References and Notes
Reviews:
1a
Zimmer R.
Reissig H.-U.
Modern Allene Chemistry
Vol. 2:
Krause N.
Hashmi ASK.
Wiley-VCH;
Weinheim:
2004.
p.847-876
1b
Reissig H.-U.
Hormuth S.
Schade W.
Okala Amombo MG.
Watanabe T.
Pulz R.
Hausherr A.
Zimmer R.
J. Heterocycl. Chem.
2000,
37:
597
Original publications:
1c
Okala Amombo MG.
Hausherr A.
Reissig H.-U.
Synlett
1999,
1871
1d
Flögel O.
Reissig H.-U.
Synlett
2004,
895
2a Synthesis of the γ-amino acid (-)-detoxinine: Flögel O.
Okala Amombo MG.
Reissig H.-U.
Zahn G.
Brüdgam I.
Hartl H.
Chem. Eur. J.
2003,
9:
1405
2b Synthesis of (-)-preussin: Hausherr A.
Dissertation
Freie Universität Berlin;
Berlin:
2002.
2c Synthesis of both enantiomers of anisomycin: Kaden S.
Brockmann M.
Reissig H.-U.
Helv. Chem. Acta
2005,
88:
1826
2d Synthesis of codonopsinine: Chowdhury, M. A.; Reissig, H.-U. manuscript in preparation for Synlett.
3 For a review of the Ritter reaction, see: Krimen LI.
Cota DJ.
Org. React.
1969,
17:
213
4
Typical Procedure for the Preparation of Imidazole 6a.
A solution of methoxyallene (2.80 g, 39.9 mmol) in dry THF (50 mL) under Ar was treated at -40 °C with n-BuLi (2.5 M in hexane, 14.4 mL, 35.9 mmol, deprotonation time 5-10 min). Imine 2a (5.10 g, 28.1 mmol) dissolved in dry THF (10 mL) was added within 5 min. The mixture was stirred for 2 h at -20 °C and quenched with H2O (100 mL). Warm up to r. t. was followed by extraction with Et2O (3 ¥ 100 mL), drying (Na2SO4), and concentration in vacuo, which led to crude product 3a, yield 7.00 g (99 %).
Iodine (2.54 g, 10.0 mmol) was dissolved in freshly distilled MeCN (50 mL) at 45 °C and stirred for 10 min. A solution of crude allenyl amine 3a (1.00 g, 3.98 mmol) dissolved in MeCN (10 mL) was added within 5 min and the mixture was stirred for 15 h at r. t. 10 % Na2S2O3 solution (30 mL) was added and the mixture was extracted with CH2Cl2 (3 ¥ 50 mL), dried over Na2SO4 and concentrated in vacuo furnishing crude 5a (1.95 g).
Crude 5a was dissolved in dry CH2Cl2 (4 mL) under Ar, and CF3SO3H (0.5 mL, 5.59 mmol) was added dropwise. The mixture was stirred for 1 h at r. t., treated with dilute NaHCO3 solution (30 mL), then with 10 % Na2S2O3 solution (10 mL) and extracted with CH2Cl2 (3 ¥ 50 mL). The combined organic phases were washed with H2O (1 ¥ 30 mL) and dried over Na2SO4. The crude product was purified by column chromatography (silica gel, hexane-EtOAc = 4:1) to yield 1.22 g (80 % overall yield) of 6a as yellow crystals.
Analytical Data for 4-(1-Iodoethenyl)-2-methyl-1,5-diphenylimidazole (6a).
Mp 104-105 °C. 1H NMR (500 MHz, CDCl3): δ = 2.30 (s, 3 H, Me), 5.96, 6.14 (2 d, J = 1.4 Hz, each 1 H, =CH2), 7.07-7.36 (m, 10 H, Ph) ppm. 13C NMR (126 MHz, CDCl3): δ = 14.1 (q, Me), 98.9 (s, =C-I), 127.8, 127.9, 128.3, 128.7, 129.4, 130.5 (6 d, Ph), 128.9 (t, =CH2), 129.1 (s, Ph), 129.8 (s, C-5), 136.5 (s, Ph), 138.0 (s, C-4), 144.4 (s, C-2) ppm. IR (KBr): 3185-2870 ( = CH, CH), 1600 (C = C) cm-1. MS (EI, 80 eV, 40 °C): m/z (%) = 386 (17) [M]+, 259 (100) [M - I]+, 218 (50), 184 (18), 77 (26) [C6H5]+, 43 (21), 28 (13). HRMS (EI, 80 eV, 40 °C): m/z calcd for C18H15IN2: 386.0280. Found: 386.0267.
5
Typical Procedure for the Preparation of Alkyne 7a.
To a solution of imidazole 6a (152 mg, 0.39 mmol) in dry THF (2 mL) was added at 0 °C dropwise a solution of potassium tert-butoxide (88 mg, 0.78 mmol) in THF (1 mL). The flask was flushed with Ar, sealed and allowed to stir at 0 °C for 1 h. The mixture was quenched with sat. aq NH4Cl solution (3 mL) and extracted with CH2Cl2 (3 ¥ 30 mL). The combined organic phases were dried over Na2SO4 and the crude product was purified by column chromatography (silica gel, hexane-EtOAc = 4:1), which provided 50 mg (50 %) of 7a as yellow crystals.
Analytical Data for 4-Ethynyl-2-methyl-1,5-diphenylimidazole (7a).
Mp 163-164 °C. 1H NMR (500 MHz, CDCl3): δ = 2.28 (s, 3 H, Me), 3.07 (s, 1 H, ºCH), 7.09-7.41 (m, 10 H, Ph) ppm. 13C NMR (126 MHz, CDCl3): δ = 14.2 (q, Me), 78.3 (s, ºC), 78.4 (d, H-Cº), 127.7, 127.8, 128.2, 128.9, 129.0, 129.7 (6 d, Ph), 128.8, 137.2 (2 s, Ph), 120.3 (s, C-4), 136.6 (s, C-5), 146.0 (s, C-2) ppm. IR (KBr): 3290-2850 (C-H), 2105 (CºC), 1595 (C = C) cm-1. MS (EI, 80 eV, 40 °C): m/z (%) = 258 (71) [M]+, 216 (30), 181 (5) [M - C6H5]+, 114 (23), 91 (25), 77 (55) [C6H5]+, 51 (28), 28 (100). HRMS (EI, 80 eV, 40 °C): m/z calcd for C18H14N2: 258.1157. Found: 258.1163.
6
Typical Procedure for Sonogashira Reaction 7a → 8a.
To a solution of Et3N (0.8 mL) and DMF (0.4 mL) under Ar were added iodobenzene (0.08 mL, 0.69 mmol), alkyne 7a (150 mg, 0.58 mmol), PdCl2(PPh3)2 (18 mg, 0.025 mmol), and CuI (2 mg, 0.012 mmol). The mixture was stirred at r. t. for 16 h, then quenched with sat. aq NH4Cl solution (3 mL) and extracted with CH2Cl2 (3 ¥ 30 mL). The combined organic phases were dried over Na2SO4 and the resulting crude product was purified by column chromatography (silica gel, toluene-EtOAc = 4:1) to give 150 mg (77 %) of 8a as pale yellow crystals.
Analytical Data for 4-Phenylethynyl-2-methyl-1,5-diphenylimidazole (8a).
Mp 189-190 °C. 1H NMR (500 MHz, CDCl3): δ = 2.30 (s, 3 H, Me), 7.11-7.46 (m, 15 H, Ph) ppm. 13C NMR (126 MHz, CDCl3): δ = 14.2 (q, Me), 84.3 (s, ºC), 90.4 (s, Ph-Cº), 127.7, 127.8, 127.9, 128.2, 128.3, 128.8, 128.9, 129.6, 131.4 (9 d, Ph), 121.4 (s, C-4), 123.7, 129.1, 136.8 (3 s, Ph), 136.4 (s, C-5), 146.3 (s, C-2) ppm. IR (KBr): 3055-2855 ( = CH, CH), 2570 (CºC), 1600 (C = C) cm-1. MS (EI, 80 eV, 40 °C): m/z (%) = 335 (31), 334 (100) [M]+, 333 (32), 292 (29), 291 (32), 189 (27), 167 (17), 145 (23), 139 (12), 126 (11), 125 (16), 123 (22), 105 (19), 91 (13), 57 (13). HRMS (EI, 80 eV, 40 °C): m/z calcd for C24H18N2: 334.1470. Found: 334.1464.
7a
Zhu J.
Bienaymé H.
Multicomponent Reactions
Wiley-VCH;
Weinheim:
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7b
Dömling A.
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8 For an interesting alternative approach to highly substituted imidazoles, which employs a dilithiated allene derivative and nitriles, see: Langer P.
Döring M.
Seyferth D.
Görls H.
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Rees CW.
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9b
Grimmet MR.
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Katritzky AR.
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Scriven EFV.
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Wiesman EH.
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Tsujii S.
Rinehart KL.
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9f Lee JC.
Laydon JT.
McDonnel PC.
Gallagher TF.
Kumar S.
Green D.
McNulty D.
Blumenthal MJ.
Heys JR.
Landvatter SW.
Strickler JE.
Mclaughlin MM.
Siemens IR.
Fisher SM.
Livi GP.
White JR.
Adams JL.
Young PR.
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Smietana JM.
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Gallagher TF.
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Bradbeer J.
Badger AM.
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9h
McLay IM.
Halley F.
Souness JE.
McKenna J.
Benning V.
Birrell M.
Burton B.
Belvisi M.
Collis A.
Constan A.
Foster M.
Hele D.
Jayyosi Z.
Kelley M.
Maslen C.
Miller G.
Ouldelhkim M.-L.
Page K.
Phipps S.
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Porter B.
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Redford EJ.
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2001,
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Applications in material science:
9i Synthesis of fluorescent highly substituted imidazole derivatives: Thür W.
Dissertation
LMU München:
2001.
9j
Langhals H.
Jaschke H.
Ring U.
Unold P.
Angew. Chem. Int. Ed.
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Selected new synthetic methods:
9k
Sisko J.
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9l
Fresneda PM.
Molina P.
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9n
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9o
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10 We have earlier named lithiated alkoxyallenes as ‘synthetic chameleons’ due to the many options they offer for the synthesis of heterocycles and other useful compounds: Flögel O.
Dash J.
Brüdgam I.
Hartl H.
Reissig H.-U.
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2004,
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4283 ; see also ref. 1a