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Synlett 2002(12): 1991-1994
DOI: 10.1055/s-2002-35590
LETTER
© Georg Thieme Verlag Stuttgart · New York

‘Safety-Catch’ Propargyl-Based Linker Strategy for the Immobilization of Amines and Carboxylic Acids in SPOS

Maren Fürst, Karola Rück-Braun*
Technische Universität Berlin, Institut für Chemie, Straße des 17. Juni 135, 10623 Berlin, Germany
Fax: +49(30)31479651; e-Mail: krueck@chem.tu-berlin.de;
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Publikationsverlauf

Received 9 August 2002
Publikationsdatum:
20. November 2002 (online)

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Abstract

Integral propargyl alcohol and propargyl chloroformate linkers were developed for a ‘safety-catch’ acid-sensitive linker strategy. The syntheses of the integral propargyl linkers were achieved by direct conversion of the solid support starting from Merrifield resin, hydroxymethylpolystyrene or 4-bromopolystyrene. Amines and carboxylic acids have been coupled and released to demonstrate that transformation of the propargyl units to cobalt carbonyl complexes facilitates the cleavage under mild acidic conditions in high purity.

Key words

alkyne complexes - cobalt - linker - palladium - solid-phase

    References

  • 1a Früchtel JS. Jung G. Angew. Chem., Int. Ed. Engl.  1996,  35:  17 
    CrossrefGoogle Scholar
  • 1b Balkenhohl F. von dem Busche-Hünnefeld C. Lansky A. Zechel C. Angew. Chem., Int. Ed. Engl.  1996,  35:  2288 
    CrossrefGoogle Scholar
  • 1c Gulliver F. Orain D. Bradley M. Chem. Rev.  2000,  100:  2091 
    CrossrefGoogle Scholar
  • 1d Comely AC. Gibson SE. Angew. Chem. Int. Ed.  2001,  40:  988 
    CrossrefGoogle Scholar
  • 2 Pátek M. Lebl M. Biopolymers  1998,  47:  353 
    CrossrefGoogle Scholar
  • 3a Kenner GW. McDermott JR. Sheppard RC. J. Chem. Soc., Chem. Commun.  1971,  636 
    CrossrefGoogle Scholar
  • 3b Backes BJ. Virgilio AA. Ellman JA. J. Am. Chem. Soc.  1996,  118:  3055 ; and literature cited therein
    CrossrefGoogle Scholar
  • 3c Yang L. Moriello G. Tetrahedron Lett.  1999,  40:  8197 
    CrossrefGoogle Scholar
  • 4 Maclean D. Hale R. Chen M. Org. Lett.  2001,  3:  2977 
    CrossrefGoogle Scholar
  • 5a Flanigan E. Marshall DL. Tetrahedron Lett.  1970,  2403 
    CrossrefGoogle Scholar
  • 5b Marshall DL. Liener IE. J. Org. Chem.  1970,  35:  867 ; and literature cited therein
    CrossrefGoogle Scholar
  • 5c Gayo LM. Suto MJ. Tetrahedron Lett.  1997,  38:  211 ; and literature cited therein
    CrossrefGoogle Scholar
  • 6a Pátek M. Lebl M. Tetrahedron Lett.  1991,  32:  3891 
    CrossrefGoogle Scholar
  • 6b Brik A. Keinan E. Dawson PE. J. Org. Chem.  2000,  65:  3829 
    CrossrefGoogle Scholar
  • 7 Nicolaou KC. Wissinger N. Hughes R. Smethurst C. Cho SY. Angew. Chem. Int. Ed.  2000,  39:  1084 
    CrossrefGoogle Scholar
  • 8 Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  Wiley; New York: 1999. 
    Google Scholar
  • 9 Magnus P. Ladlow M. Elliott J. Kim CS. J. Chem. Soc., Chem. Commun.  1989,  518 
    CrossrefGoogle Scholar
  • 10a Fukase Y. Fukase K. Kusumoto S. Tetrahedron Lett.  1999,  40:  1169 
    CrossrefGoogle Scholar
  • 10b Fukase Y. Fukase K. Kusumoto S. In Peptide Science   Fuji N. The Japanese Peptide Society; Japan: 1999. 
    CrossrefGoogle Scholar
  • 11 Kusumoto S, and Fukase K. inventors; Jpn. Kokai Tokkyo Koho JP 2000  186,050.  ; Chem. Abstr. 2000, 133, 58364
  • 12 Kusumoto S, and Fukase K. inventors; Jpn. Kokai Tokkyo Koho JP 2000  186,049.  ; Chem. Abstr. 2000, 133, 58365
  • In the past a number of other cleavage protocols have been developed and examined in orthogonal protecting group strategies:
  • 13a H2/Pd: Cranddall JK. Keyton DJ. Kohne J. J. Org. Chem.  1968,  33:  3655 
    CrossrefGoogle Scholar
  • 13b See also: Southard GL. Zaborowsky BR. Pettee JM. J. Am. Chem. Soc.  1971,  93:  3302 
    CrossrefGoogle Scholar
  • 13c Pd(II), Bu3SnH: Zhang HX. Guibé F. Balavoine G. Tetrahedron Lett.  1988,  29:  619 
    CrossrefGoogle Scholar
  • 13d See further: Zhang HX. Guibé F. Balavoine G. Tetrahedron Lett.  1988,  29:  623 
    CrossrefGoogle Scholar
  • 13e Co2(CO)8, DMSO: Alcaide B. Pérez-Castells J. Sánchez-Vigo B. Sierra MA. J. Chem. Soc., Chem. Commun.  1994,  587 
    CrossrefGoogle Scholar
  • 13f [MoS4]2- and ultrasound in the case of the deprotection of amines: Sinha S. Ilankumaran P. Chandrasekaran S. Tetrahedron Lett.  1999,  40:  771 
    CrossrefGoogle Scholar
  • 13g See also: Ilankumaran P. Manoj N. Chandrasekaran S. Chem. Commun.  1996,  1957 
    CrossrefGoogle Scholar
  • 13h Low valent titanium: Rele S. Talukdar S. Banerji A. Tetrahedron Lett.  1999,  40:  767 
    CrossrefGoogle Scholar
  • 13i Kariyone K, and Yazawa T. inventors; Japan. Kokai JP  49011202. SeO2: ; Chem. Abstr. 1974, 81, 120227
    CrossrefGoogle Scholar
  • 14a Ziegler FE. Tung JS. J. Org. Chem.  1991,  56:  6530 
    CrossrefGoogle Scholar
  • 14b Crisp GT. Gore J. Tetrahedron  1997,  53:  1505 
    CrossrefGoogle Scholar
  • 15 Nagaoka H. Kishi Y. Tetrahedron  1981,  37:  3873 
    CrossrefGoogle Scholar
  • 16 Analogous preparation to the oxidation of Wang resin is described by: Yan B. Sun Q. Wareing JR. Jewell CF. J. Org. Chem.  1996,  61:  8765 
    Google Scholar
  • 17 Frechet JM. Schuerch C. J. Am. Chem. Soc.  1971,  93:  492 
    CrossrefGoogle Scholar
  • The structures of all non-polymeric compounds have been characterized by NMR, IR and elemental analysis or HRMS. The synthesis of compound 12 was carried out as follows:
  • 19a

    PPh3 (6 equiv), CCl4 (3 equiv), -20 °C, 25 min to 0 °C, 16 h, CH2Cl2, 92%;

    Google Scholar
  • 19b

    n-BuLi (1.6 M solution in hexane, 2 equiv), -78 °C, 5 h, THF, 71%;

    Google Scholar
  • 19c

    n-BuLi (1.6 M solution in hexane, 1.1 equiv), -78 °C to r.t., 19.5 h, THF, 74%;

    Google Scholar
  • 19d

    DIBALH (1 M in Toluol, 2 equiv), -78 °C to r.t., 16 h, quant.
    Compound 12: 1H NMR (200 MHz, CDCl3): δ [ppm] = 7.43-7.29 (m, 7 H, C-Harom.), 6.92-6.87 (m, 2 H, C-Harom.), 5.04 (s, 2 H, O-CH2), 4.46 (s, 2 H, CH2-OH), 1.78 (br s, 1 H, CH2-OH). 13C NMR (50.3 MHz, CDCl3): δ [ppm] = 158.97 (O-Carom.), 136.56 (CH2-Carom.), 133.22, 128.66, 128.14, 127.50, 114.89 (Carom.), 86.00 (CºC), 85.64 (CºC), 70.05 (CH2-OBn), 51.73 (CH2-OH); one quaternary signal of the aromatic region is overlapped by the adjacent tertiary signal. Elemental analysis: C16H14O2 (238.27 g/mol) calcd: C, 80.65; H, 5.92. Found: C, 80.58; H, 6.05. MS (FD): m/z = 238.5 (100.00), 239.5 (16.15), 240.6 (1.60).

    Google Scholar
  • 20 Although the solution-phase reaction conditions were not directly applicable to the solid support, the combined procedures proved to be advantageous during characterization of the resins by IR-spectroscopy: Grice P. Leuch AG. Ley SV. Massi A. Mynett DM. J. Comb. Chem.  2000,  2:  491 
    CrossrefGoogle Scholar
  • 21 Chan KS. Yeung ML. Chan W. Wang R.-J. Mak TCW. J. Org. Chem.  1995,  60:  1741 
    CrossrefGoogle Scholar
  • 22 Wadsworth DH. Geer SM. Detty MR. J. Org. Chem.  1987,  52:  3662 
    CrossrefGoogle Scholar
  • 23a Debono M. Turner WW. LaGrandeur L. Burkhardt FJ. Nissen JS. Nichols KK. Rodriguez MJ. Zweifel MJ. Zeckner DJ. Gordee RS. Tang J. Parr TR. J. Med. Chem.  1995,  38:  3271 
    CrossrefGoogle Scholar
  • 23b Crisp GT. Turner PD. Stephens KA. J. Organomet. Chem.  1998,  570:  219 
    CrossrefGoogle Scholar
  • For example:
  • 24a Thorand S. Krause N. J. Org. Chem.  1998,  63:  8551 
    CrossrefGoogle Scholar
  • 24b Glase SA. Akunne HC. Heffner TG. Jaen JC. MacKenzie RG. Meltzer LT. Pugsley TA. Smith SJ. Wiese LD. J. Med. Chem.  1996,  39:  3179 
    CrossrefGoogle Scholar
  • 26 Nicholas KM. Acc. Chem. Res.  1987,  20:  207 
    Google Scholar
18

All resins prepared have been characterized by IR spectro-
scopy and by elemental analysis before and after immobili-zation [resin 1: nitrogen analysis (route A), bromine and nitrogen analysis (route B); resin 2: chlorine and nitrogen analysis] as well as Fmoc-calibration for resin 1.

25

The in situ deprotection protocol of Y. Fukase, K. Fukase, S. Kusumoto, [10] when applied to propargyloxycarbonyl-protected phenylalanine methylester on 1.5 mmol scale, resulted in a product mixture and unsatisfactory product purity.