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Synlett 2007(19): 2995-2998  
DOI: 10.1055/s-2007-990886
LETTER
© Georg Thieme Verlag Stuttgart · New York

Preparation of Unsaturated Aminonitriles from the Aza-Morita-Baylis-Hillman Reactions of Aldimines with Penta-2,4-dienenitrile

Kristen N. Clary, Thomas G. Back*
Department of Chemistry, University of Calgary, Calgary, AB, T2N 1N4, Canada
Fax: +1(403)2899488; e-Mail: tgback@ucalgary.ca ;
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Publication History

Received 8 August 2007
Publication Date:
08 November 2007 (online)

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Abstract

N-(Phenylsulfonyl)aldimines undergo facile aza-Morita-Baylis-Hillman reactions with penta-2,4-dienenitrile in anhydrous DMF in the presence of catalytic 3-hydroxyquinuclidine and methanol to afford the corresponding unsaturated aminonitriles.

Key words

aza-Morita-Baylis-Hillman reaction - penta-2,4-dienenitrile - conjugated diene - N-(phenylsulfonyl)aldimines - unsaturated aminonitriles

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Preparation of Penta-2,4-dienenitrile (5)
Potassium tert-butoxide (11.76 g, 104.8 mmol) in anhydrous THF (150 mL) was added dropwise to diethyl cyano­-methylphosphonate (16.95 g, 95.76 mmol) in anhydrous THF (180 mL) at -78 °C. After 30 min, freshly distilled acrolein (6.00 g, 108 mmol) was added dropwise. The reaction mixture was stirred for 20 min and then warmed to r.t. and quenched with sat. aq NH4Cl solution. The solution was extracted with Et2O, washed with brine and H2O, and dried (MgSO4). The combined organic layers were concentrated on a rotary evaporator at r.t. and the residue was chromatographed on neutral alumina (hexanes-Et2O, 3:1) to afford 5 (3.974 g, 53%) as a mixture of E/Z isomers (80:20, determined by NMR integration). 1H NMR (300 MHz, CDCl3): δ (E-isomer) = 7.00 (dd, J = 15.9, 10.8 Hz, 1 H), 6.42 (dt, J = 16.9, 10.8 Hz, 1 H), 5.61 (d, J = 16.9 Hz, 1 H), 5.55 (d, J = 10.2 Hz, 1 H); δ (Z-isomer) = 7.24 (d, J = 6.7 Hz, 1 H), 7.17 (d, J = 7.2 Hz, 1 H), 6.83 (dt, J = 10.3, 5.1 Hz, 1 H).

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Typical Procedure - Preparation of Phenyl Derivative 6a A solution of nitrile 5 (0.024 mL, 20.8 mg, 0.26 mmol), imine 1a (64 mg, 0.26 mmol), MeOH (60 µL, 1.5 mmol), and HQD (8.6 mg, 0.068 mmol) in 4 mL of anhydrous DMF was stirred for 8 h at r.t. The reaction mixture was diluted with Et2O and washed with H2O and brine. The organic layer was dried (MgSO4), concentrated, and chromatographed (toluene-EtOAc,16:1). The product was recrystallized from CHCl3-hexanes to afford 66 mg (79%) of the pure Z-isomer: white needles; mp 156-157 °C. IR (film): 3243, 2208, 1317, 1165 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.82 (d, J = 7.2 Hz, 2 H), 7.57 (m, 1 H), 7.47 (m, 2 H), 7.32-7.29 (m, 3 H), 7.18-7.15 (m, 2 H), 6.80 (d, J = 10.8 Hz, 1 H), 6.60 (dt, J = 16.4, 10.5 Hz, 1 H), 5.59 (d, J = 16.9 Hz, 1 H), 5.57 (d, J = 9.2 Hz, 1 H), 5.30 (d, J = 7.2 Hz, exchanged with D2O, 1 H), 5.15 (d, J = 7.2 Hz, collapsed to s with D2O, 1 H). 13C NMR (75 MHz, CDCl3): δ = 145.6, 140.1, 136.7, 133.2, 132.2, 129.4, 129.3, 129.2, 127,6, 127.5, 126.9, 115.4, 114.2, 59.9. MS: m/z (%) = 324 (2), 183 (51), 77 (100). HRMS: m/z calcd for C18H16N2O2S: 324.0933; found: 324.0939.
p-Chlorophenyl derivative 6b: white needles; mp 173-174 °C. IR (film): 3243, 2213, 1309, 1170 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.82 (d, J = 7.2 Hz, 2 H), 7.59-7.46 (m, 2 H), 7.31-7.25 (m, 3 H), 7.12 (d, J = 8.7 Hz, 2 H), 6.77 (d, J = 10.8 Hz, 1 H), 6.58 (dt, J = 16.4, 10.3 Hz, 1 H), 5.61 (d, J = 16.4 Hz, 1 H), 5.60 (d, J = 7.2 10.2 Hz, 1 H), 5.15 (d, J = 7.2 Hz, collapsed to s with D2O, 1 H), 5.05 (d, J = 7.2 Hz, exchanged with D2O, 1 H). 13C NMR (75 MHz, CDCl3): δ = 146.0, 139.9, 135.3, 135.1, 133.4, 132.0, 129.6, 129.3, 128.3, 128.1, 127.4, 115.2, 113.6, 59.4. MS: m/z (%) = 358 (4) [M+], 217 (78), 76 (100). HRMS: m/z calcd for C18H15ClN2O2S: 358.0543; found: 358.0520.
m-Chlorophenyl derivative 6c: off-white solid; mp 114-119 °C. IR (film): 3259, 2210, 1337, 1162 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.79 (d, J = 7.2 Hz, 2 H), 7.58-7.43 (m, 3 H), 7.27-7.17 (m, 2 H), 7.10-7.06 (m, 2 H), 6.77 (d, J = 10.8 Hz, 1 H), 6.57 (dt, J = 16.4, 10.8 Hz, 1 H), 5.69 (d, J = 7.7 Hz, exchanged with D2O, 1 H), 5.59 (d, J = 16.4 Hz, 1 H), 5.58 (d, J = 10.8 Hz, 1 H), 5.14 (d, J = 7.7 Hz, collapsed to s with D2O, 1 H). 13C NMR (75 MHz, CDCl3): δ = 146.1, 139.9, 138.6, 135.2, 133.3, 132.0, 130.6, 129.3, 129.2, 128.2, 127.35, 127.25, 125.1, 115.3, 113.5, 59.3. MS: m/z (%) = 358 (5) [M+], 217 (100), 141 (33), 77 (72). HRMS: m/z calcd for C18H15ClN2O2S: 358.0543; found: 358.0556.
o-Chlorophenyl derivative 6d: white solid; mp 137-141 °C. IR (film): 3266, 2217, 1337, 1175 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.80 (d, J = 7.2Hz, 2 H), 7.55-7.41 (m, 3 H), 7.33-7.21 (m, 4 H), 6.82 (d, J = 10.8 Hz, 1 H), 6.63 (dt, J = 16.4, 10.2 Hz, 1 H), 5.66-5.58 (m, 3 H), 5.36 (d, J = 7.7 Hz, exchanged with D2O, 1 H). 13C NMR (75 Hz, CDCl3): δ = 146.0, 139.8, 134.1, 133.1, 132.8, 132.2, 130.3, 130.2, 129.2, 128.7, 127.9, 127.7, 127.3, 115.3, 113.2, 56.6. MS: m/z (%) = 358 (3) [M+], 217 (100), 141 (22), 77 (47). HRMS: m/z calcd for C18H15ClN2O2S: 358.0543; found: 358.0554.
p-Cyanophenyl derivative 6e: white solid; mp 149-152 °C. IR (film): 3252, 2226, 1335, 1165 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.78 (d, J = 7.2 Hz, 2 H), 7.59-7.54 (m, 3 H), 7.47-7.42 (m, 2 H), 7.39-7.27 (m, 2 H), 6.73 (d, J = 11.3 Hz, 1 H), 6.55 (dt, J = 16.9, 10.3 Hz, 1 H), 5.97 (d, J = 8.2 Hz, exchanged with D2O, 1 H), 5.62-5.57 (m, 2 H), 5.23 (d, J = 7.7 Hz, collapsed to s with D2O, 1 H). 13C NMR (75 MHz, CDCl3): δ = 146.6, 141.7, 139.9, 133.4, 132.9, 131.9, 129.4, 128.8, 127.8, 127.3, 118.2, 115.1, 112.9, 112.8, 59.4. MS: m/z (%) = 349 (2) [M+], 208 (100), 141 (26), 77 (52). HRMS: m/z calcd for C13H10N3 [M+ - C6H5SO2]: 208.0875; found: 208.0859.
p-Methoxyphenyl derivative 6f: off-white solid; mp 139-142 °C. IR (film): 3252, 2210, 1316, 1163 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.82 (d, J = 7.2 Hz, 2 H), 7.60-7.56 (m, 1 H), 7.51-7.46 (m, 2 H), 7.07 (d, J = 8.7 Hz, 2 H), 6.83-6.79 (m, 3 H), 6.60 (dt, J = 16.4, 10.3 Hz, 1 H), 5.58 (d, J = 16.9 Hz, 1 H), 5.56 (d, J = 9.7 Hz, 1 H), 5.14-5.07 (m, 2 H, collapsed to s, 1 H, with D2O), 3.78 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 160.1, 145.3, 140.1, 133.2, 132.2, 129.3, 128.7, 128.2, 127.5, 127.4, 115.6, 114.7, 114.5, 59.4, 55.5. MS: m/z (%) = 354 (4) [M+], 276 (12), 213 (44), 77 (100). HRMS: m/z calcd for C19H18N2O3S: 354.1038; found: 354.1020.
p-Carbomethoxy derivative 6g: white solid; mp 127-131 °C. IR (film): 3266, 2217, 1714, 1337, 1281, 1162 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.97 (d, J = 8.2 Hz, 2 H), 7.82 (d, J = 7.2 Hz, 1 H), 7.60-7.55 (m, 1 H), 7.50-7.45 (m, 2 H), 7.25-7.22 (m, 2 H), 6.78 (d, J = 11.3 Hz, 1 H), 6.58 (dt, J = 16.4, 10.8 Hz, 1 H), 5.61 (d, J = 16.4 Hz, 1 H), 5.60 (d, J = 10.3 Hz, 1 H), 5.37 (d, J = 7.7 Hz, exchanged with D2O, 1 H), 5.22 (d, J = 7.7 Hz, collapsed to s with D2O, 1 H), 3.92 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 166.4, 146.2, 141.3, 140.0, 133.4, 132.0, 130.9, 130.6, 129.3, 128.2, 127.4, 127.0, 115.2, 113.5, 59.6, 52.5. MS: m/z (%) = 382 (1) [M+], 157 (13), 141 (16), 76 (100). HRMS: m/z calcd for C20H18O4N2S: 382.0987; found: 382.0955.
o-Carbomethoxy derivative 6h: white solid; mp 127-132 °C. IR (film): 3283, 2217, 1713, 1270, 1165 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.86 (d, J = 6.7 Hz, 1 H), 7.72 (d, J = 7.7 Hz, 2 H), 7.46-7.27 (m, 6 H), 6.82 (d, J = 10.3 Hz, 1 H), 6.63 (dt, J = 16.9, 10.8 Hz, 1 H), 6.58 (d, J = 9.3 Hz, exchanged with D2O, 1 H), 5.80 (d, J = 9.2 Hz, collapsed to s with D2O, 1 H), 5.56 (d, J = 16.4 Hz, 1 H), 5.54 (d, J = 9.8 Hz, 1 H), 3.85 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 168.0, 145.3, 140.4, 138.1, 133.1, 132.8, 132.4, 131.8, 130.4, 129.0, 128.5, 128.3, 127.3, 127.1, 115.6, 113.9, 57.7, 52.9. MS: m/z (%) = 382 (0.1) [M+], 286 (52), 241 (16), 209 (39), 77 (100). HRMS: m/z calcd for C14H13N2O2 [M+ - PhSO2]: 241.0977; found: 241.0974.
3-Pyridyl derivative 6i: white solid; mp 189-191 °C. IR (film): 2225, 1330, 1162 cm-1. 1H NMR (300 MHz, acetone-d 6): δ = 8.54 (d, J = 2.0 Hz, 1 H), 8.49 (dd, J = 4.6, 1.6 Hz, 1 H), 8.41-8.06 (m, 5 H), 7.76-7.73 (m, 1 H), 7.34-7.29 (m, 1 H), 7.03 (d, J = 11.3 Hz, 1 H), 6.61 (dt, J = 16.9,10.3 Hz, 1 H), 5.74 (d, J = 16.4 Hz, 1 H), 5.65 (d, J = 9.7 Hz, 1 H), 5.54 (s, 1 H). 13C NMR (75 MHz, acetone-d 6): δ = 151.0, 150.7, 149.6, 147.4, 146.8, 135.4, 133.6, 132.9, 129.4, 128.6, 125.1, 124.4, 115.9, 115.1, 58.3. MS: m/z (%) = 184 (100), 122 (24). HRMS: m/z calcd for C11H10N3 [M+ - PhSO2]: 184.0875; found: 184.0875.
2-Furanyl derivative 6j: off-white solid; mp 119-121 °C. IR (film): 3238, 2210, 1329, 1162 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.85-7.81 (m, 2 H), 7.60-7.46 (m, 3 H), 7.31 (dd, J = 1.8, 0.8 Hz, 1 H), 6.80 (d, J = 11.1 Hz, 1 H), 6.61 (dt, J = 16.6, 10.5 Hz, 1 H), 6.28 (dd, J = 3.3, 1.9 Hz, 1 H), 6.22 (d, J = 3.4 Hz, 1 H), 5.64 (d, J = 16.9 Hz, 1 H), 5.61 (d, J = 9.8 Hz, 1 H), 5.32 (d, J = 8.0 Hz, exchanged with D2O, 1 H), 5.25 (d, J = 8.0 Hz, collapsed to s with D2O, 1 H). 13C NMR (50 MHz, CDCl3): δ = 148.4, 145.9, 143.4, 139.9, 133.0, 131.9, 129.0, 127.8, 127.1, 114.9, 112.0, 110.7, 108.8, 53.9. MS: m/z (%) = 236 (10), 173 (100). HRMS: m/z calcd for C10H9N2O [M+ - PhSO2]: 173.0715; found: 173.0723.
1-Naphthyl derivative 6k: colorless crystals; mp 130-131 °C. IR (film): 3269, 2212, 1325, 1160 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.85-7.76 (m, 5 H), 7.56-7.31 (m, 7 H), 6.83 (d, J = 11.0 Hz, 1 H), 6.62 (dt, J = 16.5, 10.7 Hz, 1 H), 5.92 (d, J = 6.7 Hz, 1 H, collapsed to s with D2O), 5.52 (d, J = 9.7 Hz, 1 H), 5.50, (d, J = 16.7 Hz, 1 H), 5.28 (d, J = 6.7 Hz, exchanged with D2O, 1 H). 13C NMR (75 MHz, CDCl3): δ = 145.7, 139.9, 134.1, 133.0, 132.1, 130.0, 129.2, 129.0, 127.33, 127.26, 126.3, 125.5, 125.2, 122.3, 115.6, 114.1, 56.0. MS: m/z (%) = 375 (15), 374 (60), 233 (100), 217 (57), 154 (75), 77 (67). HRMS: m/z calcd for C16H13N2 [M+ - PhSO2]: 233.1079; found: 233.1099.