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Synthesis 2011(6): 954-960  
DOI: 10.1055/s-0030-1258428
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Practical One-Pot Double Functionalizations of Proline

Peter Huy, Hans-Günther Schmalz*
Department für Chemie, Universität zu Köln, Greinstr. 4, 50939 Köln, Germany
Fax: +49(221)4703064; e-Mail: schmalz@uni-koeln.de;
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Publikationsverlauf

Received 23 December 2010
Publikationsdatum:
10. Februar 2011 (online)

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Abstract

Solubilization of proline as the triethylammonium salt allows N-protection (as the Boc, Cbz or Moc derivative) and subsequent esterification or amidation of the carboxy terminus to be performed in an efficient one-pot fashion. Based on this concept, highly practical protocols were developed to prepare a series of proline derivatives (including Pro-Ser dipetides, Weinreb amides and N-protected proline esters), which are important intermediates, for instance, for the synthesis of proline-derived peptides, chiral reagents and catalysts for asymmetric synthesis.

Key words

proline derivatives - peptides - carbamates - N-protecting groups - solvent effects - coupling reagents

    References

  • Selected references:
  • 1a Gentilucci L. Cerisoli L. De Marco R. Tolomelli A. Tetrahedron Lett.  2010,  51:  2576 
    Google Scholar
  • 1b Dai N. Etzkorn FA. J. Am. Chem. Soc.  2009,  131:  13728 
    Google Scholar
  • 1c Chiba K. Sugihara M. Yoshida K. Mikami Y. Kim S. Tetrahedron  2009,  65:  8014 
    Google Scholar
  • 1d Heiser U, Niestroj AJ, and Schulz I. inventors; WO Patent 007415  A2. 
    Google Scholar
  • 1e Sun H. Martin C. Kesselring D. Keller R. Moeller KD. J. Am. Chem. Soc.  2006,  128:  13761 
    Google Scholar
  • 1f Pfeifer ME. Linden A. Robinson JA. Helv. Chim. Acta  1997,  80:  1513 
    Google Scholar
  • 1g Falorni M. Porcheddu A. Giacomelli G. Tetrahedron: Asymmetry  1996,  7:  1999 
    Google Scholar
  • Selected references:
  • 2a Woodin KS. Jamison TF. J. Org. Chem.  2007,  72:  7451 
    Google Scholar
  • 2b Ni Y. Zhao G. Ding Y. J. Chem. Soc., Perkin Trans. 1  2000,  3264 
    Google Scholar
  • 2c Sibi M. Christensen J. J. Org. Chem.  1999,  64:  6434 
    Google Scholar
  • 2d Céliméne C. Dhimane H. Lhommet G. Tetrahedron  1998,  54:  10457 
    Google Scholar
  • See, for example:
  • 3a Chena Z. Ye T. New J. Chem.  2006,  30:  518 
    Google Scholar
  • 3b Yokokawa F. Sameshima H. In Y. Minoura K. Ishida T. Shioiri T. Tetrahedron  2002,  58:  8127 
    Google Scholar
  • 4a Corey EJ. Bakshi RK. Shibata S. J. Am. Chem. Soc.  1987,  109:  5551 
    Google Scholar
  • 4b Corey EJ. Helal CJ. Angew. Chem. Int. Ed.  1998,  37:  1986 
    Google Scholar
  • 4c Stemmler RT. Synlett  2007,  997 
    Google Scholar
  • 5 Corey EJ. Angew. Chem. Int. Ed.  2002,  41:  1650 
    CrossrefPubMedGoogle Scholar
  • For recent reviews, see:
  • 6a Bertelsen S. Jørgensen KA. Chem. Soc. Rev.  2009,  38:  2178 
    Google Scholar
  • 6b MacMillan DWC. Nature (London)  2008,  455:  304 
    Google Scholar
  • 6c Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 
    Google Scholar
  • 7 Zaminer J. Brockmann C. Huy P. Opitz R. Reuter C. Beyermann M. Freund C. Müller M. Oschkinat H. Kühne R. Schmalz H.-G. Angew. Chem. Int. Ed.  2010,  49:  7111 
    CrossrefGoogle Scholar
  • 8a Anderson GW. McGregor AC. J. Am. Chem. Soc.  1957,  79:  6180 
    Google Scholar
  • 8b Kaname M. Mashige H. Yoshifuji S. Chem. Pharm. Bull.  2001,  49:  531 
    Google Scholar
  • 9a Takeda K. Akiyama A. Nakamura H. Takizawa Y. Mizuno Y. Takayanagi H. Harigaya Y. Synthesis  1994,  1063 
    Google Scholar
  • 9b Held I. Von Den Hoff P. Stephenson DS. Zipse H. Adv. Synth. Catal.  2008,  350:  1891 
    Google Scholar
  • 10 Hayashi Y. Matsuzawa M. Yamaguchi J. Yonehara S. Matsumoto Y. Shoji M. Hashizume D. Koshino H. Angew. Chem. Int. Ed.  2006,  45:  4593 
    CrossrefGoogle Scholar
  • To the best of our knowledge, the only one-step protocols for the synthesis of compounds of type 2 described so far lead to N-Moc (or N-Eoc)-protected proline esters; see:
  • 11a Kanth JVB. Perlasamy M. Synth. Commun.  1995,  25:  1523 
    Google Scholar
  • 11b Oliveira DF. Miranda PCML. Correia Carlos RD. J. Org. Chem.  1999,  64:  6646 
    Google Scholar
  • 14 Zhou ZH. Tang YL. Li KY. Liu B. Tang CC. Heteroat. Chem.  2003,  14:  603 
    CrossrefGoogle Scholar
  • 15a König W. Geiger R. Chem. Ber.  1970,  103:  788 
    Google Scholar
  • 15b Deng S. Taunton J. Org. Lett.  2005,  7:  299 
    Google Scholar
  • 17a Ho G.-J. Mathre DJ. J. Org. Chem.  1995,  60:  2271 
    Google Scholar
  • 17b Soloshonok VA. Ueki H. Jiang C. Cai C. Hruby VJ. Helv. Chim. Acta  2002,  85:  3616 
    Google Scholar
  • 18 Kim S. Lee JI. Kim YC. J. Org. Chem.  1985,  50:  560 
    CrossrefGoogle Scholar
  • 21 Mayr H. Ofial AR. Angew. Chem. Int. Ed.  2006,  45:  1844 ; and references cited therein
    CrossrefPubMedGoogle Scholar
  • 22 Beckett RP. Davies SG. Mortlock AA. Tetrahedron: Asymmetry  1992,  3:  123 
    CrossrefGoogle Scholar
  • 23 Gibson FS. Bergmeier SC. Rapoport H. J. Org. Chem.  1994,  59:  3216 
    CrossrefGoogle Scholar
  • 24 Anderson GW. Callahan FM. J. Am. Chem. Soc.  1960,  82:  3359 
    CrossrefGoogle Scholar
  • 25 Irie K. Ishida A. Nakamura T. Oh-ishi T. Chem. Pharm. Bull.  1984,  32:  2126 
    CrossrefGoogle Scholar
12

Protic solvents such as water or alcohols are rival nucleophiles.

13

The esterification step requires DMAP as a nucleophilic catalyst, which activates both Boc2O (to react with the carboxylate) and the resulting mixed anhydride (to react with t-BuOH); see ref. 9a.

16

DCC-mediated coupling of 10 in the presence of DMAP led to the isolation of 2e in only 48% yield, along with 21% of the tert-butyl ester 2b resulting from the reaction of 7a with tert-butyl alcohol.

19

Methyl ester 2j was synthesized in 93% yield with K2CO3 instead of Et3N.¹¹b

20

For example, the yield of tert-butyl ester 2k (Table  [²] , entry 9) dropped to 42% when MocCl was added undiluted.