Synthesis 2017; 49(05): 1009-1023
DOI: 10.1055/s-0036-1588681
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© Georg Thieme Verlag Stuttgart · New York

One-Step Synthesis of a Unique Molecular Platform for the Selective Functionalization of Calix[6]arenes

Roy Lavendommea, b, Volodymyr Malytskyia, Jeremy Vandermeerscha, Michel Luhmerb, Ivan Jabin*a
  • aLaboratoire de Chimie Organique, Université libre de Bruxelles (ULB), Avenue F. D. Roosevelt 50, CP160/06, 1050 Brussels, Belgium   Email: ijabin@ulb.ac.be
  • bLaboratoire de Résonance Magnétique Nucléaire Haute Résolution, Université libre de Bruxelles (ULB), Avenue F. D. Roosevelt 50, CP160/08, 1050 Brussels, Belgium
Further Information

Publication History

Received: 24 October 2016

Accepted after revision: 01 December 2016

Publication Date:
03 January 2017 (eFirst)

Abstract

High selectivity is crucial for the functionalization of macrocyclic platforms bearing multiple identical functions. In the case of calix[6]arenes, only a few examples of efficient homo-functionalization have been reported. Herein, we describe the one-step synthesis of a tri-differentiated calix[6]arene and its use as a key intermediate to selectively access various homo- and hetero-functionalization patterns. In combination with the ‘all-but-one’ carbamatation methodology, this unique building block gives access to sophisticated calix[6]arenes that, until now, were inaccessible.

Supporting Information

 
  • References

    • 2a Calixarenes and Beyond . Neri P, Sessler JL, Wang M.-X. Springer; Cham; 2016
    • 2b For a recent leading example in the field of cyclodextrins, see: Wang B, Zaborova E, Guieu S, Petrillo M, Guitet M, Blériot Y, Ménand M, Zhang Y, Sollogoub M. Nat. Commun. 2014; 5: 5354
  • 3 Lavendomme R, Zahim S, De Leener G, Inthasot A, Mattiuzzi A, Luhmer M, Reinaud O, Jabin I. Asian J. Org. Chem. 2015; 4: 710
    • 4a Casnati A, Arduini A, Ghidini E, Pochini A, Ungaro R. Tetrahedron 1991; 47: 2221
    • 4b Groenen LC, Ruël BH. M, Casnati A, Verboom W, Pochini A, Ungaro R, Reinhoudt DN. Tetrahedron 1991; 47: 8379
    • 4c Matvieiev YI, Boyko VI, Podoprigorina AA, Kalchenko VI. J. Inclusion Phenom. Macrocyclic Chem. 2008; 61: 89
    • 4d Shang S, Khasnis DV, Burton JM, Santini CJ, Fan M, Small AC, Lattman M. Organometallics 1994; 13: 5157

      For examples of calix[6]arene mono-functionalization, see:
    • 5a Janssen RG, Verboom W, Reinhoudt DN, Casnati A, Freriks M, Pochini A, Ugozzoli F, Ungaro R, Nieto PM, Carramolino M, Cuevas F, Prados P, de Mendoza J. Synthesis 1993; 380
    • 5b Janssen RG, Verboom W, Harkema S, Van Hummel GJ, Reinhoudt DN, Pochini A, Ungaro R, Prados P, de Mendoza J. J. Chem. Soc., Chem. Commun. 1993; 506
    • 5c Kanamathareddy S, Gutsche CD. J. Org. Chem. 1994; 59: 3871
    • 5d Santoyo-Gonzalez F, Torres-Pinedo A, Sanchez-Ortega A. J. Org. Chem. 2000; 65: 4409
    • 5e Semwal A, Bhattacharya A, Nayak SK. Tetrahedron 2002; 58: 5287
    • 5f Gong S, Wang W, Chen Y, Meng L, Wan T. New J. Chem. 2002; 26: 1827

    • For recent examples of selective mono-functionalization on the large rim, see:
    • 5g Inthasot A, Dang Thy M.-D, Lejeune M, Fusaro L, Reinaud O, Luhmer M, Colasson B, Jabin I. J. Org. Chem. 2014; 79: 1913
    • 5h Inthasot A, Brunetti E, Lejeune M, Ménard N, Prangé T, Fusaro L, Bruylants G, Reinaud O, Luhmer M, Jabin I, Colasson B. Chem. Eur. J. 2016; 22: 4855

      For examples of calix[6]arene di-functionalization, see:
    • 6a Neri P, Rocco C, Consoli GM. L, Piattelli M. J. Org. Chem. 1993; 58: 6535
    • 6b Otsuka H, Araki K, Shinkai S. J. Org. Chem. 1994; 59: 1542
    • 6c Ross H, Lüning U. Angew. Chem., Int. Ed. Engl. 1995; 34: 2555
    • 6d Wroblewki W, Brzozka Z, Janssen RG, Verboom W, Reinhoudt DN. New J. Chem. 1996; 20: 419
    • 6e Chen Y, Li J, Xin J, Zhong Z, Gong S, Lu X. Synth. Commun. 1999; 29: 705
    • 6f Li J, Chen Y, Lu X. Tetrahedron 1999; 55: 10365
    • 6g Chen Y.-K, Chen Y.-Y. Org. Lett. 2000; 2: 743
    • 6h Gong S.-L, Chen Y.-K, Li J, Duan H.-P, Chen Y.-Y. Chin. J. Chem. 2004; 22: 573
    • 6i Toda M, Kondo Y, Niimi T, Higuchi Y, Endo K, Hamada F. Collect. Czech. Chem. Commun. 2004; 69: 1381
    • 6j Yang F, Guo H, Lin J. Chem. J. Internet 2005; 7: P.42
    • 6k Li H, Chen Y, Tian D, Gao Z. J. Membr. Sci. 2008; 310: 431
    • 6l Yang F, Wu Y, Ye J, Guo H, Yan X. J. Macromol. Sci., Part A: Pure Appl. Chem. 2014; 51: 223
    • 6m Zahim S, Lavendomme R, Reinaud O, Luhmer M, Evano G, Jabin I. Org. Biomol. Chem. 2016; 14: 1950

      For examples of calix[6]arene tri-functionalization, see:
    • 7a Zheng Z.-B, Wu R.-T, Li J.-K, Sun Y.-F. Aust. J. Chem. 2008; 61: 537
    • 7b Neri P, Pappalardo S. J. Org. Chem. 1993; 58: 1048
    • 7c Saponar A, Silaghi-Dumitrescu I, Popovici E.-J, Popovici N. Stud. Univ. Babes-Bolyai Chem. 2007; 52: 67
    • 7d Saponar A, Popovici E.-J, Nemes G, Popovici N, Perhaita I, Silaghi-Dumitrescu I. Rev. Chim.-Bucharest 2011; 62: 596
    • 7e Neri P, Consoli GM. L, Cunsolo F, Piattelli M. Tetrahedron Lett. 1994; 35: 2795
    • 7f Le Gac S, Marrot J, Jabin I. Chem. Eur. J. 2008; 14: 3316
    • 7g Lejeune M, Picron JF, Mattiuzzi A, Lascaux A, De Cesco S, Brugnara A, Thiabaud G, Darbost U, Coquière D, Colasson B, Reinaud O, Jabin I. J. Org. Chem. 2012; 77: 3838
    • 7h Danjou P.-E, De Leener G, Cornut D, Moerkerke S, Mameri S, Lascaux A, Wouters J, Brugnara A, Colasson B, Reinaud O, Jabin I. J. Org. Chem. 2015; 80: 5084

      For examples of calix[6]arene tetra-functionalization, see:
    • 8a van Heijst J, Corda M, Lukin O. Polymer 2015; 70: 1
    • 8b Agrawal YK, Bhatt SK. Synth. Commun. 2007; 37: 551
    • 8c Chen Y.-Y, Chen Y.-K, Gong S.-L, Gao Z.-N. Chin. J. Chem. 2001; 19: 299
    • 8d Neri P, Foti M, Ferguson G, Gallagher JF, Kaitner B, Pons M, Molins MA, Giunta L, Pappalardo S. J. Am. Chem. Soc. 1992; 114: 7814
    • 8e Rogers JS, Gutsche CD. J. Org. Chem. 1992; 57: 3152
    • 8f Kim EJ, Ahn J, Lee H, Noh TH, Jung O.-S. Tetrahedron Lett. 2012; 53: 1240

      For examples of selectively hetero-functionalized calix[6]arene, see:
    • 9a Sénèque O, Reinaud O. Tetrahedron 2003; 59: 5563
    • 9b Rondelez Y, Li Y, Reinaud O. Tetrahedron Lett. 2004; 45: 4669
    • 9c Darbost U, Zeng X, Giorgi M, Jabin I. J. Org. Chem. 2005; 70: 10552
    • 9d Chen Y, Li H. New J. Chem. 2001; 25: 340
    • 9e Konrad S, Bolte M, Nather C, Luning U. Eur. J. Org. Chem. 2006; 4717
    • 10a Lavendomme R, Leroy A, Luhmer M, Jabin I. J. Org. Chem. 2014; 79: 6563
    • 10b Lavendomme R, Cragg PJ, Marcos PM, Luhmer M, Jabin I. Org. Lett. 2015; 17: 5690
  • 11 An 88% yield was obtained when the reaction was performed with 500 mg of X6H6 (1). A slightly lower yield (79%) was obtained on a multigram scale, mostly because a different work-up had to be used. See the experimental section.
  • 12 See the Supporting Information.
  • 13 Note that the chemical shift of the 13C-OH signal for the parent compound X6H6 (1) is much lower (i.e., 147.2 ppm) (CDCl3, 298 K), suggesting the presence of strong intramolecular H-bonds in the case of compound 3, see: Gutsche CD, Dhawan B, No KH, Muthukrishnan R. J. Am. Chem. Soc. 1981; 103: 3782
  • 14 X6H2Bac3K (3) is stable in the solid state at room temperature provided that it is kept free of residual traces of chlorinated solvents. Indeed, slow degradation of 3 in the solid state was observed over several days in the presence of traces of chlorinated solvents, which is likely due to the slow degradation of such solvents into hydrochloric acid. Besides, slow degradation was also observed in a stirred solution of 3 ([3] = 10 mM) in CH2Cl2 leading to the slow formation of di-carbamated p-t-Bu-calix[6]arenes over a few days. This was however attributed to the elimination reaction leading to the release of t-BuNCO (see the Supporting Information).
    • 15a de Mendoza J, Carramolino M, Cuevas F, Nieto PM, Prados P, Reinhoudt DN, Verboom W, Ungaro R, Casnati A. Synthesis 1994; 47
    • 15b Ciao R, Talotta C, Gaeta C, Neri P. Supramol. Chem. 2014; 26: 569
    • 15c De Rosa M, Soriente A, Concilio G, Talotta C, Gaeta C, Neri P. J. Org. Chem. 2015; 80: 7295
  • 16 Some signals are however still broadened at high T, preventing full assignment.
  • 17 The sensitivity of the Bac groups toward acidic conditions depends on the structure of the starting material. We thus had to use different conditions for the deprotection reactions described herein (i.e., reaction time, concentration of acid and/or water).
    • 18a Al-Saraierh H, Miller DO, Georghiou P. J. Org. Chem. 2005; 70: 8273
    • 18b Molad A, Goldberg I, Vigalok A. J. Am. Chem. Soc. 2012; 134: 7290
  • 19 Ménand M, Leroy A, Marrot J, Luhmer M, Jabin I. Angew. Chem. Int. Ed. 2009; 48: 5509

    • For examples in the field of calixarenes, see:
    • 20a Haino T, Harano T, Matsumura K, Fukazawa Y. Tetrahedron Lett. 1995; 36: 5793
    • 20b Wang J, Gutsche CD. J. Org. Chem. 2002; 67: 4423
    • 20c Podoprygorina G, Zhang J, Brusko V, Bolte M, Janshoff A, Böhmer V. Org. Lett. 2003; 5: 5071
    • 20d Tian X.-H, Chen C.-F. Chem. Eur. J. 2010; 16: 8072
    • 20e Fischer C, Stapf M, Seichter W, Weber E. Supramol. Chem. 2013; 25: 371
    • 20f Zhao Y, Markopoulos G, Swager TM. J. Am. Chem. Soc. 2014; 136: 10683
    • 20g Menon SR, Schmidt JA. R. Tetrahedron 2016; 72: 767

      For reactions combining dealkylation and de-tert-butylation, see:
    • 21a Guo-Yuan L, Qian L, Fang L, Xiao-Bin W. Chin. J. Chem. 2000; 18: 207
    • 21b Tian X.-H, Chen C.-F. Org. Lett. 2010; 12: 524
  • 22 Szumna A. Chem. Soc. Rev. 2010; 39: 4274
  • 23 Signal broadening, signal overlapping and/or low solubility prevented the observation of all the expected 13C NMR signals.