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Synlett 2011(2): 177-180  
DOI: 10.1055/s-0030-1259282
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

New Potentially Chelating Chiral Magnesium Amide Bases for Use in Enantioselective Deprotonation Reactions

William J. Kerr*, Michael Middleditch, Allan J. B. Watson
Department of Pure and Applied Chemistry, WestCHEM, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK
Fax: +44(141)5484246; e-Mail: w.kerr@strath.ac.uk;
Further Information

Publication History

Received 12 November 2010
Publication Date:
23 December 2010 (online)

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Abstract

A series of chiral secondary amines, incorporating a five- or six-membered heterocycle, were synthesised and used to prepare novel chiral magnesium bisamide reagents. These amide bases were subsequently applied within asymmetric deprotonation reactions to probe the potential for chelation-assisted selectivity enhancement. Good levels of selectivity could be achieved [up to 87:13 er (R/S)] across a range of prochiral cyclohexanone substrates when employing a thiophene-derived magnesium bisamide complex.

Key words

asymmetric synthesis - enantioselectivity - heterocycles - enolate - magnesium

    References and Notes

  • 1 For a review on the use of magnesium amide reagents, see: Henderson KW. Kerr WJ. Chem. Eur. J.  2001,  7:  3430 
    CrossrefSearch in Google Scholar
  • 2a Henderson KW. Kerr WJ. Moir JH. Chem. Commun.  2000,  479 
  • 2b Henderson KW. Kerr WJ. Moir JH. Synlett  2001,  1253 
  • 2c Henderson KW. Kerr WJ. Moir JH. Chem. Commun.  2001,  1722 
  • 2d Anderson JD. García García P. Hayes D. Henderson KW. Kerr WJ. Moir JH. Fondekar KP. Tetrahedron Lett.  2001,  42:  7111 
    Search in Google Scholar
  • 2e Henderson KW. Kerr WJ. Moir JH. Tetrahedron  2002,  58:  4573 
    Search in Google Scholar
  • 2f Carswell EL. Hayes D. Henderson KW. Kerr WJ. Russell CJ. Synlett  2003,  1017 
  • 2g Bassindale MJ. Crawford JJ. Henderson KW. Kerr WJ. Tetrahedron Lett.  2004,  45:  4175 
    Search in Google Scholar
  • 4 Cain CM. Cousins RPC. Coumbarides G. Simpkins NS. Tetrahedron  1990,  46:  523 
    CrossrefSearch in Google Scholar
  • 6 Brunner H. Reiter B. Reipl G. Chem. Ber.  1984,  117:  1330 
    CrossrefSearch in Google Scholar
  • 8a Zylber J. Tubul A. Brun P. Tetrahedron: Asymmetry  1995,  6:  377 
    Search in Google Scholar
  • 8b Rogatchov VO. Bernsmann H. Schwab P. Froehlich R. Wibbeling B. Metz P. Tetrahedron Lett.  2002,  43:  4753 
    Search in Google Scholar
  • 9 For amine acylation with α-amino esters, see: Juaristi E. Beck AK. Hansen J. Matt T. Mukhopadhyay T. Simson M. Seebach D. Synthesis  1993,  1271 
    Thieme Connect
  • 11 Thiophene is commonly used as a phenyl isostere within medicinal chemistry; for example, see: Silverman RB. The Organic Chemistry of Drug Design and Drug Action   2nd ed.:  Academic Press; New York: 2004.  p.32 
    Search in Google Scholar
  • The absolute solution-state structure of (R)-3 is currently unknown and efforts to crystallise this complex have so far been unsuccessful. However, the structure of the related achiral bisamide complex derived from dibenzylamine is known, see:
  • 12a Clegg W. Craig FJ. Henderson KW. Kennedy AR. Mulvey RE. O’Neil PA. Reed D. Inorg. Chem.  1997,  36:  6238 
    Search in Google Scholar
  • 12b Conway B. Hevia E. Kennedy AR. Mulvey RE. Weatherstone S. Dalton Trans.  2005,  1532 
  • 12c Andrikopoulos PC. Armstrong DR. Kennedy AR. Mulvey RE. O’Hara CT. Rowlings RB. Weatherstone S. Inorg. Chim. Acta  2007,  360:  1370 
    Search in Google Scholar
3

Commercially available from Aldrich Chemical Co., CAS# [38235-77-7], catalogue no. 431737.

5

Commercially available from BASF SE (ChiPros®) (http://www.intermediates.basf.com/en/intermed/products/chipros/amines/) or the Aldrich Chemical Co.: (R)-1-phenylethyl-amine CAS# [3886-69-9]; and (S)-1-phenylethylamine CAS# [2627-86-3].

7

Due to limited availability of (R)-phenylethylamine during the course of this study, we were compelled to use the more readily obtainable S-enantiomer for the preparation of several of the desired chiral amines.

10

Commercially available from Aldrich Chemical Co., CAS# [1191-47-5].