Efficiency, Diversity, and Complexity with Multicomponent Reactions

Abstract

Multicomponent reactions (MCRs) are versatile syntheses for obtaining structurally diverse sets of complex scaffolds with high efficiency. As such, they can be attractive synthetic tools for the realization of diversity- and/or biology-oriented synthesis design strategies for focused libraries. In this account, we present an overview of our contribution to the design of novel MCRs to access a high level of molecular complexity and diversity. In addition, we demonstrate our biocatalysis/MCR sequences to obtain stereoenriched product scaffolds.

1 Introduction

2 The Build/Couple/Pair Strategy

3 Rational Design of Multicomponent Reactions

3.1 Single Reactant Replacement

3.2 Modular Reaction Sequences

3.3 Conditions-Based Divergence

3.4 The Combination of Multicomponent Reactions

4 Palladium-Catalyzed Isocyanide Reactions

5 The Quest for Stereoselective Multicomponent Reactions

6 Conclusion

Key words

biocatalysis - chemoselectivity - molecular complexity - molecular diversity - multicomponent reaction

• References

• 1a Sheldon RA. Green Chem. 2007; 9: 1273
• 1b Wender PA, Miller BL. Nature (London) 2009; 460: 197
• 1c Gaich T, Baran PS. J. Org. Chem. 2010; 75: 4657
• 2a Burke MD, Berger EM, Schreiber SL. Science (Washington, DC, U.S.) 2003; 302: 613
• 2b Burke MD, Schreiber SL. Angew. Chem. Int. Ed. 2004; 43: 46
• 2c Nielsen TE, Schreiber SL. Angew. Chem. Int. Ed. 2008; 47: 48
• 2d Slobbe P, Ruijter E, Orru RV. A. Med. Chem. Commun. 2012; 3: 1189
• 2e Akritopoulou-Zanze I. Curr. Opin. Chem. Biol. 2008; 12: 324
• 2f Ruijter E, Orru RV. A. Drug Discovery Today 2013; http://dx.doi.org/10.1016/j.ddtec.2012.10.012
• 3a Orru RV. A, de Greef M. Synthesis 2003; 1471
• 3b Dömling A. Chem. Rev. 2006; 106: 17
• 3c Ruijter E, Scheffelaar R, Orru RV. A. Angew. Chem. Int. Ed. 2011; 50: 6324
• 3d Zhu JP. Eur. J. Org. Chem. 2003; 1133
• 3e Sunderhaus JD, Martin SE. Chem. Eur. J. 2009; 15: 1300
• 3f Vlaar T, Ruijter E, Orru RV. A. Adv. Synth. Catal. 2011; 353: 809 ; and references cited therein
• 4a Coquerel Y, Boddaert T, Presset M, Mailhol D, Rodriguez J In Ideas in Chemistry and Molecular Sciences . Wiley-VCH; Weinheim: 2010: 187
• 4b Bonne D, Constantieux T, Coquerel Y, Rodriguez J. Chem. Eur. J. 2013; 19: 2218
• 5a Huebel K, Lessmann T, Waldmann H. Chem. Soc. Rev. 2008; 37: 1361
• 5b Kaiser M, Wetzel S, Kumar K, Waldmann H. Cell. Mol. Life Sci. 2008; 65: 1186
• 5c Kumar K, Waldmann H. Angew. Chem. Int. Ed. 2009; 58: 3224
• 5d Dömling A, Wang W, Wang K. Chem. Rev. 2012; 112: 3083
• 6 Kumagai N, Muncipinto G, Schreiber SL. Angew. Chem. Int. Ed. 2006; 45: 3635
• 7 Petasis NA, Goodman A, Zavialov IA. Tetrahedron 1997; 53: 16463
• 8 Muncipinto G, Moquist PN, Schreiber SL, Schaus SE. Angew. Chem. Int. Ed. 2011; 50: 8172
• 9 Wang HS, Ganesan A. Org. Lett. 1999; 1: 1647
• 10 Ruijter E, Garcia-Hartjes J, Hoffmann F, van Wandelen LT. M, de Kanter FJ. J, Janssen E, Orru RV. A. Synlett 2010; 2485
• 11a Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
• 11b Multicomponent Reactions . Zhu J, Bienaymé H. Wiley-VCH; Weinheim: 2006
• 12 Passerini M, Simone L. Gazz. Chim. Ital. 1921; 51: 126
• 13a Ugi I, Meyr R, Fetzer U, Steinbrückner C. Angew. Chem. 1959; 71: 386
• 13b Ugi I. Angew. Chem., Int. Ed. Engl. 1962; 1: 8 ; Angew. Chem. 1962, 74, 9
• 14 Xia Q, Ganem B. Org. Lett. 2002; 4: 1631
• 15 Sun XW, Janvier P, Zhao G, Bienaymé H, Zhu JP. Org. Lett. 2001; 3: 877
• 16 Elders N, Ruijter E, de Kanter FJ. J, Janssen E, Lutz M, Spek AL, Orru RV. A. Chem. Eur. J. 2009; 15: 6096
• 17 Groenendaal B, Ruijter E, Orru RV. A. Chem. Commun. 2008; 5474
• 18 Vugts DJ, Jansen H, Schmitz RF, de Kanter FJ. J, Orru RV. A. Chem. Commun. 2003; 2594
• 19 Vugts DJ, Koningstein MM, Schmitz RF, de Kanter FJ. J, Groen MB, Orru RV. A. Chem. Eur. J. 2006; 12: 7178
• 20 Lee K, Oh DY. Synthesis 1991; 213
• 21 Shin WS, Lee K, Oh DY. Tetrahedron Lett. 1995; 36: 281
• 22 Kiselyov AS. Tetrahedron Lett. 1995; 36: 9297
• 23 Kiselyov AS. Tetrahedron Lett. 2005; 46: 1663
• 24 Kiselyov AS, Smith L. Tetrahedron Lett. 2006; 47: 2611
• 25 Kiselyov AS. Tetrahedron Lett. 2006; 47: 2941
• 26 Groenendaal B, Ruijter E, de Kanter FJ. J, Lutz M, Spek AL, Orru RV. A. Org. Biomol. Chem. 2008; 6: 3158
• 27 Groenendaal B, Vugts DJ, Schmitz RF, de Kanter FJ. J, Ruijter E, Groen MB, Orru RV. A. J. Org. Chem. 2008; 73: 719
• 28 Biginelli P. Gazz. Chim. Ital. 1893; 23: 360
• 29 Glasnov TN, Vugts DJ, Koningstein MM, Desai B, Fabian WM. F, Orru RV. A, Kappe CO. QSAR Comb. Sci. 2006; 25: 509
• 30 Kruithof A, Ploeger ML, Janssen E, Helliwell M, de Kanter FJ. J, Ruijter E, Orru RV. A. Molecules 2012; 17: 1675
• 31 Paravidino M, Bon RS, Scheffelaar R, Vugts DJ, Znabet A, Schmitz RF, de Kanter FJ. J, Lutz M, Spek AL, Groen MB, Orru RV. A. Org. Lett. 2006; 8: 5369
• 32 Scheffelaar R, Paravidino M, Znabet A, Schmitz RF, de Kanter FJ. J, Lutz M, Spek AL, Guerra CF, Bickelhaupt FM, Groen MB, Ruijter E, Orru RV. A. J. Org. Chem. 2010; 75: 1723
• 33 den Heeten R, van der Boon LJ. P, Broere DL. J, Janssen E, de Kanter FJ. J, Ruijter E, Orru RV. A. Eur. J. Org. Chem. 2012; 275
• 34 Scheffelaar R, Nijenhuis RA. K, Paravidino M, Lutz M, Spek AL, Ehlers AW, de Kanter FJ. J, Groen MB, Orru RV. A, Ruijter E. J. Org. Chem. 2009; 74: 660
• 35 Fischer U, Mohler H, Schneider F, Widmer U. Helv. Chim. Acta 1990; 73: 763
• 36 Coffinier D, El Kaim L, Grimaud L, Ruijter E, Orru RV. A. Tetrahedron Lett. 2011; 52: 3023
• 37 Nef JU. Justus Liebigs Ann. Chem. 1892; 270: 267
• 38 Janvier P, Sun XW, Bienaymé H, Zhu JP. J. Am. Chem. Soc. 2002; 124: 2560
• 39 Janvier P, Bienaymé H, Zhu JP. Angew. Chem. Int. Ed. 2002; 41: 4291
• 40 Chebanov VA, Desenko SM. Chem. Heterocycl. Compd. (Engl. Transl.) 2012; 48: 566
• 41 Elders N, Ruijter E, de Kanter FJ. J, Groen MB, Orru RV. A. Chem. Eur. J. 2008; 14: 4961
• 42 Bon RS, Hong CG, Bouma MJ, Schmitz RF, de Kanter FJ. J, Lutz M, Spek AL, Orru RV. A. Org. Lett. 2003; 5: 3759
• 43 Grigg R, Lansdell MI, Thornton-Pett M. Tetrahedron 1999; 55: 2025
• 44 Bon RS, van Vliet B, Sprenkels NE, Schmitz RF, deKanter FJ. J, Stevens CV, Swart M, Bickelhaupt FM, Groen MB, Orru RV. A. J. Org. Chem. 2005; 70: 3542
• 45 Elders N, Schmitz RF, de Kanter FJ. J, Ruijter E, Groen MB, Orru RV. A. J. Org. Chem. 2007; 72: 6135
• 46 Bon RS, Sprenkels NE, Koningstein MM, Schmitz RF, de Kanter FJ. J, Dömling A, Groen MB, Orru RV. A. Org. Biomol. Chem. 2008; 6: 130
• 47 Bon RS, de Kanter FJ. J, Lutz M, Spek AL, Jahnke MC, Hahn FE, Groen MB, Orru RV. A. Organometallics 2007; 26: 3639
• 48 Strassberger Z, Mooijman M, Ruijter E, Alberts AH, de Graaff C, Orru RV. A, Rothenberg G. Appl. Organomet. Chem. 2010; 24: 142
• 49 Strassberger Z, Mooijman M, Ruijter E, Alberts AH, Maldonado AG, Orru RV. A, Rothenberg G. Adv. Synth. Catal. 2010; 352: 2201
• 50 Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA. Science 2004; 303: 844
• 51 Dömling A. Curr. Opin. Chem. Biol. 2000; 4: 318
• 52 Asinger F, Thiel M. Angew. Chem. 1958; 70: 667
• 53 Dömling A, Ugi I. Angew. Chem., Int. Ed. Engl. 1993; 32: 563
• 54 Portlock DE, Ostaszewski R, Naskar D, West L. Tetrahedron Lett. 2003; 44: 603
• 55 Paravidino M, Scheffelaar R, Schmitz RF, De Kanter FJ. J, Groen MB, Ruijter E, Orru RV. A. J. Org. Chem. 2007; 72: 10239
• 56 Scheffelaar R, Paravidino M, Muilwijk D, Lutz M, Spek AL, de Kanter FJ. J, Orru RV. A, Ruijter E. Org. Lett. 2009; 11: 125
• 57 Haubner R, Finsinger D, Kessler H. Angew. Chem., Int. Ed. Engl. 1997; 36: 1374
• 58 Elders N, van der Born D, Hendrickx LJ. D, Timmer BJ. J, Krause A, Janssen E, de Kanter FJ. J, Ruijter E, Orru RV. A. Angew. Chem. Int. Ed. 2009; 48: 5856
• 59 Harriman GC. B. Tetrahedron Lett. 1997; 38: 5591
• 60 Shaabani A, Maleki A, Moghimi-Rad J. J. Org. Chem. 2007; 72: 6309
• 61a El Kaim L, Grimaud L, Oble J. Angew. Chem. Int. Ed. 2005; 44: 7961
• 61b El Kaim L, Gizolme M, Grimaud L, Oble J. J. Org. Chem. 2007; 72: 4169
• 62 Kosugi M, Ogata T, Tamura H, Sano H, Migita T. Chem. Lett. 1986; 1197
• 63 Saluste CG, Whitby RJ, Furber M. Angew. Chem. Int. Ed. 2000; 39: 4156
• 64 Vlaar T, Ruijter E, Znabett A, Janssen E, de Kanter FJ. J, Maes BU. W, Orru RV. A. Org. Lett. 2011; 13: 6496
• 65a Bienaymé H, Bouzid K. Angew. Chem. Int. Ed. 1998; 37: 2234
• 65b Blackburn C. Tetrahedron Lett. 1998; 39: 5469
• 65c Blackburn C, Guan B, Fleming P, Shiosaki K, Tsai S. Tetrahedron Lett. 1998; 39: 3635
• 65d Groebke K, Weber L, Mehlin F. Synlett 1998; 661
• 66 Vlaar T, Cioc RC, Mampuys P, Maes BU. W, Orru RV. A, Ruijter E. Angew. Chem. Int. Ed. 2012; 51: 13058
• 67 Van Baelen G, Kuijer S, Rycek L, Sergeyev S, Janssen E, de Kanter FJ. J, Maes BU. W, Ruijter E, Orru RV. A. Chem. Eur. J. 2011; 17: 15039
• 68a de Graaff C, Ruijter E, Orru RV. A. Chem. Soc. Rev. 2012; 41: 3969
• 68b Ramon DJ, Yus M. Angew. Chem. Int. Ed. 2005; 44: 1602
• 68c Bonne D, Coquerel Y, Constantieux T, Rodriguez J. Tetrahedron: Asymmetry 2010; 21: 1085
• 68d van Berkel SS, Bogels BG. M, Wijdeven MA, Westermann B, Rutjes FP. J. T. Eur. J. Org. Chem. 2012; 3543
• 69 Marson CM. Chem. Soc. Rev. 2012; 41: 7712
• 70 Kohler V, Bailey KR, Znabet A, Raftery J, Helliwell M, Turner NJ. Angew. Chem. Int. Ed. 2010; 49: 2182
• 71 Znabet A, Ruijter E, de Kanter FJ. J, Koehler V, Helliwell M, Turner NJ, Orru RV. A. Angew. Chem. Int. Ed. 2010; 49: 5289
• 72 El Kaim L, Gageat M, Gaultier L, Grimaud L. Synlett 2007; 500
• 73 Znabet A, Zonneveld J, Janssen E, De Kanter FJ. J, Helliwell M, Turner NJ, Ruijter E, Orru RV. A. Chem. Commun. 2010; 46: 7706
• 74 Martins MB, Carvalho I. Tetrahedron 2007; 63: 9923
• 75 Nicholson B, Lloyd GK, Miller BR, Palladino MA, Kiso Y, Hayashi Y, Neuteboom ST. C. Anti-Cancer Drugs 2006; 17: 25
• 76 Sinha S, Srivastava R, De Clereq E, Singh RK. Nucleosides, Nucleotides Nucleic Acids 2004; 23: 1815
• 77 Kwon OS, Park SH, Yun BS, Pyun YR, Kim CJ. J. Antibiot. 2000; 53: 954
• 78 Wiesner M, Revell JD, Wennemers H. Angew. Chem. Int. Ed. 2008; 47: 1871
• 79 Wiesner M, Neuburger M, Wennemers H. Chem. Eur. J. 2009; 15: 10103
• 80 Wiesner M, Upert G, Angelici G, Wennemers H. J. Am. Chem. Soc. 2010; 132: 6
• 81 Znabet A, Polak MM, Janssen E, de Kanter FJ. J, Turner NJ, Orru RV. A, Ruijter E. Chem. Commun. 2010; 46: 7918
• 82 Yip Y, Victor F, Lamar J, Johnson R, Wang QM, Glass JI, Yumibe N, Wakulchik M, Munroe J, Chen SH. Bioorg. Med. Chem. Lett. 2004; 14: 5007
• 83 Yip Y, Victor F, Lamar J, Johnson R, Wang QM, Barket D, Glass J, Jin L, Liu LF, Venable D, Wakulchik M, Xie CP, Heinz B, Villarreal E, Colacino J, Yumibe N, Tebbe M, Munroe J, Chen SH. Bioorg. Med. Chem. Lett. 2004; 14: 251
• 84 Znabet A, Blanken S, Janssen E, de Kanter FJ. J, Helliwell M, Turner NJ, Ruijter E, Orru RV. A. Org. Biomol. Chem. 2012; 10: 941
• 85 Cerulli V, Banfi L, Basso A, Rocca V, Riva R. Org. Biomol. Chem. 2012; 10: 1255