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Synthesis 2011(24): 3929-3953  
DOI: 10.1055/s-0031-1289590
REVIEW
© Georg Thieme Verlag Stuttgart ˙ New York

Supported Synthesis of Halogenated Organic Compounds

Sophie Boldona, Ida S. R. Stenhagena, Jane E. Mooreb, Sajinder K. Luthrac, Véronique Gouverneur*a
a Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK
Fax: +44(1865)275644; e-Mail: veronique.gouverneur@chem.ox.ac.uk;
b AstraZeneca UK, Alderley Park, Cheshire, SK10 4TG, UK
c GE Healthcare, The Grove Centre, White Lion Road, Amersham, HP7 9LL, UK
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Publication History

Received 23 August 2011
Publication Date:
08 November 2011 (online)

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Abstract

Halogenated organic compounds are highly sought after in a wide variety of fields, for example synthetic and medicinal chemistry as well as materials science. The supported synthesis of organohalogens has been extensively developed in the field of imaging where rapid purification of radiotracers containing isotopes with short half-lives is of great importance. Electrophilic and nucleophilic halogenation occurs upon cleavage from the support and the desired labeled product is readily separated from contaminants. This review provides a discussion as to how supported synthetic routes have facilitated the preparation of halogenated compounds.

1 Introduction

2 Halogenation of Supported Precursors

2.1 Fluorination

2.2 Chlorination

2.3 Bromination

2.4 Iodination

3 Conclusion

Key words

halogenation - solid support - fluorous - radiochemistry - detagging

    References

  • For reviews on solid-phase synthesis see:
  • 1a Guillier F. Orain D. Bradley M. Chem. Rev.  2000,  100:  2091 
    Search in Google Scholar
  • 1b Bräse S. Dahmen S. Chem. Eur. J.  2000,  6:  1899 
    Search in Google Scholar
  • 1c Gil C. Bräse S. Curr. Opin. Chem. Biol.  2004,  8:  230 
    Search in Google Scholar
  • 1d Bräse S. Acc. Chem. Res.  2004,  37:  805 
    Search in Google Scholar
  • 1e Scott PJH. Steel PG. Eur. J. Org. Chem.  2006,  2251 
  • 1f Merrifield RB. J. Am. Chem. Soc.  1963,  85:  2149 
    Search in Google Scholar
  • 2a Gribble GW. Acc. Chem. Res.  1998,  31:  141 
    Search in Google Scholar
  • 2b Gribble GW. J. Chem. Educ.  2004,  81:  1441 
    Search in Google Scholar
  • 2c O’Hagan D. Harper DB. J. Fluorine Chem.  1999,  100:  127 
    Search in Google Scholar
  • 2d Gribble GW. Naturally Occurring Organohalogen Compounds - A Comprehensive Update   Springer-Verlag; Vienna: 2010. 
  • For reviews on fluorine in medicinal chemistry see:
  • 3a Böhm H.-J. Banner D. Bendels S. Kansy M. Kuhn B. Müller K. Obst-Sander U. Stahl M. ChemBioChem  2004,  5:  637 
    Search in Google Scholar
  • 3b Müller K. Faeh C. Diederich F. Science  2007,  317:  1881 
    Search in Google Scholar
  • 3c Purser S. Moore PR. Swallow S. Gouverneur V. Chem. Soc. Rev.  2008,  37:  320 
    Search in Google Scholar
  • 3d Hagmann WK. J. Med. Chem.  2008,  51:  4359 
    Search in Google Scholar
  • 4a Thomas G. Medicinal Chemistry: An Introduction   Wiley; New York: 2000. 
  • 4b Metal-Catalyzed Cross-Coupling Reactions   2nd ed.:  de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004. 
  • 4c Corbet J.-P. Mignani G. Chem. Rev.  2006,  106:  2651 
    Search in Google Scholar
  • 4d Fairlamb I. Chem. Soc. Rev.  2007,  36:  1036 
    Search in Google Scholar
  • 4e Amii H. Uneyama K. Chem. Rev.  2009,  109:  2119 
    Search in Google Scholar
  • For reviews on molecular imaging see:
  • 5a Kugaya A. Fujita M. Innis RB. Ann. Nucl. Med.  2000,  14:  1 
    Search in Google Scholar
  • 5b Schyler DJ. Ann. Acad. Med. Singapore  2004,  33:  146 
    Search in Google Scholar
  • 5c Wester H.-J. Clin. Cancer Res.  2007,  13:  3470 
    Search in Google Scholar
  • 5d Taki J. Matsunari I. Eur. J. Nucl. Med. Mol. Imaging  2007,  34:  S34 
    Search in Google Scholar
  • 5e Yamashina S. Yamazaki J. Eur. J. Nucl. Med. Mol. Imaging  2007,  34:  S62 
    Search in Google Scholar
  • 5f Ametamey SM. Honer M. Schubiger PA. Chem. Rev.  2008,  108:  1501 
    Search in Google Scholar
  • 5g Holland GN. Bottomley PA. Hinshaw WS.
    J. Magn. Reson.  1977,  28:  133 
    Search in Google Scholar
  • 5h Janjic JM. Ahrens ET. WIREs Nanomed. Nanobio.  2009,  1:  492 
    Search in Google Scholar
  • 6 Gladysz JA. Curran DP. Horvath IT. Handbook of Fluorous Chemistry   Wiley-VCH; Weinheim: 2004. 
  • For reviews on fluorous-phase synthesis see:
  • 7a Zhang W. Tetrahedron  2003,  59:  4475 
    Search in Google Scholar
  • 7b Zhang W. Chem. Rev.  2004,  104:  2531 
    Search in Google Scholar
  • 7c Dandapani S. QSAR Comb. Sci.  2006,  25:  681 
    Search in Google Scholar
  • 7d Zhang W. Curran DP. Tetrahedron  2006,  62:  11837 
    Search in Google Scholar
  • 7e Zhang W. Cai C. Chem. Commun.  2008,  5686 
  • 7f Curran DP. Science  2008,  321:  1645 
    Search in Google Scholar
  • 7g Zhang W. Chem. Rev.  2009,  109:  749 
    Search in Google Scholar
  • 8a Pollack A. Roe DG. Pollack CM. Lu LFL. Thornback JR. J. Am. Chem. Soc.  1999,  121:  11593 
    Search in Google Scholar
  • 8b Dunn-Default R. Pollak A. Fitzgerald J. Thornback JR. Ballinger JR. Nucl. Med. Biol.  2000,  27:  803 
    Search in Google Scholar
  • 8c Maclean D. Zhu J. Chen M. Hale R. Satymurthy N. Barrio JR. J. Am. Chem. Soc.  2003,  125:  10168 
    Search in Google Scholar
  • 8d Mundwiler S. Candreia L. Hafliger P. Ortner K. Alberto R. Bioconjugate Chem.  2004,  15:  195 
    Search in Google Scholar
  • For reviews of ¹8F-radiochemistry see:
  • 9a Schirrmacher R. Wängler C. Schirrmacher E. Mini-Rev. Org. Chem.  2007,  4:  317 
    Search in Google Scholar
  • 9b Miller PW. Long NJ. Vilar R. Gee AD. Angew. Chem. Int. Ed.  2008,  47:  8998 
    Search in Google Scholar
  • 10 Cai L. Lu S. Pike VW. Eur. J. Org. Chem.  2008,  2853 
  • 11a Beuthien-Baumann B. Hamacher K. Oberdorfer F. Steinbach J. Carbohydr. Res.  2000,  327:  107 
    Search in Google Scholar
  • 11b Couturier O. Luxen A. Chatal J.-F. Vuillez J.-P. Rigo P. Hustinx R. Eur. J. Nucl. Med. Mol. Imaging  2004,  31:  1182 
    Search in Google Scholar
  • 12 Tooronigan SA. Mulholland GK. Jewett DM. Bachelor MA. Kilbourn MR. Nucl. Med. Biol.  1990,  17:  273 
    Search in Google Scholar
  • 13 Kuge Y. Nishijima K. Nagatsu K. Seki K. Ohkura K. Tanaka A. Sasaki M. Tsukamoto E. Tamaki N. Nucl. Med. Biol.  2002,  29:  275 
    Search in Google Scholar
  • 14 Ohsaki K. Endo Y. Yamazaki S. Tomoi M. Iwata R. Appl. Radiat. Isot.  1998,  49:  373 
    Search in Google Scholar
  • 15 Tang G. Wang M. Tang X. Luo L. Gan M. Nucl. Med. Biol.  2003,  30:  509 
    Search in Google Scholar
  • 16 Tang G. Wang M. Tang X. Luo L. Gan M. Appl. Radiat. Isot.  2003,  58:  685 
    Search in Google Scholar
  • 17 Olah GA. Li XY. Synlett  1990,  267 
  • 18 Sket B. Zupan M. Zupet P. Tetrahedron  1984,  40:  1603 
    Search in Google Scholar
  • 19 Brown LJ. Bouvet DR. Champion S. Gibson AM. Hu Y. Jackson A. Khan I. Ma N. Millot N. Wadsworth H. Brown RCD. Angew. Chem. Int. Ed.  2007,  46:  941 
    Search in Google Scholar
  • 20 Brown LJ. Ma N. Bouvet DR. Champion S. Gibson AM. Gibson AM. Hu Y. Jackson A. Khan I. Millot N. Topley AC. Wadsworth H. Wynn D. Brown RCD. Org. Biomol. Chem.  2009,  7:  564 
    Search in Google Scholar
  • 21 Gibson AM, Brown LJ, and Brown CD. inventors; PCT Int. Appl. WO  056725 A1. 
  • 22 Luthra SK, Brady F, Wadsworth HJ, Gibson AM, and Glaser ME. inventors; PCT Int. Appl. WO  002157 A1. 
  • 23 Brady F, Luthra SK, and Gibson AM. inventors; PCT Int. Appl. WO  056399 A2. 
  • 24a Shah A. Pike VW. Widdowson DA. J. Chem. Soc. Perkin Trans. 1  1998,  2043 
  • 24b Ermert J. Hocke C. Ludwig T. Gail R. Coenen HH. J. Labelled Compd. Radiopharm.  2004,  47:  429 
    Search in Google Scholar
  • 24c Zhang M.-R. Kumata K. Suzuki K. Tetrahedron Lett.  2007,  48:  8632 
    Search in Google Scholar
  • 25a Chun J.-H. Lu S. Lee Y.-S. Pike VW. J. Org. Chem.  2010,  75:  3332 
    Search in Google Scholar
  • 25b Brady F, Luthra SK, and Robins EG. inventors; PCT Int. Appl. WO  056400 A1. 
  • 26a Carroll L. Boldon S. Bejot R. Moore JE. Declerck J. Gouverneur V. Org. Biomol. Chem.  2010,  9:  136 
    Search in Google Scholar
  • 26b Bejot R. Fowler T. Carroll L. Boldon S. Moore JE. Declerck J. Gouverneur V. Angew. Chem. Int. Ed.  2009,  48:  586 
    Search in Google Scholar
  • 26c Bejot R, and Gouverneur V. inventors; PCT Int. Appl. WO  007363 A2. 
  • 27a Johnström PS. Stone-Elander S. Appl. Radiat. Isot.  1996,  47:  401 
    Search in Google Scholar
  • 27b Füchtner F. Preusche S. Mäding P. Zessin J. Steinbach J. Nuklearmedizin  2008,  3:  116 
    Search in Google Scholar
  • 28a Blom E. Karimi F. Långström B. J. Labelled Compd. Radiopharm.  2010,  53:  24 
    Search in Google Scholar
  • 28b Långström B, and Blom E. inventors; PCT Int. Appl. WO  106442 A1. 
  • 29 Blom E. Karimi F. Långström B. J. Labelled Compd. Radiopharm.  2009,  52:  504 
    Search in Google Scholar
  • 30 Långström B, and Kihlberg T. inventors; PCT Int Appl. WO  029633 A1. 
  • 31 Srinivasan A, Berndt M, Graham K, Friebe M, and Schmitt-Willich H. inventors; PCT Int. Appl. WO  000409 A2. 
  • 32a Långström B, and Farhad K. inventors; PCT Int. Appl. WO  073273. 
  • 32b Långstrom B, and Farhad K. inventors; PCT Int. Appl. US  0228060 A1. 
  • 33 Wiehn MS. Lindell SD. Bräse S. Angew. Chem. Int. Ed.  2008,  47:  8120 
    Search in Google Scholar
  • 34 Wiehn MS. Lindell SD. Bräse S. J. Comb. Chem.  2009,  11:  960 
    Search in Google Scholar
  • 35 Wiehn MS. Fürness D. Bräse S. J. Comb. Chem.  2009,  11:  982 
    Search in Google Scholar
  • 36 Döbele M. Vanderheiden S. Jung N. Bräse S. Angew. Chem. Int. Ed.  2010,  49:  5986 
    Search in Google Scholar
  • 37a Dollé F. Demphel S. Hinnen F. Fournier D. Vaufrey F. Crouzel C. J. Labelled Compd. Radiopharm.  1998,  41:  105 
    Search in Google Scholar
  • 37b Forsback S. Eskola O. Haaparanta M. Bergman J. Solin O. Radiochimica Acta  2008,  96:  845 
    Search in Google Scholar
  • 38 Kawai K. Channing MA. Kiesewetter DO. Eckelman WC. Nucl. Med. Biol.  1995,  22:  37 
    Search in Google Scholar
  • 39 Szajek LP. Channing MA. Eckelman WC. Appl. Radiat. Isot.  1998,  49:  795 
    Search in Google Scholar
  • 40 Luthra SK, Brady F, and Wadsworth HJ. inventors; PCT Int. Appl. WO  002489 A2. 
  • 41 Valliant JF. inventors; US  2004/0260073 A1. 
  • 42a Boldon SE. Moore JE. Gouverneur V. Chem. Commun.  2008,  3622 
  • 42b Thibaudeau S. Gouverneur V. Org. Lett.  2003,  5:  4891 
    Search in Google Scholar
  • 42c Pacheco MC. Purser S. Gouverneur V. Chem. Rev.  2008,  108:  1943 
    Search in Google Scholar
  • 42d Carroll L. McCullough S. Rees T. Claridge TDW. Gouverneur V. Org. Biomol. Chem.  2008,  6:  1731 
    Search in Google Scholar
  • 42e Lam Y.-h. Bobbio C. Cooper IR. Gouverneur V. Angew. Chem. Int. Ed.  2007,  46:  5106 
    Search in Google Scholar
  • 42f Purser S. Wilson C. Moore PR. Gouverneur V. Synlett  2007,  1166 
  • 42g Carroll L. Garcia L. Pacheco MC. Gouverneur V. Chem. Commun.  2006,  4113 
  • 42h Greedy B. Paris J.-M. Vidal T. Gouverneur V. Angew. Chem. Int. Ed.  2003,  42:  3291 
    Search in Google Scholar
  • 42i Pacheco MC. Gouverneur V. Org. Lett.  2005,  7:  1267 
    Search in Google Scholar
  • 42j Greedy B. Gouverneur V. Chem. Commun.  2001,  233 
  • 43 Pilot C. Dahmen S. Lauterwasser F. Bräse S. Tetrahedron Lett.  2001,  42:  9179 
    Search in Google Scholar
  • 44 Spivey AC. Diaper CM. Rudge AJ. Chem. Commun.  1999,  835 
  • 45a Nicolaou KC. Pastor J. Barluenga S. Winssinger N. Chem. Commun.  1998,  1947 
  • 45b Sheng S.-R. Huang X. Org. Prep. Proced. Int.  2003,  35:  383 
    Search in Google Scholar
  • 45c Sheng S.-R. Huang X. Tetrahedron Lett.  2001,  42:  9035 
    Search in Google Scholar
  • 45d Dewry DH. Coe DM. Poon S. Med. Res. Rev.  1999,  19:  97 
    Search in Google Scholar
  • 45e Nicolaou KC. Pfefferkorn JA. Cao GQ. Angew. Chem. Int. Ed.  2000,  39:  734 
    Search in Google Scholar
  • 46a Zajc B. Zupan M. Tetrahedron  1989,  45:  7869 
    Search in Google Scholar
  • 46b Zupan M. Šegatin N. Synth. Commun.  1994,  24:  2617 
    Search in Google Scholar
  • 46c Ley SV. Baxendale IR. Bream RN. Jackson PS. Leach AG. Longbottom DA. Nesi M. Scott JS. Storer RI. Taylor SJ. J. Chem. Soc., Perkin Trans. 1  2000,  3815 
  • 47 Han Y. Walker SD. Young RN. Tetrahedron Lett.  1996,  37:  2703 
    Search in Google Scholar
  • 48 Lee Y. Silverman RB. Tetrahedron  2001,  57:  5339 
    Search in Google Scholar
  • 49 Plunkett MJ. Ellman JA. J. Org. Chem.  1997,  62:  2885 
    Search in Google Scholar
  • 50 Spivey AC. Diaper CM. Adams H. Rudge AJ.
    J. Org. Chem.  2000,  65:  5253 
    Search in Google Scholar
  • 51 Rasmussen LK. Begtrup M. Ruhland T. J. Org. Chem.  2006,  71:  1230 
    Search in Google Scholar
  • 52a The Handbook of Radiopharmaceuticals: Radiochemistry and Applications   Welch MJ. Redvanly CS. Wiley; New York: 2002. 
  • 52b Langen K.-J. Ziemons K. Kiwit JCW. Herzog H. Kuwert T. Bock WJ. Stocklin G. Feinendegen LE. Muller-Gartner H.-W. J. Nucl. Med.  1997,  38:  517 
    Search in Google Scholar
  • 52c Weber W. Bartenstein P. Gross MW. Kinzel D. Daschner H. Feldmann HJ. Reidel G. Ziegler SI. Lumenta C. Molls M. Schwaiger M. J. Nucl. Med.  1997,  38:  802 
    Search in Google Scholar
  • 53 Young JK. Nelson JC. Moore JS. J. Am. Chem. Soc.  1994,  116:  10841 
    Search in Google Scholar
  • 54a Nelson JC. Young JK. Moore JS. J. Org. Chem.  1996,  61:  8160 
    Search in Google Scholar
  • 54b Zhang JS. Moore JS. Xu ZF. Aguirre RA. J. Am. Chem. Soc.  1992,  114:  2273 
    Search in Google Scholar
  • 55 Jones L. Schumm JS. Tour JM. J. Org. Chem.  1997,  62:  1388 
    Search in Google Scholar
  • 56 Hunt JA. Roush WR. J. Am. Chem. Soc.  1996,  118:  9998 
    Search in Google Scholar
  • 57 Takahashi T. Tomida S. Inoue H. Doi T. Synlett  1998,  1261 
  • 58 Creed D. Caldwell RA. Hiroyuki O. DeMarco DC.
    J. Am. Chem. Soc.  1977,  99:  278 
    Search in Google Scholar
  • 59 Xu W.-M. Wang Y.-G. Miao M.-Z. Huang X. Synthesis  2005,  2143 
  • 60 Sheng SR. Hu MG. Xin Q. Liu XL. Huang X. Chin. Chem. Lett.  2007,  18:  377 
    Search in Google Scholar
  • 61 Flanagan RJ. inventors; PCT US Appl. US  4874601. 
  • 62a Yong L. Yao M.-L. Kelly H. Green JF. Kabalka GW. Chem. Commun.  2010,  46:  2623 
    Search in Google Scholar
  • 62b Yong L. Yao M.-L. Kelly H. Green JF. Kabalka GW. J. Labelled Compd. Radiopharm.  2011,  54:  173 
    Search in Google Scholar
  • 63 Kawai K. Ohta H. Channing MA. Kubodera A. Eckelman WC. Appl. Radiat. Isot.  1996,  47:  37 
    Search in Google Scholar
  • 64 Brown SD. Armstrong RW. J. Org. Chem.  1997,  62:  7076 
    Search in Google Scholar
  • 65 Hunter DH. Culbert PA. Reactive Polymers  1993,  19:  247 
    Search in Google Scholar
  • 66a Hunter DH. Zhu X. J. Labelled Compd. Radiopharm.  1999,  42:  653 
    Search in Google Scholar
  • 66b Hunter DH, and Zhu X. inventors; PCT Int. Appl. WO  18053. 
  • 67 Kuschel S. Shea C. Fowler JS. Gifford AN. Bioconjugate Chem.  2011,  22:  406 
    Search in Google Scholar
  • 68 Kabalka GW. Namboodiri V. Akula MR. J. Labelled Compd. Radiopharm.  2001,  44:  921 
    Search in Google Scholar
  • 69a Donovan A. Forbes J. Dorff P. Schaffer P. Babich J. Valliant JF. J. Am. Chem. Soc.  2006,  128:  3536 
    Search in Google Scholar
  • 69b Valliant JF, Dorff P, and Chirakal R. inventors; PCT Int. Appl. WO  035744 A2. 
  • 69c Valliant JF, Dorff P, and Chirakal R. inventors; PCT US Appl. US  0005545 A1. 
  • 70 Donovan AC. Valliant JF. J. Org. Chem.  2009,  74:  8133 
    Search in Google Scholar
  • 71 Donovan AC. Valliant JF. Nucl. Med. Biol.  2008,  35:  741 
    Search in Google Scholar
  • 72 McIntee JW. Sundararajan C. Donovan AC. Kovacs MS. Capretta A. Valliant JF. J. Org. Chem.  2008,  73:  8236 
    Search in Google Scholar