α-Acidic Isocyanides in Multicomponent Chemistry

Isocyanide Chemistry: Applications in Synthesis and Material Science

Volumn , Issue , 2012, Pages 75-108

  Elders, Niels ^a   Ruijter, Eelco ^a   Nenajdenko, Valentine G ^b   Orru, Romano V A ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

^b MOSCOW STATE UNIVERSITY   (Russian Federation)

Author keywords

Atom efficiency; Diversity oriented synthesis; Heterocycles; Isocyanides; Multicomponent reactions; Step efficiency; Structural complexity; Synthesis

Indexed keywords

EID: 84885543376     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527652532.ch3     Document Type: Chapter

References (191)

1. Dömling, A. and Ugi, I. (2000) Multikomponentenreaktionen mit Isocyaniden. Angew. Chem., 112 (18), 3300-3344.
2. Dömling, A. and Ugi, I. (2000) Multicomponent reactions with isocyanides. Angew. Chem. Int. Ed., 39 (18), 3168-3210.
3. Hulme, C. and Gore, V. (2003) Multi-component reactions: emerging chemistry in drug discovery. Curr. Med. Chem., 10 (1), 51-80.
4. Orru, R.V.A. and De Greef, M. (2003) Recent advances in solution-phase multicomponent methodology for the synthesis of heterocyclic compounds. Synthesis, (10), 1471-1499.
5. Jacobi von Wangelin, A., Neumann, H., Gördes, D., Klaus, S., Strübing, D., and Beller, M. (2003) Multicomponent coupling reactions for organic synthesis: chemoselective reactions with amide-aldehyde mixtures. Chem. Eur. J., 9 (18), 4286-4294.
6. Nair, V., Rajesh, C., Vinod, A.U., Bindu, S., Sreekanth, A.R., Mathen, J.S., and Balagopal, L. (2003) Strategies for heterocyclic construction via novel multicomponent reactions based on isocyanides and nucleophilic carbenes. Acc. Chem. Res., 36 (12), 899-907.
7. Zhu, J. (2003) Recent developments in the isonitrile-based multicomponent synthesis of heterocycles. Eur. J. Org. Chem., (7), 1133-1144.
8. Balme, G., Bossharth, E., and Monteiro, N. (2003) Pd-assisted multicomponent synthesis of heterocycles. Eur. J. Org. Chem., (21), 4101-4111.
9. Simon, C., Constantieux, T., and Rodriguez, J. (2004) Utilisation of 1,3-dicarbonyl derivatives in multicomponent reactions. Eur. J. Org. Chem., (24), 4957-4980.
10. Ramón, D.J. and Yus, M. (2005) Neue Entwicklungen in der asymmetrischen mehrkomponenten -reaktion. Angew. Chem., 117 (11), 1628-1661.
11. Ramón, D.J. and Yus, M. (2005) Asymmetric multicomponent reactions (AMCRs): the new frontier. Angew. Chem. Int. Ed., 44 (11), 1602-1634.
12. Tempest, P. (2005) Recent advances in heterocycle generation using the efficient Ugi multiple-component condensation reaction. Curr. Opin. Drug. Discov. Dev., 8 (6), 776-788.
13. Dömling, A. (2006) Recent developments in isocyanide based multicomponent reactions in applied chemistry. C hem. Rev., 106 (1), 17-89.
14. Godineau, E. and Landais, Y. (2009) Radical and radical-ionic multicomponent processes. Chem. Eur. J., 15 (13), 3044-3055.
15. Strecker, A. (1850) Ueber die künstliche Bildung der Milchsäure und einen neuen, dem Glycocoll homologen Körper. Liebigs Ann. Chem., 75 (1), 27-45.
16. Strecker, A. (1854) Ueber einen neuen aus Aldehyd-Ammoniak und Blausäure entstehenden Körper. Ann. Chem. Pharm., 91 (3), 349-351.
17. Hantzsch, A. (1882) Condensationprodukte aus Aldehydammoniak und Ketoniartigen Verbindungen. Chem. Ber., 14 (2), 1637-1638.
18. Biginelli, P. (1891) Ueber Aldehyduramide des Acetessigäthers. Ber. Dtsch Chem. Ges., 24 (1), 1317-1319.
19. Biginelli, P. (1891) Ueber Aldehyduramide des Acetessigäthers. II. Ber. Dtsch Chem. Ges., 24 (2), 2962-2967.
20. Mannich, C. and Krosche, W. (1912) Ueber ein Kondensationsprodukt aus Formaldehyd, Ammoniak und Antipyrin. Arch. Pharm., 250 (1), 647-667.
21. Passerini, M. and Simone, L. (1922) Gazz. Chim. Ital., 52, 126-129.
22. Passerini, M. and Simone, L. (1922) Gazz. Chim. Ital., 52, 181-189.
23. Ugi, I. and Meyr, R. (1958) Neue Darstellungsmethode für Isonitrile. Angew. Chem., 70 (23), 702-703.
24. Ugi, I., Meyr, R., and Steinbrückner, C. (1959) Versuche mit Isonitrilen. Angew. Chem., 71 (11), 386.
25. Lieke, W. (1859)über das Cyanallyl. Liebigs Ann. Chem., 112 (3), 316-321.
26. Ugi, I., Betz, W. (1960) DE1177146.
27. Chem. Abstr., 61, 14536e.
28. Beecham Group Ltd (1974) FR2260577.
29. Chem. Abstr., 83, 206251.
30. van Leusen, A.M., Strating, J. (1970) Q. Rep. Sulfur Chem., 5, 67.
31. van Leusen, A.M., Boerma, G.J.M., Helmholdt, R.B., Siderius, H., and Strating, J. (1972) Chemistry of sulfonylmethylisocyanides. Simple synthetic approaches to a new versatile chemical building block. Tetrahedron Lett., 13 (23), 2367-2378.
32. Schöllkopf, U., Hoppe, D., and Jentsch, R. (1975) Synthesen mit α-metallierten Isocyaniden, XXIX. Höhere Aminosäuren durch Alkylieren von α-metallierten α-Isocyan-propionsäure -und-essigsäureestern. Chem. Ber., 108 (6), 1580-1592.
33. Matsumoto, K., Suzuki, M., Yoneda, N., and Miyoshi, M. (1977) Alkylation of α-isocyanoacetamides; Synthesis of 1,4,4-trisubstituted 5-oxo-4,5 -dihydroimidazoles. Synthesis, (4), 249-250.
34. van Leusen, A.M., Bourma, R.J., and Possel, O. (1975) Phase-transfer mono -alkylation of tosylmethylisocyanide. Tetrahedron Lett., 16 (40), 3487-3488.
35. Murakami, M., Hasegawa, N., Tomita, I., Inouye, M., and Ito, Y. (1989) Fluoride catalyzed Michael reaction of α-isocyanoesters with α, β-unsaturated carbonyl compounds. Tetrahedron Lett., 30 (10), 1257-1260.
36. Housseman, C. and Zhu, J. (2006) Mono alkylation of α-Isocyano acetamide to its higher homologues. Synlett, (11), 1777-1779.
37. Schöllkopf, U., Hoppe, D., and Jentsch, R. (1971) Höhere Aminosäuren durch Alkylieren von α-metallierten Isocyan-essig-oder-propionsäureestern. Angew. Chem., 83 (5), 357-358.
38. Schöllkopf, U., Hoppe, D., and Jentsch, R. (1971) Higher amino acids by alkylation of α-metalated isocyano -acetic or-propionic esters. Angew. Chem. Int. Ed., 10 (5), 331-333.
39. Ito, Y., Higuchi, N., and Murakami, M. (1988) Claisen rearrangement of allylic α-isocyano-esters-regioselective allylation of α-isocyanoesters at the α-carbon. Tetrahedron Lett., 29 (40), 5151-5154.
40. Ito, Y., Sawamura, M., Matsuoka, M., Matsumoto, Y., and Hayashi, T. (1987) Palladium-catalyzed allylation of α-isocyanocarboxylates. Tetrahedron Lett., 28 (41), 4849-4852.
41. Bonne, D., Dekhane, M., and Zhu, J. (2007) Modulating the reactivity of α-isocyanoacetates: multicomponent synthesis of 5-methoxyoxazoles and furopyrrolones. Angew. Chem., 119 (14), 2537-2540.
42. Bonne, D., Dekhane, M., and Zhu, J. (2007) Modulating the reactivity of α-isocyanoacetates: multicomponent synthesis of 5-methoxyoxazoles and furopyrrolones. Angew. Chem. Int. Ed., 46 (14), 2485-2488.
43. Matsumoto, K., Suzuki, M., and Miyoshi, M. (1973) Synthesis of amino acids and related compounds. 4. New synthesis of α-amino acids. J. Org. Chem., 38 (11), 2094-2096.
44. Olijnsma, T., Engberts, J.B.F.N., and Strating, J. (1972) Rec. Trav. Chim. Pays-Bas, 91, 209.
45. Hundscheid, F.J.A., Tandon, V.K., Rouwette, P.H.F.M., and van Leusen, A.M. (1987) Synthesis of chiral sulfonylmethyl isocyanides, and comparison of their propensities in asymmetric induction reactions with acetophenones. Tetrahedron, 43 (21), 5073-5088.
46. Barrett, A.G.M., Cramp, S.M., Hennessy, A.J., Procopiou, P.A., and Roberts, R.S. (2001) Oxazole synthesis with minimal purification: synthesis and application of a ROMPgel tosmic reagent. Org. Lett., 3 (2), 271-274.
47. Sisko, J., Mellinger, M., Sheldrake, P.W., and Baine, N.H. (1996) An efficient method for the synthesis of substituted TosMIC precursors. Tetrahedron Lett., 37 (45), 8113-8116.
48. Wright, J.J.K., Cooper, A.B., McPhail, A.T., Merrill, Y., Nagabhushan, T.L., and Puar, M.S. (1982) X-Ray crystal structure determination and synthesis of the new isonitrile-containing antibiotics, hazimycin factors 5 and 6. J. Chem. Soc. Chem. Commun., (20), 1188-1190.
49. Urban, R., Marquarding, D., Seidel, P., Ugi, I., and Weinelt, A. (1977) Notiz zur Synthese optisch aktiver α -Isocyancarbonsäure-Derivate für Peptidsynthesen mittels Vier -Komponenten-Kondensation (4 CC). Chem. Ber., 110 (5), 2012-2015.
50. Waki, M. and Meienhofer, J. (1977) Efficient preparation of N α-formylamino acid tert-butyl esters. J. Org. Chem., 42 (11), 2019-2020.
51. Kamer, P.C.J., Cleij, M.C., Nolte, R.J.M., Harada, T., Hezemans, A.M.F., and Drenth, W. (1988) Atropisomerism in polymers. Screw-sense selective polymerization of isocyanides by inhibiting the growth of one enantiomer of a racemic pair of helices. J. Am. Chem. Soc., 110 (5), 1581-1587.
52. Seebach, D., Adam, G., Gees, T., Schiess, M., and Weigand, W. (1988) Scope and limitations of the TiCl 4 -mediated additions of isocyanides to aldehydes and ketones with formation of α-hydroxycarboxylic acid amides. Chem. Ber., 121 (3), 507-518.
53. Bowers, M.M., Carroll, P., and Joullié, M.M. (1989) Model studies directed toward the total synthesis of 14-membered cyclopeptide alkaloids: synthesis of prolyl peptides via a four-component condensation. J. Chem. Soc., Perkin Trans. 1, (5), 857-865.
54. Owens, T.D., Araldi, G.-L., Nutt, R.F., and Semple, J.E. (2001) Concise total synthesis of the prolyl endopeptidase inhibitor eurystatin A via a novel Passerini reaction-deprotection-acyl migration strategy. Tetrahedron Lett., 42 (36), 6271-6274.
55. Wehner, V., Stilz, H.-U., Osipov, S.N., Golubev, A.S., Sieler, J., and Burger, K. (2004) Trifluoromethyl-substituted hydantoins, versatile building blocks for rational drug design. Tetrahedron, 60 (19), 4295-4302.
56. Horwell, D.C., Nichols, P.D., and Roberts, E. (1994) Conformationally constrained amino acids: synthesis of novel 3,4-cyclised tryptophans. Tetrahedron Lett., 35 (6), 939-940.
57. Obrecht, R., Herrmann, R., and Ugi, I. (1985)) Isocyanide synthesis with phosphoryl chloride and diisopropylamine. S ynthesis, (4), 400-402.
58. Zhu, J., Wu, X., and Danishefsky, S.J. (2009) On the preparation of enantiomerically pure isonitriles from amino acid esters and peptides. Tetrahedron Lett., 50 (5), 577-579.
59. Pifferi, G., LiBassi, G., and Broccali, G. (1976) Semisynthetic β-lactam antibiotics. I. α-Isocyanobenzyl -penicillins and cephalosporins. Heterocycles, 4 (4), 759-765.
60. Skorna, G. and Ugi, I. (1977) Isocyanid-Synthese mit Diphosgen. Angew. Chem., 89 (4), 267-268.
61. Skorna, G. and Ugi, I. (1977) Isocyanide synthesis with diphosgene. Angew. Chem. Int. Ed. Engl., 16 (4), 259-260.
62. van der Eijk, J.M., Nolte, R.J.M., Richters, V.E.M., and Drenth, W. (1981) J. R. Neth. Chem. Soc., 100, 222-226.
63. Nishimura, S., Yasuda, N., Sasaki, H., Matsumoto, Y., Kanimura, T., Sakane, K., and Takaya, T. (1990) Synthesis and β-lactamase inhibitory activity of 3-cyano-3-cephem derivatives. Bull. Chem. Soc. Jpn, 63 (2), 412-416.
64. Ikota, N. (1990) Synthetic studies on optically active β-lactams. II. Asymmetric synthesis of β-lactams by [2 + 2]cyclocondensation using heterocyclic compounds derived from L-(+)-tartaric acid, (S)-or (R)-glutamic acid, and (S)-serine as chiral auxiliaries. Chem. Pharm. Bull., 38 (6), 1601-1608.
65. Creedon, S.M., Crowley, H.K., and McCarthy, D.G. (1998) Dehydration of formamides using the Burgess reagent: a new route to isocyanides. J. Chem. Soc., Perkin Trans. 1, (6), 1015-1018.
66. Banfi, L., Guanti, G., Riva, R., Basso, A., and Calcagno, E. (2002) Short synthesis of protease inhibitors via modified Passerini condensation of N-Boc-α -aminoaldehydes. Tetrahedron Lett., 43 (22), 4067-4070.
67. de Witte, P.A.J., Castriciano, M., Cornelissen, J.J.L.M., Scolaro, L.M., Nolte, R.J.M., and Rowan, A.E. (2003) Helical polymer-anchored porphyrin nanorods. Chem. Eur. J., 9 (8), 1775-1781.
68. Zhao, G., Bughin, C., Bienaymé, H., and Zhu, J. (2003) Synthesis of isocyano peptides by dehydration of the N-formyl derivatives. Synlett, (8), 1153-1154.
69. Vriezema, D.M., Kros, A., de Gelder, R., Cornelissen, J.J.L.M., Rowan, A.E., and Nolte, R.J.M. (2004) Electroformed giant vesicles from thiophene-containing rod-coil diblock copolymers. Macromolecules, 37 (12), 4736-4739.
70. Bughin, C., Zhao, G., Bienaymé, H., and Zhu, J. (2006) 5-aminooxazole as an internal traceless activator of C-terminal carboxylic acid: rapid access to diversely functionalized cyclodepsipeptides. Chem. Eur. J., 12 (4), 1174-1184.
71. Metselaar, G.A., Adams, P.J.H.M., Nolte, R.J.M., Cornelissen, J.J.L.M., and Rowan, A.E. (2007) Polyisocyanides derived from tripeptides of alanine. Chem. Eur. J., 13 (3), 950-960.
72. Schwartz, E., Kitto, H.J., de Gelder, R., Nolte, R.J.M., Rowan, A.E., and Cornelissen, J.J.L.M. (2007) Synthesis, characterisation and chiroptical properties of " click " able polyisocyanopeptides. J. Mater. Chem., 17 (19), 1876-1884.
73. Nunami, K.-I., Suzuki, M., Hayashi, K., Matsumoto, K., Yoneda, N., and Takiguchi, K. (1985) Synthesis and herbicidal activities of α-isocyanocycloal kylideneacetamides. Agric. Biol. Chem., 49 (10), 3023-3028.
74. Nunami, K.-I., Suzuki, M., Matsumoto, K., Yoneda, N., and Takiguchi, K. (1984) Syntheses and biological activities of isonitrile dipeptides. Agric. Biol. Chem., 48 (4), 1073-1076.
75. Takiguchi, K., Yamada, K., Suzuki, M., Nunami, K.-I., Hayashi, K., and Matsumoto, K. (1989) Antifungal activities of α-isocyano-β -phenylpropionamides. Agric. Biol. Chem., 53 (1), 77-82.
76. Soloshonok, V.A. and Hayashi, T. (1994) Gold(I)-catalyzed asymmetric aldol reactions of fluorinated benzaldehydes with an α-isocyanoacetamide. Tetrahedron: Asymmetry, 5 (6), 1091-1094.
77. Beck, B., Larbig, G., Mejat, B., Magnin -Lachaux, M., Picard, A., Herdtweck, E., and Dömling, A. (2003) Short and diverse route toward complex natural product-like macrocycles. O rg. Lett., 5 (7), 1047-1050.
78. van Leusen, D., van Leusen, A.M. (2001) Synthetic uses of tosylmethyl isocyanide (TosMIC). Org. React., 57 (3), 417-679.
79. Schöllkopf, U. (1977) Neuere Anwendungen α-metallierter Isocyanide in der organischen Synthese. Angew. Chem., 89 (6), 351-360.
80. Schöllkopf, U. (1977) Recent applications of α -metalated isocyanides in organic synthesis. Angew. Chem. Int. Ed., 16 (6), 339-348.
81. Seagusa, T., Ito, Y., Kinoshita, H., and Tomita, S. (1971) Synthetic reactions by complex catalysts. XIX. Copper-catalyzed cycloaddition reactions of isocyanides. Novel synthesis of Δ 1-pyrroline and Δ 2-oxazoline. J. Org. Chem., 36 (22), 3316-3323.
82. Hoppe, D. and Schöllkopf, U. (1972) Synthesen mit α-metallierten Isocyaniden, XV: 4 -äthoxycarbonyl-2 -oxazoline und ihre Hydrolyse zu N-Formyl-β-hydroxy-α -aminosäureäthylestern. Liebigs Ann. Chem., 763 (1), 1-16.
83. Meyer, R., Schöllkopf, U., and Böhme, P. (1977) Synthesen mit α-metallierten Isocyaniden, XXXIX. 2-Imidazoline aus α-metallierten Isocyaniden und Schiff-Basen; 1,2-Diamine und 2,3-Diaminoalkansäuren. Liebigs Ann. Chem., (7), 1183-1193.
84. Hayashi, T., Kishi, E., Soloshonok, V.A., and Uozumi, Y. (1996) Erythro-selective aldol-type reaction of N -sulfonylaldimines with methyl isocyanoacetate catalyzed by gold(I). Tetrahedron Lett., 37 (28), 4969-4972.
85. Lin, Y.-R., Zhou, X.-T., Dai, L.-X., and Sun, J. (1997) Ruthenium complex -catalyzed reaction of isocyanoacetate and N-sulfonylimines: stereoselective synthesis of N-sulfonyl-2-imidazolines. J. Org. Chem., 62 (6), 1799-1803.
86. Benito-Garagorri, D., Bocokíc, V., and Kirchner, K. (2006) Copper(I)-catalyzed diastereoselective formation of oxazolines and N-sulfonyl-2 -imidazolines. Tetrahedron Lett., 47 (49), 8641-8644.
87. Meyer, R., Schöllkopf, U., Madawinata, K., and Stafforst, D. (1978) Totalsynthese von (±)-2,2-Diethyl-3-methyl-und (±)-2,2-Diethyl-3,6-dimethyl-6 -(phenoxyacetamido)penam-3 -carbonsäure. Liebigs Ann. Chem., (12), 1982-1989.
88. Suzuki, M., Iwasaki, T., Matsumoto, K., and Okumura, K. (1972) Convenient syntheses of aroylamino acids and α-amino ketones. Communication, 2 (4), 237.
89. Suzuki, M., Iwasaki, T., Miyoshi, M., Okumura, K., and Matsumoto, K. (1973) Synthesis of amino acids and related compounds. 6. New convenient synthesis of α-C-acylamino acids and α-amino ketones. J. Org. Chem., 38 (20), 3571-3575.
90. Matsumoto, K., Suzuki, M., Yoneda, N., and Miyoshi, M. (1976) A new, convenient synthesis of 3-amino-4 -hydroxy-2-oxo-1,2-dihydroquinoline derivatives via 5-(2-acylaminophenyl)-4 -methoxycarbonyl-1,3-oxazoles. Synthesis, (12), 805-807.
91. Nunami, K.-I., Suzuki, M., Matsumoto, K., Miyoshi, M., and Yoneda, N. (1979) Reaction of phthalic anhydrides with methyl isocyanoacetate: a useful synthesis of 1,2-dihydro-1 -oxoisoquinolines. Chem. Pharm. Bull., 27 (6), 1373-1377.
92. Henneke, K.-W., Schöllkopf, U., and Neudecker, T. (1979) Synthesen mit α-metallierten Isocyaniden, XLII. Bi -, Ter-und Quateroxazole aus α -anionisierten Isocyaniden und Acylierungsmitteln; α-Aminoketone und α, α-Diaminoketone. Liebigs Ann. Chem., (9), 1370-1387.
93. Gerecke, M., Kyburz, E., Borer, R., and Gassner, W. (1994) New tetracyclic derivatives of imidazo[1,5-a][1,4] benzodiazepines and of imidazo[1,5-a] -thieno[3,2-f][1,4]-diazepines. Heterocycles, 39 (2), 693-722.
94. Matecka, D., Wong, G., Gu, Z.-Q., Skolnick, P., and Rice, K.C. (1995) Med. Chem. Res., 5 (1), 63-76.
95. Jacobsen, E.J., Stelzer, L.S., TenBrink, R.E., Belonga, K.L., Carter, D.B., Im, H.K., Bin Im, W., Sethy, V.H., Tang, A.H., VonVoigtlander, P.F., Petke, J.D., Zhong, W.-Z., and Mickelson, J.W. (1999) Piperazine imidazo[1,5-a] quinoxaline ureas as high-affinity GABA A ligands of dual functionality. J. Med. Chem., 42 (7), 1123-1144.
96. Grigg, R., Lansdell, M.I., and Thornton -Pett, M. (1999) Silver acetate catalysed cycloadditions of isocyanoacetates. Tetrahedron, 55 (7), 2025-2044.
97. Kanazawa, C., Kamijo, S., and Yamamoto, Y. (2006) Synthesis of imidazoles through the copper-catalyzed cross-cycloaddition between two different isocyanides. J. Am. Chem. Soc., 128 (33), 10662-10663.
98. Bonin, M.-A., Giguere, D., and Roy, R. (2007) N-Arylimidazole synthesis by cross-cycloaddition of isocyanides using a novel catalytic system. Tetrahedron, 63 (23), 4912-4917.
99. Suzuki, M., Moriya, T., Matsumoto, K., and Miyoshi, M. (1982) A new convenient synthesis of 5-amino-1,3 -thiazole-4-carboxylic acids. Synthesis, (10), 874-875.
100. Solomon, D.M., Rizvi, R.K., and Kaminski, J.J. (1987) Observations on the reactions of isocyanoacetane esters with isothiocyanates and isocyanates. Heterocycles, 26 (3), 651-674.
101. Boros, E.E., Johns, B.A., Garvey, E.P., Koble, C.S., and Miller, W.H. (2006) Synthesis and HIV-integrase strand transfer inhibition activity of 7-hydroxy[1,3]thiazolo[5,4-b]pyridin -5(4H)-ones. Bioorg. Med. Chem. Lett., 16 (21), 5668-5672.
102. Suzuki, M., Miyoshi, M., and Matsumoto, K. (1974) Synthesis of amino acids and related compounds. 7. Convenient synthesis of 3-substituted pyrrole-2,4-dicarboxylic acid esters. J. Org. Chem., 39 (13), 1980.
103. Matsumoto, K., Suzuki, M., Ozaki, Y., and Miyoshi, M. (1976) The synthesis of 3-substituted pyrrole-2,4-dicarboxylic acid esters: reaction of methyl isocyanoacetate with aldehydes. Agric. Biol. Chem., 40 (11), 2271-2274.
104. Sakai, K., Suzuki, M., Nunami, K.-I., Yoneda, N., Onoda, Y., and Iwasawa, Y. (1980) Syntheses of 3-substituted pyrrole derivatives with antiinflammatory activity. Chem. Pharm. Bull., 28 (8), 2384-2393.
105. Barton, D.H.R. and Zard, S.Z. (1985) A new synthesis of pyrroles from nitroalkenes. J. Chem. Soc. Chem. Commun., 1098-1100.
106. Ono, N., Kawamura, H., and Maruyama, K. (1989) A convenient synthesis of trifluoromethylated pyrroles and porphyrins. Bull. Chem. Soc. Jpn, 62 (10), 3386-3388.
107. Barton, D.H.R., Kervagoret, J., and Zard, S.Z. (1990) A useful synthesis of pyrroles from nitroolefins. Tetrahedron, 46 (21), 7587-7598.
108. Lash, T.D., Bellettini, J.R., Bastian, J.A., and Couch, K.B. (1994) Synthesis of pyrroles from benzyl isocyanoacetate. Synthesis, (2), 170-172.
109. Ono, N., Katayama, H., Nisyiyama, S., and Ogawa, T. (1994) Regioselective synthesis of 5-unsubstituted benzyl pyrrole-2-carboxylates from benzyl isocyanoacetate. J. Heterocycl. Chem., 31 (4), 707-710.
110. Uno, H., Sakamoto, K., Tominaga, T., and Ono, N. (1994) A new approach to β-fluoropyrroles based on the Michael addition of isocyanomethylide anions to α-fluoroalkenyl sulfones and sulfoxides. Bull. Chem. Soc. Jpn, 67 (5), 1441-1448.
111. Vicente, M.G.H., Tome, A.C., Walter, A., and Cavaleiro, J.A.S. (1997) Synthesis and cycloaddition reactions of pyrrole -fused 3-sulfolenes: a new versatile route to tetrabenzoporphyrins. Tetrahedron Lett., 38 (20), 3639-3642.
112. Schmidt, W. and Monforts, F.-P. (1997) Synthesis of a novel enantiomerically pure chlorin as a potential subunit for an artificial photosynthetic reaction center. Synlett, (8), 903-904.
113. Abel, Y., Haake, E., Haake, G., Schmidt, W., Struve, D., Walter, A., and Monforts, F. (1998) Eine einfache und flexible Synthese von Pyrrolen aus α, β -ungesättigten Sulfonen. Helv. Chim. Acta, 81 (11), 1978-1996.
114. Bullington, J.L., Wolff, R.R., and Jackson, P.F. (2002) Regioselective preparation of 2-substituted 3,4-diaryl pyrroles: a concise total synthesis of Ningalin B. J. Org. Chem., 67 (26), 9439-9442.
115. Kamijo, S., Kanazawa, C., and Yamamoto, Y. (2005) Phosphine -catalyzed regioselective heteroaromatization between activated alkynes and isocyanides leading to pyrroles. T etrahedron Lett., 46 (15), 2563-2566.
116. Kamijo, S., Kanazawa, C., and Yamamoto, Y. (2005) Copper-or phosphine-catalyzed reaction of alkynes with isocyanides. Regioselective synthesis of substituted pyrroles controlled by the catalyst. J. Am. Chem. Soc., 127 (25), 9260-9266.
117. Larionov, O.V. and de Meijere, A. (2005) Vielseitige direkte Synthese von oligosubstituierten Pyrrolen durch Cycloaddition von α-metallierten Isocyaniden an Acetylene. Angew. Chem., 117 (35), 5809-5813.
118. Larionov, O.V. and de Meijere, A. (2005) Versatile direct synthesis of oligosubstituted pyrroles by cycloaddition of α-metalated isocyanides to acetylenes. Angew. Chem. Int. Ed., 44 (35), 5664-5667.
119. Guo, C., Xue, M.-X., Zhu, M.-K., and Gong, L.-Z. (2008) Organocatalytic asymmetric formal [3 + 2] cycloaddition reaction of isocyanoesters to nitroolefins leading to highly optically active dihydropyrroles. Angew. Chem., 120 (18), 3462-3465.
120. Guo, C., Xue, M.-X., Zhu, M.-K., and Gong, L.-Z. (2008) Organocatalytic asymmetric formal [3 + 2] cycloaddition reaction of isocyanoesters to nitroolefins leading to highly optically active dihydropyrroles. Angew. Chem. Int. Ed., 47 (18), 3414-3417.
121. Tsunenishi, Y., Ishida, H., Itoh, K., and Ohno, M. (2000) Heterocyclization of [60]fullerene with isocyanides. Synlett, (9), 1318-1320.
122. Schöllkopf, U. and Porsch, P.-H. (1973) Synthesen mit α-metallierten Isocyaniden, XXV. 4-Cyan-2 -isocyanalkansäure -äthylester, 4-Cyan-2 -(formylamino)alkansäure -äthylester und 4-Cyan-5(4)-pyrrolin-2-carbonsäure -ä thylester aus α-metallierten Isocyanalkansäure -äthylestern und Acrylnitrilen. Chem. Ber., 106 (10), 3382-3390.
123. Schöllkopf, U. and Hantke, K. (1973) Synthesen mit α-metallierten Isocyaniden, XXIV. α -Isocyanglutarsäure-diäthylester, Glutaminsäure-Derivate und Pyrrolincarbonsäure -äthylester aus α-metalliertem Isocyanessigsäure-oder-propionsäure -äthylester und Acrylsäureestern. Liebigs Ann. Chem., (9), 1571-1582.
124. Possel, O. and van Leusen, A.M. (1977) Synthesis of oxazoles, imidazoles and pyrroles with the use of mono -substituted tosylmethyl isocyanides. Heterocycles, 7 (1), 77-80.
125. Horne, D.A., Yakushijin, K., and Buechi, G. (1994) A two-step synthesis of imidazoles from aldehydes via 4-tosyloxazolines. Heterocycles, 39 (1), 139-154.
126. Hundscheid, F.J.A., Tandon, V.K., Rouwette, P.H.F.M., and van Leusen, A.M. (1987) Rec. Trav. Chim. Pays-Bas, 106, 159-160.
127. Atkins, J.M. and Vedejs, E. (2005) A two-stage iterative process for the synthesis of poly-oxazoles. Org. Lett., 7 (15), 3351-3354.
128. van Leusen, A.M., Wildeman, J., and Oldenziel, O.T. (1977) Chemistry of sulfonylmethyl isocyanides. 12. Base-induced cycloaddition of sulfonylmethyl isocyanides to C,N double bonds. Synthesis of 1,5-disubstituted and 1,4,5-trisubstituted imidazoles from aldimines and imidoyl chlorides. J. Org. Chem., 42 (7), 1153-1159.
129. van Leusen, A.M., Siderius, H., Hoogenboom, B.E., and van Leusen, D. (1972) A new and simple synthesis of the pyrrole ring system from Michael acceptors and tosylmethylisocyanides. Tetrahedron Lett., 13 (52), 5337-5340.
130. ten Have, R., Leusink, F.R., and van Leusen, A.M. (1996) An efficient synthesis of substituted 3(4) -nitropyrroles from nitroalkenes and tosylmethyl isocyanides. Synthesis, (7), 871-876.
131. Beaza, A., Mendiola, J., Burgos, C., Alvarez-Builla, J., and Vaquero, J.J. (2005) Heterocyclizations with tosylmethyl isocyanide derivatives. A new approach to substituted azolopyrimidines. J. Org. Chem., 70 (12), 4879-4882.
132. Hoppe, I. and Schöllkopf, U. (1976) Cycloaddition von " Isocyanketen " an Benzophenonanil und Thioimidsäureester zu β-Lactamen. Chem. Ber., 109 (2), 482-487.
133. Ito, Y., Sawamura, M., Hamashima, H., Emura, T., and Hayashi, T. (1989) Asymmetric aldol reaction of α -ketoesters with isocyanoacetate and isocyanoacetamide catalyzed by a chiral ferrocenylphosphine-gold(I) complex. Tetrahedron Lett., 30 (35), 4681-4684.
134. Ozaki, Y., Maeda, S., Iwasaki, T., Matsumoto, K., Odawara, A., Sasaki, Y., and Morita, T. (1983) Syntheses of 5-substituted oxazole-4-carboxylic acid derivatives with inhibitory activity on blood platelet aggregation. Chem. Pharm. Bull., 31 (12), 4417-4424.
135. Coffin, A.R., Roussell, M.A., Tserlin, E., and Pelkey, E.T. (2006) Regiocontrolled synthesis of pyrrole-2 -carboxaldehydes and 3-pyrrolin-2-ones from pyrrole Weinreb amides. J. Org. Chem., 71 (17), 6678-6681.
136. Chupp, J.P. and Leschinsky, K.L. (1980) Heterocycles from substituted amides. VII. Oxazoles from 2-isocyanoacetamides. J. Heterocycl. Chem., 17 (4), 705-709.
137. Chupp, J.P. and Leschinsky, K.L. (1980) Heterocycles from substituted amides. VIII. Oxazole derivatives from reaction of isocyanates with 2-isocyanoacetamides. J. Heterocycl. Chem., 17 (4), 711-715.
138. Schöllkopf, U., Hausberg, H.-H., Hoppe, I., Segal, M., and Reiter, U. (1978) Asymmetrische Synthese von α-Alkyl-α-aminocarbonsäuren durch Alkylierung von 1-chiral-substituierten 2-Imidazolin-5-onen. Angew. Chem., 90 (2), 136-138.
139. Schöllkopf, U., Hausberg, H.-H., Hoppe, I., Segal, M., and Reiter, U. (1978) Asymmetric synthesis of α-alkyl-α-aminocarboxylic acids by alkylation of 1-chiral-substituted 2-imidazolin-5-ones. Angew. Chem. Int. Ed., 17 (2), 117-119.
140. Schöllkopf, U., Hausberg, H.-H., Segal, M., Reiter, U., Hoppe, I., Saenger, W., and Lindner, K. (1981) Asymmetrische Synthesenüber heterocyclische Zwischenstufen, IV. Asymmetrische Synthese von α-Methylphenylalanin und seinen Analoga durch Alkylieren von 1-chiral substituiertem 4-Methyl-2 -imidazolin-5-on. Liebigs Ann. Chem., (3), 439-458.
141. Sisko, J. (1998) A one-pot synthesis of 1-(2,2,6,6-tetramethyl-4-piperidinyl)-4 -(4-fluorophenyl)-5-(2-amino-4 -pyrimidinyl)-imidazole: a potent inhibitor of P38 MAP kinase. J. Org. Chem., 63 (13), 4529-4531.
142. Gracias, V., Gasiecki, A.F., and Djuric, S.W. (2005) Synthesis of fused bicyclic imidazoles by sequential van Leusen/ring-closing metathesis reactions. Org. Lett., 7 (15), 3183-3186.
143. Lee, J.C., Laydon, J.T., McDonnell, P.C., Gallagher, T.F., Kumar, S., Green, D., McNulty, D., Blumenthal, M.J., Keys, J.R., Landvatter, S.W., Strickler, J.E., McLaughlin, M.M., Siemens, I.R., Fisher, S.M., Livi, G.P., White, J.R., Adams, J.L., and Young, P.R. (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature, 372 (6508), 739-746.
144. Antuch, W., Menon, S., Chen, Q.-Z., Lu, Y., Sakamuri, S., Beck, B., Schauer -Vukašinović, V., Agarwal, S., Hess, S., and Dömling, A. (2006) Design and modular parallel synthesis of a MCR derived α-helix mimetic protein-protein interaction inhibitor scaffold. Bioorg. Med. Chem. Lett., 16 (6), 1740-1743.
145. Neochoritis, C., Stephanidou -Stephanatou, J., and Tsoleridis, C.A. (2009) Heterocyclizations via TosMIC -based multicomponent reactions: a new approach to one-pot facile synthesis of substituted quinoxaline derivatives. Synlett, (2), 302-305.
146. Wu, B., Wen, J., Zhang, J., Li, J., Xiang, Y.-Z., and Yu, X.-Q. (2009) One-pot van Leusen synthesis of 4,5-disubstituted oxazoles in ionic liquids. Synlett, (3), 500-504.
147. Baxendale, I.R., Buckle, C.D., Ley, S.V., and Tamborini, L. (2009) A base -catalysed one-pot three-component coupling reaction leading to nitrosubstituted pyrroles. Synthesis, (9), 1485-1493.
148. Sun, X., Janvier, P., Zhao, G., Bienaymé, H., and Zhu, J. (2001) A novel multicomponent synthesis of polysubstituted 5-aminooxazole and its new scaffold-generating reaction to pyrrolo[3,4-b]pyridine. Org. Lett., 3 (6), 877-880.
149. Lobrégat, V., Alcaraz, G., Bienaymé, H., and Vaultier, M. (2001) Application of the " resin-capture-release " methodology to macrocyclisation via intramolecular Suzuki-Miyaura coupling. Chem. Commun., (9), 817-818.
150. Janvier, P., Sun, X., Bienaymé, H., and Zhu, J. (2002) Ammonium chloride -promoted four-component synthesis of pyrrolo[3,4-b]pyridin-5-one. J. Am. Chem. Soc., 124 (11), 2560-2567.
151. Fayol, A. and Zhu, J. (2002) Synthesis of furoquinolines by a multicomponent domino process. Angew. Chem., 114 (19), 3785-3787.
152. Fayol, A. and Zhu, J. (2002) Synthesis of furoquinolines by a multicomponent domino process. Angew. Chem. Int. Ed., 41 (19), 3633-3635.
153. Janvier, P., Bienaymé, H., and Zhu, J. (2002) A five-component synthesis of hexasubstituted benzene. Angew. Chem., 114 (22), 4467-4470.
154. Janvier, P., Bienaymé, H., and Zhu, J. (2002) A five-component synthesis of hexasubstituted benzene. Angew. Chem. Int. Ed., 41 (22), 4291-4294.
155. Wang, Q., Xia, Q., and Ganem, B. (2003) A general synthesis of 2-substituted-5-aminooxazoles: building blocks for multifunctional heterocycles. Tetrahedron Lett., 44 (36), 6825-6827.
156. Wang, Q. and Ganem, B. (2003) New four-component condensations leading to 2,4,5-trisubstituted oxazoles. Tetrahedron Lett., 44 (36), 6829-6832.
157. Fayol, A. and Zhu, J. (2004) Synthesis of polysubstituted 4,5,6,7 -tetrahydrofuro[2,3-c]pyridines by a novel multicomponent reaction. Org. Lett., 6 (1), 115-118.
158. Cuny, G., Gámez-Montano, R., and Zhu, J. (2004) Truncated diastereoselective Passerini reaction, a rapid construction of polysubstituted oxazole and peptides having an α-hydroxy-β-amino acid component. Tetrahedron, 60 (22), 4879-4885.
159. Fayol, A., Housseman, C., Sun, X., Janvier, P., Bienaymé, H., and Zhu, J. (2005)) Synthesis of α-isocyano-α -alkyl(aryl)acetamides and their use in the multicomponent synthesis of 5-aminooxazole, pyrrolo[3,4-b]pyridin-5 -one and 4,5,6,7-tetrahydrofuro[2,3-c] pyridine. Synthesis, (1), 161-165.
160. Pirali, T., Tron, G.C., and Zhu, J. (2006) One-pot synthesis of macrocycles by a tandem three-component reaction and intramolecular [3 + 2] cycloaddition. Org. Lett., 8 (18), 4145-4148.
161. Mishchenco, V.V., Itov, Z.I., L ' vova, S.D., Shostakovskaya, G.K., and Gunar, V.I. (1988) Synthesis of 4-methyl-5-propoxy-oxazoles from propyl α-isocyanopropionate. Pharm. Chem. J., 22 (7), 568-572.
162. Elders, N., Ruijter, E., de Kanter, F.J.J., Janssen, E., Lutz, M., Spek, A.L., and Orru, R.V.A. (2009) A multicomponent reaction towards N-(cyanomethyl) amides. C hem. Eur. J., 15 (25), 6096-6099.
163. Elders, N., Ruijter, E., de Kanter, F.J.J., Groen, M.B., and Orru, R.V.A. (2008) Selective formation of 2-imidazolines and 2-substituted oxazoles by using a three-component reaction. Chem. Eur. J., 14 (16), 4961-4973.
164. Elders, N. (2010) Multicomponent Approaches to Molecular Diversity & Complexity. PhD Thesis, VU University Amsterdam, the Netherlands.
165. Ganem, B. (2009) Strategies for innovation in multicomponent reaction design. Acc. Chem. Res., 42 (3), 463-471.
166. Ruijter, E., Scheffelaar, R., and Orru, R.V.A. (2011) Mehrkomponentenreaktionen als Weg zu molekularer Komplexität und Diversität. A ngew. Chem., 123 (28), 6358-6371.
167. Ruijter, E., Scheffelaar, R., and Orru, R.V.A. (2011) Multicomponent reaction design in the quest for molecular diversity and complexity. A ngew. Chem. Int. Ed., 50 (28), 6324-6346.
168. Xia, Q. and Ganem, B. (2002) Metal -promoted variants of the Passerini reaction leading to functionalized heterocycles. O rg. Lett., 4 (9), 1631-1634.
169. Pirali, T., Tron, G.C., Masson, G., and Zhu, J. (2007) Ammonium chloride promoted three-component synthesis of 5-iminooxazoline and its subsequent transformation to macrocyclodepsipeptide. O rg. Lett., 9 (25), 5275-5278.
170. Fayol, A. and Zhu, J. (2005) Three -component synthesis of polysubstituted 6-azaindolines and its tricyclic derivatives. Org. Lett., 7 (2), 239-242.
171. Bon, R.S., Hong, C., Bouma, M.J., Schmitz, R.F., de Kanter, F.J.J., Lutz, M., Spek, A.L., and Orru, R.V.A. (2003) Novel multicomponent reaction for the combinatorial synthesis of 2-imidazolines. Org. Lett., 5 (20), 3759-3762.
172. Bon, R.S., van Vliet, B., Sprenkels, N.E., Schmitz, R.F., de Kanter, F.J.J., Stevens, C.V., Swart, M., Bickelhaupt, F.M., Groen, M.B., and Orru, R.V.A. (2005) Multicomponent synthesis of 2-imidazolines. J. Org. Chem., 70 (9), 3542-3553.
173. Elders, N., Schmitz, R.F., de Kanter, F.J.J., Ruijter, E., Groen, M.B., and Orru, R.V.A. (2007) A resource-efficient and highly flexible procedure for a three-component synthesis of 2 -imidazolines. J. Org. Chem., 72 (16), 6135-6142.
174. Bon, R.S., de Kanter, F.J.J., Lutz, M., Spek, A.L., Jahnke, M.C., Hahn, F.E., Groen, M.B., and Orru, R.V.A. (2007) Multicomponent synthesis of N-heterocyclic carbene complexes. Organometallics, 26 (15), 3639-3650.
175. Strassberger, Z., Mooijman, M., Ruijter, E., Alberts, A.H., de Graaff, C., Orru, R.V.A., and Rothenberg, G. (2010) A facile route to ruthenium-carbene complexes and their application in furfural hydrogenation. Appl. Organomet. Chem., 24 (2), 142-146.
176. Strassberger, Z., Mooijman, M., Ruijter, E., Alberts, A.H., Maldonado, A.G., Orru, R.V.A., and Rothenberg, G. (2010) Finding furfural hydrogenation catalysts via predictive modelling. Adv. Synth. Catal., 352 (13), 2201-2210.
177. Vassilev, L.T., Vu, B.T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., Fotouhi, N., and Liu, E.A. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 303 (5659), 844-848.
178. Bon, R.S., Sprenkels, N.E., Koningstein, M.M., Schmitz, R.F., de Kanter, F.J.J., Dömling, A., Groen, M.B., and Orru, R.V.A. (2008) Efficient C2 functionalisation of 2 H-2-imidazolines. Org. Biomol. Chem., 6 (1), 130-137.
179. Srivastava, S., Beck, B., Wang, W., Czarna, A., Holak, T.A., and Dömling, A. (2009) Rapid and efficient hydrophilicity tuning of p53/mdm2 antagonists. J. Comb. Chem., 11 (4), 631-639.
180. Mironov, M.A. (2006) Design of multi-component reactions: from libraries of compounds to libraries of reactions. QSAR Comb. Sci., 25 (5-6), 423-431.
181. Dömling, A. and Ugi, I. (1993) Die siebenkomponentenreaktion. Angew. Chem., 105 (4), 634-635.
182. Dömling, A. and Ugi, I. (1993) The seven-component reaction. Angew. Chem. Int. Ed., 32 (4), 563-564.
183. Dömling, A., Herdtweck, E., and Ugi, I. (1998) MCR V: the seven-component reaction. Acta Chem. Scand., 52 (1), 107-113.
184. Elders, N., van der Born, D., Hendrickx, L.J.D., Timmer, B.J.J., Krause, A., Janssen, E., de Kanter, F.J.J., Ruijter, E., and Orru, R.V.A. (2009) The efficient one-pot reaction of up to eight components by the union of multicomponent reactions. Angew. Chem., 121 (32), 5970-5973.
185. Elders, N., van der Born, D., Hendrickx, L.J.D., Timmer, B.J.J., Krause, A., Janssen, E., de Kanter, F.J.J., Ruijter, E., and Orru, R.V.A. (2009) Angew. Chem. Int. Ed., 48 (32), 5856-5859.
186. Paravidino, M., Bon, R.S., Scheffelaar, R., Vugts, D.J., Znabet, A., Schmitz, R.F., de Kanter, F.J.J., Lutz, M., Spek, A.L., Groen, M.B., and Orru, R.V.A. (2006) Diastereoselective multicomponent synthesis of dihydropyridones with an isocyanide functionality. Org. Lett., 8 (23), 5369-5372.
187. Scheffelaar, R., Paravidino, M., Znabet, A., Schmitz, R.F., de Kanter, F.J.J., Lutz, M., Spek, A.L., Fonseca Guerra, C., Bickelhaupt, F.M., Groen, M.B., Ruijter, E., and Orru, R.V.A. (2010) Scope and limitations of an efficient four -component reaction for dihydropyridin -2-ones. J. Org. Chem., 75 (5), 1723-1732.
188. Paravidino, M., Scheffelaar, R., Schmitz, R.F., de Kanter, F.J.J., Groen, M.B., Ruijter, E., and Orru, R.V.A. (2007) A flexible six-component reaction to access constrained depsipeptides based on a dihydropyridinone core. J. Org. Chem., 72 (26), 10239-10242.
189. Scheffelaar, R., Paravidino, M., Muilwijk, D., Lutz, M., Spek, A.L., de Kanter, F.J.J., Orru, R.V.A., and Ruijter, E. (2009) A novel three-component reaction toward dihydrooxazolopyridines. Org. Lett., 11 (1), 125-128.
190. Scheffelaar, R., Klein Nijenhuis, R.A., Paravidino, M., Lutz, M., Spek, A.L., Ehlers, A.W., de Kanter, F.J.J., Groen, M.B., Orru, R.V.A., and Ruijter, E. (2009) Synthesis of conformationally constrained peptidomimetics using multicomponent reactions. J. Org. Chem., 74 (2), 660-668.
191. den Heeten, R., van der Boon, L., Broere, D.L.J., Janssen, E., de Kanter, F.J.J., Ruijter, E., and Orru, R.V.A. (2011) Concise synthesis of highly substituted benzo[a]quinolizines by a multicomponent reaction/ allylation/heck reaction sequence. Eur. J. Org. Chem., 275-280.