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Synthesis 2003(11): 1653-1656
DOI: 10.1055/s-2003-40875
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Practical Synthesis of α-Amino Ketones via Aryllithium Addition to N-Boc-α-Amino Acids

Alan S. Florjancic*, George S. Sheppard
Abbott Laboratories, Global Pharmaceutical Products Research and Development, R4PM AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Fax: +1(847)9355466; e-Mail: alan.florjancic@abbott.com;
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Publication History

Received 7 May 2003
Publication Date:
25 July 2003 (online)

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Abstract

The reaction of N-Boc-α-amino acids with aryllithium reagents followed by removal of the nitrogen protecting group provides enantiomerically pure α-amino aryl ketones as their corresponding HCl salts. This practical two-step sequence gives rapid access to a pharmaceutically interesting class of compounds from commercially available starting materials.

Key words

arylations - amino acids - lithiation - ketones - nucleophilic additions

    References

  • 1 Sheppard GS. Florjancic AS. Giesler JR. Xu L. Guo Y. Davidsen SK. Marcotte PA. Elmore I. Albert DH. Magoc TJ. Bouska JJ. Goodfellow CL. Morgan DW. Summers JB. Bioorg. Med. Chem. Lett.  1998,  8:  3251 
    CrossrefGoogle Scholar
  • 2a Maurer PJ. Knudsen CG. Palkowicz AD. Rapoport H. J. Org. Chem.  1985,  50:  325 
    Google Scholar
  • 2b Cupps TL. Boutin RH. Rapoport H. J.Org.Chem.  1985,  50:  3972 
    Google Scholar
  • 2c Knudsen CG. Rapoport H. J. Org. Chem.  1983,  48:  2260 
    Google Scholar
  • 2d Buckley TF. Rapoport H. J. Am. Chem. Soc.  1981,  103:  6157 
    Google Scholar
  • 2e Luca L. Giamcomelli G. Porcheddu A. Org.Lett.  2001,  3:  1519 
    Google Scholar
  • 3a Klix RC. Chamberlin SA. Bhatia AV. Debroah DA. Hayes TK. Rojas FG. Koops RW. Tetrahedron Lett.  1995,  36:  1791 
    CrossrefGoogle Scholar
  • 3b Takahashi Y. Ishiwata H. Deushi T. Nakayama M. Shiratsuchi M. Tetrahedron Lett.  1991,  32:  1067 
    CrossrefGoogle Scholar
  • 4 McClure DE. Arison BH. Jones JH. Baldwin JJ. J. Org. Chem.  1981,  46:  2431 
    Google Scholar
  • 5 Paleo MR. Sardina FJ. Tetrahedron Lett.  1996,  37:  3403 
    CrossrefGoogle Scholar
  • 6 Sengupta S. Mondal S. Das D. Tetrahedron Lett.  1999,  40:  4107 
    Google Scholar
  • 7a Bonini BF. Franchini-Comes M. Fochi M. Mazzanti G. Ricci A. Varchi G. Synlett  1998,  1013 
    CrossrefGoogle Scholar
  • 7b Giordano A. Monica C. Landi F. Spinella A. Sodano G. Tetrahedron Lett.  2000,  41:  3979 
    CrossrefGoogle Scholar
  • 8 Mattson MN. Rapoport H. J. Org. Chem.  1996,  61:  6071 
    Google Scholar
  • 9 Berree F. Chang K. Cobas A. Rapoport H. J. Org. Chem.  1996,  61:  715 
    Google Scholar
  • 10 Nahm S. Weinreb SM. Tetrahedron Lett.  1981,  22:  3815 
    CrossrefGoogle Scholar
  • 11 Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   Wiley; New York: 1991. 
    Google Scholar
  • 12 Pace RD. Kabalka GW. J. Org. Chem.  1995,  60:  4838 
    Google Scholar
13

Florjancic, A.; Curtin, M., unpublished results.

14

HPLC analysis with ChiralPak AD 4.6 × 250 mm column from Chiral Technologies. Solvent system: 25-40% EtOH in hexanes.