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Synlett 2003(3): 0365-0368
DOI: 10.1055/s-2003-37105
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantiopure Guanidine Bases For Enantioselective Enone Epoxidations: 1, Acyclic Guanidines

Julie C. McManusa, John S. Careyb, Richard J. K. Taylor*a
a Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Fax: +44(1904)434523; e-Mail: rjkt1@york.ac.uk;
b GlaxoSmithKline Pharmaceuticals, Leigh, Tonbridge, Kent TN11 9AN, UK
Further Information

Publication History

Received 20 December 2002
Publication Date:
07 February 2003 (online)

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Abstract

A range of structurally and functionally varied enantiopure guanidines has been prepared and evaluated in the enantioselective epoxidation of 3-tert-butoxycarbonylamino-4,4-dimethoxycyclohexa-2,5-dien-1-one 1 using tert-butylhydroperoxide. Successful enantioselective epoxidations were observed and useful structure-activity data obtained, but the reactions were slow and the maximum ee observed was 30%.

Key words

enantioselective - epoxidation - enones - guanidines - stereoselectivity

    References

  • For reviews on epoxy ketones as versatile building blocks see:
  • 1a Lauret C. Tetrahedron: Asymmetry  2001,  12:  2359 
    CrossrefGoogle Scholar
  • 1b Bonini C. Righi G. Tetrahedron  2002,  58:  4981 
    CrossrefGoogle Scholar
  • 2 For a review see: Porter MJ. Skidmore J. Chem. Commun.  2000,  1215 
    CrossrefGoogle Scholar
  • 3a Gautier ECL. Lewis NJ. McKillop A. Taylor RJK. Tetrahedron Lett.  1994,  35:  8759 
    CrossrefGoogle Scholar
  • 3b McKillop A. McLaren L. Taylor RJK. Watson RJ. Lewis N. J. Chem. Soc., Perkin Trans. 1  1996,  1385 
    CrossrefGoogle Scholar
  • 3c Graham AE. McKerrecher D. Davies DH. Taylor RJK. Tetrahedron Lett.  1996,  37:  7445 
    CrossrefGoogle Scholar
  • 3d Graham AE. Taylor RJK. J. Chem. Soc., Perkin Trans. 1  1997,  1087 
    CrossrefGoogle Scholar
  • 3e Ragot JP. Steeneck C. Alcaraz M.-L. Taylor RJK. J. Chem. Soc., Perkin Trans. 1  1999,  1073 
    CrossrefGoogle Scholar
  • 3f Runcie KA. Taylor RJK. Org. Lett.  2001,  3:  3237 
    CrossrefGoogle Scholar
  • 4a Alcaraz L. Macdonald G. Ragot J. Lewis NJ. Taylor RJK. Tetrahedron  1999,  55:  3707 
    Google Scholar
  • 4b Alcaraz L. Macdonald G. Ragot J. Lewis NJ. Taylor RJK. J. Org. Chem.  1998,  63:  3526 
    Google Scholar
  • 4c Taylor RJK. Alcaraz L. Kapfer-Eyer I. Macdonald G. Wei X. Lewis NJ. Synthesis  1997,  775 ; and references therein
    Google Scholar
  • 5 Macdonald G. Alcaraz L. Lewis NJ. Taylor RJK. Tetrahedron Lett.  1998,  39:  5433 
    CrossrefGoogle Scholar
  • 6 Dwyer CL. Gill CD. Ichihara O. Taylor RJK. Synlett  2000,  704 
    Article in Thieme ConnectGoogle Scholar
  • 7a Genski T. Macdonald G. Wei X. Lewis N. Taylor RJK. Synlett  1999,  795 
    Google Scholar
  • 7b Genski T. Macdonald G. Wei X. Lewis N. Taylor RJK. Arkivoc  2000,  1:  266 
    Google Scholar
  • For recent reviews see:
  • 8a Ishikawa T. Isobe T. Chem. Eur. J.  2002,  8:  553 
    CrossrefPubMedGoogle Scholar
  • 8b Schmidtchen FP. Berger M. Chem. Rev.  1997,  97:  1609 ; and references therein
    CrossrefPubMedGoogle Scholar
  • For recent publications in the area of enantiopure guanidines see: Michael Additions:
  • 9a Ishikawa T. Araki Y. Kumamoto T. Seki H. Fukuda K. Isobe T. Chem. Commun.  2001,  245 ; and references therein
    CrossrefGoogle Scholar
  • 9b Howard-Jones A. Murphy PJ. Thomas DA. Caulkett PWR. J. Org. Chem.  1999,  64:  1039 
    CrossrefGoogle Scholar
  • 9c Ma K. Cheng K. Tetrahedron: Asymmetry  1999,  10:  713 
    CrossrefGoogle Scholar
  • 10a Strecker Synthesis: Corey EJ. Grogan MJ. Org. Lett.  1999,  1:  157 
    CrossrefGoogle Scholar
  • 10b Henry Reaction: Chinchilla R. Nájera C. Sánchez-Agulló P. Tetrahedron: Asymmetry  1994,  5:  1393 
    CrossrefGoogle Scholar
  • 11 Yamamoto Y. Kojima S. In The Chemistry of Amidines and Imidates   Vol. 2:  Patai S. Rappoport Z. Wiley; New York: 1991. 
    Google Scholar
  • 12a Kim KS. Qian L. Tetrahedron Lett.  1993,  34:  7677 
    CrossrefGoogle Scholar
  • 12b Levallet C. Lerpiniere J. Ko SY. Tetrahedron  1997,  53:  5291 
    CrossrefGoogle Scholar
  • 14a Baker TJ. Tomioka M. Goodman M. Org. Synth.  2000,  78:  91 
    CrossrefGoogle Scholar
  • 14b Zapf CW. Creighton CJ. Tomioka M. Goodman M. Org. Lett.  2001,  3:  1133 ; and references therein
    CrossrefGoogle Scholar
  • Preparation of 8d·HCl salt:
  • 15a

    (S)-1-Methoxy-2-propyl-amine (2.59 g, 29.1 mmol) was added to a solution of N,N′-di-Boc-N′′-trifluoromethanesulfonylguanidine 6 (7.59 g, 19.4 mmol) and diisopropyl(ethyl)amine (5.1 cm3, 29.3 mmol) in CH2Cl2, under argon. The reaction was at r.t. for 2 h before the solvent was removed under reduced pressure and the residue was purified by flash silica chromatography (CH2Cl2) to give N,N′-di-Boc-N′′-[(1S)-2-methoxy-1-methylethyl]guanidine 7d (6.12 g, 95%) as a white solid, mp 79-80 °C; [α]D 20 -6.5 (c 1.0, CHCl3) which was fully characterised.

    Google Scholar
  • 15b

    The Boc-protected guanidine 7d (6.05 g, 18.2 mmol) was dissolved in approx. 3 M anhyd methanolic HCl (100 cm3) and was stirred at 40 °C, under argon, for 18 h. The solvent was then removed under reduced pressure to afford N′′-[(1S)-2-methoxy-1-methylethyl]guanidine hydrochloride (8d·HCl) quantitatively (3.03 g) as a hygroscopic gum, [α]D 20 -24.3 (c 1.00, MeOH). IR (neat): νmax: 3253 and 3147 (NH), 2981 and 2934 (CH), 1640 (CN3) cm-1. 1H NMR (400 MHz, CD3OD): δ = 3.84-3.79 (1 H, m, CH), 3.47 (1 H, dd, J = 9.5 and 4.0, CHAHBOMe), 3.40 (3 H, s, OCH3), 3.37 (1 H, dd, J = 9.5 and 6.5, CHAHBOMe), 1.23 (3 H, d, J = 6.5, CH3). 13C NMR (100 MHz, CD3OD): δC = 158.3 (CN3), 76.9 (CH), 59.4 (OCH3), 48.5 (CH2), 17.4 (CH3). MS (CI): m/z = 132(100) [MH+]; HRMS (CI): Calcd for C5H14N3O: 132.1137. Found: [MH+]: 132.1132 (2.7 ppm error).

    Google Scholar
  • 16 The C2-symmetric pyrrolidines were prepared according to: Yamamoto Y. Hoshino J. Fujimoto Y. Ohmoto J. Sawada S. Synthesis  1993,  298 
    Article in Thieme ConnectGoogle Scholar
  • 17 Guo Z.-X. Cammidge AN. Horwell DC. Synth. Commun.  2000,  30:  2933 ; and references therein
    CrossrefGoogle Scholar
13

All new compounds were fully characterised by 1H NMR, 13C NMR and IR spectroscopies plus HRMS or elemental analysis.

18

Chiral HPLC was carried out using a Chiralcel OJ column (25 cm × 4.6 mm) with hexane-isopropanol (98:2) as eluent at a flow rate of 1 mL/min and detection at 276 nm.