1 M solution in THF, 1.82 mL, 1.82 mmol) were added to the solution, and the reaction mixture was allowed to stir for 2 h at -78 ˚C before being left at -40 ˚C for 4 h. The reaction mixture was quenched at this temperature by the addition of aq NH4Cl (5 mL) and immediately extracted with CH2Cl2 (2 × 10 mL). The organic layers were dried (MgSO4, containing little of K2CO3), filtered, and concentrated. The mixture was purified by means of recrystallization from Et2O to afford the pyrroline 4a in 91% yield. Colorless crystals; mp 55.6 ± 0.5 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.50 (9 H, s), 3.39 (1 H, dddd, J = 15.8, 5.5, 4.1, 1.4 Hz), 3.85 (1 H, dddd, J = 15.8, 4.3, 3.3, 3.3 Hz), 4.25 (1 H, dddd, J = 18.4, 3.3, 1.7, 1.7 Hz), 4.40 (1 H, dddd, J = 18.4, 4.4, 4.4, 1.7 Hz), 5.99-6.03 (1 H, m), 7.28-7.37 (5 H, m). ¹³C NMR (75 MHz, CDCl3): δ = 22.1, 36.9, 48.3, 55.4, 112.6, 125.4, 128.1, 128.6, 135.3, 139.1. MS (ES, pos. mode): m/z (%) = 194 (100) [M - t-Bu + 2H]+. IR (KBr): νmax = 1042, 1085, 1364, 1453, 2962 cm-¹. Anal. Calcd for C14H19NOS: C, 67.43; H, 7.68; N, 5.62. Found: C, 67.17; H, 7.84; N, 5.33. [α]D -28.3 (c 1.03, CH2Cl2).

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( R s , S )-1-( tert -Butanesulfinyl)-2-isopropenyl-2-phenylaziridine [( R s ,S )-6] Yellow crystals; mp 54.2 ± 0.5 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.21 (9 H, s), 1.65 (3 H, s), 2.11 (1 H, s), 3.23 (1 H, s), 4.95 (1 H, s), 5.14 (1 H, s), 7.26-7.47 (5 H, m). ¹³C NMR (75 MHz, CDCl3): δ = 19.8, 22.8, 30.3, 51.1, 57.4, 112.9, 128.3, 128.5, 129.7, 134.9, 145.4. MS (ES, pos. mode): m/z (%) = 264 (100) [M + H]+. IR (ATR): νmax = 696, 1074, 1447, 2961 cm-¹. Anal. Calcd for C15H21NOS: C, 68.40; H, 8.04; N, 5.32. Found: C, 68.04; H, 8.24; N, 5.12. R f  = 0.28 (PE-EtOAc = 3:1). [α]D -394.7 (c 1.03, CH2Cl2).

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( R S )- N - tert -Butanesulfinyl 2-Methyl-4-phenyl-3-pyrroline (9)
Spectroscopic data of the major diastereomer obtained from the mixture of diastereomers 9 (dr 86:14). Brown oil. ¹H NMR (300 MHz, CDCl3): δ = 1.51 (9 H, s), 1.53 (3 H, d, J = 6.6 Hz), 3.88-3.98 (1 H, m), 4.20 (1 H, ddd, J = 18.4, 3.0, 1.4 Hz), 4.39 (1 H, ddd, J = 18.4, 4.1, 1.9 Hz), 5.70-5.72 (1 H, m), 7.27-7.37 (5 H, m). ¹³C NMR (75 MHz, CDCl3):
δ = 19.2, 24.5, 42.9, 46.2, 60.9, 122.1, 125.7, 127.9, 128.6, 139.3, 139.8. MS (ES, pos. mode): m/z (%) = 264 (100)
[M + H]+. IR (ATR): νmax = 694, 1050, 1447, 2926 cm-¹. Anal. Calcd for C15H21NOS: C, 68.40; H, 8.04; N, 5.32. Found: C, 68.69; H, 7.99; N, 5.49.

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Synthesis of ( R S )- N -( tert -Butanesulfinyl) 3-(4-Methoxy-phenyl)pyrrole (13e)
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (0.042 g, 0.18 mmol) was dissolved in 1,4-dioxane (10 mL) and the mixture added dropwise to a solution of (R S )-N-(tert-butanesulfinyl)-3-(4-methoxyphenyl)-3-pyrroline (4e, 0.057 g, 0.20 mmol) in 1,4-dioxane (10 mL). After stirring for 16 h at r.t., the reaction mixture was quenched by the addition of a 10% solution of NaHSO3 (5 mL) and immediately extracted with EtOAc (2 × 10 mL). The organic layers were dried (MgSO4), filtered, and concentrated. The compound was purified by means of column chromatography to afford (R S )-N-(tert-butanesulfinyl) 3-(4-methoxyphenyl)pyrrole (13e, 0.049 g) in 87% yield; black crystals; mp 133.6 ± 0.5 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.45 (9 H, s), 3.82 (3 H, s), 5.86 (1 H, dd, J = 9.9, 1.7 Hz), 6.89-6.93 (2 H, m), 7.22-7.26 (2 H, m), 7.53 (1 H, dd, J = 9.9, 2.2 Hz), 7.68-7.70 (1 H, m). ¹³C NMR (75 MHz, CDCl3): δ = 23.2, 55.4, 62.1, 88.8, 113.8, 114.3, 126.6, 131.4, 139.8, 144.9, 158.2. MS (ES, pos. mode): m/z (%) = 278 (100) [M + H]+. IR (ATR): νmax = 1187, 1367, 1591, 2928 cm-¹. Anal. Calcd for C15H19NO2S: C, 64.95; H, 6.90; N, 5.05. Found: C, 65.07; H, 6.64; N, 4.89. R f  = 0.29 (PE-EtOAc = 3:1). [α]D = 28.7 (c 0.09, CH2Cl2).

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Synthesis of 3,4-Dibromo-3-phenylpyrrolidine (14)
A solution of (R S )-N-(tert-butanesulfinyl)-3-phenyl-3-pyrroline (4a, 0.1 g, 0.40 mmol) in dry CH2Cl2 (10 mL) was cooled to 0 ˚C and Br2 (1.05 equiv, 0.023 mL, 0.42 mmol) was added dropwise. After stirring for 1 h, Et3N (1 equiv, 0.06 mL, 0.40 mmol) was added, and the reaction mixture was allowed to stir for another 30 min at r.t. H2O (10 mL) was added, and the reaction mixture was immediately extracted with CH2Cl2 (2 × 10 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated. The compound was purified by means of column chromatography (R f  = 0.18; PE-EtOAc = 3:1) to afford 3,4-dibromo-3-phenylpyrrolidine (14, 0.04 g) in 33% yield. Light brown oil. ¹H NMR (300 MHz, CDCl3): δ = 3.73 (1 H, dd, J = 14.9, 3.3 Hz), 3.91-3.99 (1 H, m), 4.35 (1 H, dd, J = 15.1, 4.1 Hz), 4.62 (1 H, dd, J = 15.4, 11.6 Hz), 5.11-5.23 (2 H, m), 7.38-7.48 (5 H, m). ¹³C NMR (75 MHz, CDCl3): δ = 49.9, 50.8, 53.0, 66.3, 126.2, 129.1, 129.6, 140.0. IR (ATR): νmax = 1156, 1337, 2359, 3271 cm-¹. Anal. Calcd for C10H11Br2N: C, 39.38; H, 3.64; N, 4.59. Found: C, 39.03; H, 3.88; N, 4.21.