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Synlett 2003(7): 0947-0950
DOI: 10.1055/s-2003-39325
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Silver Acetate Catalysed Asymmetric 1,3-Dipolar Cycloadditions of Imines and Chiral Acrylamides

Miklós Nyerges*a, David Bendellb, Andrea Aranyb, David E. Hibbsc, Simon J. Colesd, Michael B. Hursthoused, Paul W. Groundwaterb, Otto Meth-Cohnb
a Research Group of the Hungarian Academy of Sciences, Department of Organic Chemical Technology, Technical University of Budapest, 1521 Budapest P.O.B. 91, Hungary
e-Mail: mnyerges@mail.bme.hu;
b Institute of Pharmacy and Chemistry, School of Sciences, University of Sunderland, Sunderland, SR1 3SD, UK
c Department of Chemistry, Cardiff University, P.O. Box 912, Cardiff, CF1 3TB, UK
d Department of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
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Publication History

Received 12 December 2002
Publication Date:
20 May 2003 (online)

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Abstract

N-Metallated azomethine ylides 5 were generated by the reaction of arylidene glycine imines 1 with AgOAc and triethyl­amine. These azomethine ylides undergo cycloaddition to chiral acrylamides 2 with excellent diastereoselectivity. The configuration of two of the cycloadducts (3a 1 and 3c 1 ) has been confirmed by X-ray crystallography.

Key words

cycloaddition - azomethine ylides - pyrrolidine - asymmetric

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Silver Acetate Catalysed Cycloaddition Reactions - General procedure: A mixture of imine (1.2 equiv) AgOAc (1.5 equiv), appropriate dipolarophile (1 equiv) and Et3N in dry toluene (5 mL for 1 mmol of imine) protected from the light with aluminium foil was stirred at r.t. for 12-48 h. The reaction was then quenched by addition of sat. aq NH4Cl solution and Et2O. The mixture was filtered through a pad of Celite®. The organic layer was separated, washed with H2O, brine and dried over MgSO4, filtered and the solvent evaporated. The residue was purified by flash chromatography and/or recrystallisation to afford the cycloadducts. Selected data for representative examples: ( S , S , S , R )-Ethyl-5-(2,4-dichlorophenyl)-4-[(1′-phenyl-ethyl)carbamoyl]-pyrrolidine-2-carboxylate ( 4b 2 ). White powder; mp 171-172 °C. [α] d 23 = +116 (c 1.2, CHCl3). 1H NMR (270 MHz, CDCl3): δ = 7.51 (d, 1 H, J = 7.9 Hz, Ar), 7.33-7.12 (m, 5 H, Ar), 6.93 (dd, 1 H, J = 1.8 Hz and 7.9 Hz, Ar), 6.42 (d, 1 H, J = 1.8 Hz, Ar), 4.73 (m, 1 H, CHCH3), 4.57 (d, 1 H, J = 6.0 Hz, H-5), 4.29 (q, 2 H, OCH2), 3.96 (dd, 1 H, J = 6.1 Hz and 9.5 Hz, H-2), 3.35 (ddd, 1 H, J = 3.2 Hz, 6.0 Hz and 6.7 Hz, H-4), 2.70 (br s, 1 H, NH), 2.53 (ddd, 1 H, J = 6.7 Hz, 9.5 Hz and 13.8 Hz, H2-3), 2.35 (ddd, 1 H, J = 3.2 Hz, 6.1 Hz and 13.8 Hz, H2-3), 1.29 (t, 3 H, J = 7.3 Hz, Me), 1.08 (d, 3 H, J = 8.6 Hz, Me). 13C NMR: δ = 173.4 (C=O), 170.9 (C=O), 143.0 (q), 134.5 (q), 133.8 (q), 133.3 (q), 129.1 (2 × CH), 128.6 (2 × CH), 127.6 (CH), 127.6 (CH), 126.4 (CH), 125.9 (CH), 62.6, 61.2, 58.1, 47.3, 33.6, 21.0, 14.2, IR (nujol): 3306, 1734, 1644, 1527, 1213, 1123, 1090, 1050, 1019 cm-1. MS (CI): m/z (rel. intensity, %) = 477 (4)[M+], 463 (12), 435 (base peak), 401 (15), 361 (14), 262 (17), 140 (20), 105 (34). HRMS: Calcd 434.1164 for C22H24Cl2N2O3. Found: 434.1152. ( R , R , R , R , R )-Ethyl-5-phenyl-4-{[bis(1′-phenyl-ethyl)]carbamoyl}-pyrrolidine-2-carboxylate ( 3c 1 ). Colourless needles; mp 172-173 °C. [α] d 23 = -158 (c 0.96, CHCl3). 1H NMR (270 MHz, CDCl3): δ = 7.31-7.02 (m, 11 H, Ph), 6.77-6.71 (m, 4 H, Ph), 5.31 (broad d, 1 H, J = 6.6 Hz, PhCH), 4.70 (q, 1 H, J = 7.3 Hz, PhCH), 4.23 (dq, 2 H, J = 1.9 and 7.3 Hz, OCH2), 3.95 (d, 1 H, J = 7.3 Hz, H-5), 3.87 (t, 1 H, J = 8.6 Hz, H-2), 3.43 (dd, 1 H, J = 5.3 Hz and 7.3 Hz, H-4), 2.53-2.02 (m, 2 H, H2-3), 1.46 (d, 3 H, J = 7.3 Hz, CH3), 1.42 (d, 3 H, J = 7.3 Hz, CH3), 1.29 (t, 3 H, J = 7.3 Hz, CH3). 13C NMR: δ = 173.9 (C=O), 173.1 (C=O), 141.1 (2 × Ph-1′C), 138.7 (Ph-1′C), 128.4, 128.3, 128.0, 127.8, 127.2, 126.9 (15 × CH, overlapping), 67.4, 61.0, 52.4, 52.1, 47.2, 36.9, 30.0, 19.5, 16.9, 14.3. IR (nujol): 1737, 1627, 1604, 1453, 1293, 1262, 1195, 1177, 1102, 1025, 949 cm-1. MS (CI): m/z (rel. intensity, %) = 471 (base peak) [M+], 397 (10), 367 (15), 280 (12), 246 (9), 105 (22). HRMS: Calcd 470.2569 for C30H34N2O3. Found: 470.2573. ( R , R , R , R , R )-Ethyl-5-(4-nitrophenyl)-4-[(2′,5′- trans -diphenylpyrrolidinyl)-1-carbonyl]-pyrrolidine-2-carboxylate ( 3d 3 ). White powder; mp 222-223 °C. [α] d 23 = +34 (c 0.17, CHCl3). 1H NMR (270 MHz, CDCl3):
δ = 8.09 (d, 2 H, J = 8.6 Hz, Ar), 7.44-7.31 (m, 5 H, Ar), 7.18 (d, 2 H, J = 6.6 Hz, Ar), 7.07 (t, 1 H, J = 7.3 Hz, Ar), 6.95 (t, 2 H, J = 7.3 Hz, Ar), 6.52 (d, 2 H, J = 7.3 Hz, Ar), 5.25 (d, 1 H, J = 7.3 Hz, CHPh), 5.16 (d, 1 H, J = 7.3 Hz, CHPh), 4.24 (d, 1 H, J = 7.3 Hz, H-5), 4.20 (q, 2 H, J = 7.3 Hz, OCH2), 3.69 (t, 1 H, J = 8.6 Hz, H-2), 3.25 (ddd, 1 H, J = 3.3 Hz, 4.6 Hz and 7.9 Hz, H-4), 2.51-2.19 (m, 2 H, CH2), 2.01 (ddd, 1 H, J = 4.6 Hz, 7.3 Hz and 13.2 Hz, H2-3), 1.88-1.72 (m, 2 H, CH2), 1.58 (dd, 1 H, J = 5.3 Hz and 11.9 Hz, CH2), 1.27 (t, 3 H, J = 7.3 CH3). 13C NMR: δ = 172.9 (C=O), 172.2 (C=O), 147.1 (q), 146.2 (q), 143.6 (q), 142.6 (q), 129.0 (2 × CH), 127.9 (2 × CH), 127.8 (2 × CH), 127.7 (2 × CH), 126.6 (CH), 125.4 (2 × CH), 125.1 (2 × CH), 123.6 (2 × CH), 66.1, 63.2, 62.0, 61.1, 60.2, 47.8, 36.3, 33.4, 30.0, 14.2. IR (nujol): 1736, 1611, 1511, 1416, 1353, 1309, 1272, 1187, 1171, 1063, 1028 cm-1. MS (CI): m/z (rel. intensity, %) = 514 (base peak) [M+1], 484 (12), 440 (8), 278 (10), 237 (12). HRMS: Calcd 513.2264 for C30H31N3O5. Found: 513.2239. ( R , R , R , R , S )-Ethyl-4-[(2′-hydroxy-1′-methyl-2′-phenyl-ethyl)carbamoyl]-5-(2,4-dichlorophenyl)-pyrrolidine-2-carboxylate ( 3e 1 ). White powder; mp 182-183 °C. [α] d 23 = -101 (c 1.0, CHCl3). 1H NMR (270 MHz, CDCl3):
δ = 7.40-7.15 (m, 8 H, Ar), 4.61 (d, 1 H, J = 6.6 Hz, CHOH), 4.40 (d, 1 H, J = 4.0 Hz, H-5), 4.27 (dq, 2 H, J = 1.9 and 7.3 Hz, OCH2), 4.10 (broad m, 2 H, OH + CH-CH3), 3.84 (t, 1 H, J = 7.9 Hz, H-2), 3.57 (ddd, 1 H, J = 4.0 Hz, 7.3 Hz and 10.7 Hz, H-4), 2.80 (m, 1 H, H2-3), 2.47 (s, 3 H, NMe), 2.35 (m, 1 H, H2-3), 1.33 (t, 3 H, J = 7.3 Hz, CH3), 0.72 (d, 3 H, J = 7.3 Hz, CH3). 13C NMR: δ = 173.6 (C=O), 172.8 (C=O), 141.7, 134.7, 133.7, 133.2, 129.2, 128.5, 127.9 (2 × CH), 127.3, 127.1, 126.1 (2 × CH), 76.5, 62.3, 59.8, 56.8, 43.5, 34.8, 32.5, 14.2, 11.4. IR (KBr): 3377, 2987, 1736, 1621, 1476, 1449, 1413, 1374, 1206, 1104, 1048 cm-1. MS (CI):
m/z (rel. intensity, %) = 479 (base peak) [M+], 463 (20), 314 (31), 280 (15), 176 (10), 148 (52), 135 (22), 107 (25). HRMS: Calcd 478.1426 for C24H28Cl2N2O4. Found: 478.1409.