Synlett 2010(3): 503-504  
DOI: 10.1055/s-0029-1219339
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

2-Methyl-2-propanesulfinamide (Ellman’s Sulfinamide): A Versatile Chiral Reagent

Xiao-Yu Guan*
Chengdu Institute of Organic Chemistry, Chinese Academy of ­Sciences, Chengdu, P. R. of China
e-Mail: guanxy04@mails.gucas.ac.cn;
Further Information

Publication History

Publication Date:
25 January 2010 (online)

Introduction

Enantiopure 2-methyl-2-propanesulfinamide (tert-butane­sulfinamide) was introduced by Ellman in 1997. [¹] As a chiral ammonia equivalent, it can easily condense with aldehydes and ketones to afford tert-butanesulfinyl imines in high yields (Scheme 1). [²] The tert-butanesulfinyl group activates these imines for the addition of many different classes of nucleophiles and serves as a powerful chiral ­directing group to provide products with generally high diastereoselectivity. Subsequent removal of the tert-butanesulfinyl group under mild conditions cleanly provides the amine products. Many versatile building blocks [³] including syn- and anti-1,2- or 1,3-amino alcohols, [4] [5] α-branched and α,α-dibranched amines, [6] α- or β-amino acids and esters [7] [8] can be efficiently synthesized by using this methodology. In addition, this methodology can also be used in the synthesis of antibiotics, biologically active compounds, and other complex natural products. [9] Furthermore, tert-butanesulfinamide has been used in the synthesis of asymmetric ligands [¹0] or catalysts [¹¹] , and in a few cases, appears as the chirality-bearing component. [¹²]

Scheme 1 Synthesis of sulfinyl aldimines or ketimines

Each configuration of 2-methyl-2-propanesulfinamid is readily available in a two-step process of catalytic asymmetric oxidation of tert-butyl disulfide, followed by the reaction of the tert-butanethiosulfinate product 4 with an amide anion (Scheme 2). [¹³]

Scheme 2 Preparation of (R)-tert-butanesulfinamide

    References

  • 1 Liu G. Cogan DA. Ellman JA. J. Am. Soc. Chem.  1997,  119:  9913 
  • 2 Liu G. Cogan DA. Owens TD. Tang TP. Ellman JA. J. Org. Chem.  1999,  64:  1278 
  • 3For a recent review, see:
  • 3 Ellman JA. Owens TD. Tang TP. Acc. Chem. Res.  2002,  35:  984 
  • 1,2-amino alcohols:
  • 4a Zhong Y.-W. Dong Y.-Z. Fang K. Izumi K. Xu M.-H. Lin G.-Q. J. Am. Chem. Soc.  2005,  127:  11956 
  • 4b Evans JW. Ellman JA. J. Org. Chem.  2003,  68:  9948 
  • 4c Tang TP. Volkman SK. Ellman JA. J. Org. Chem.  2001,  66:  3707 
  • 4d Huang H.-X. Guo X. Hu W.-H. Angew. Chem. Int. Ed.  2007,  46:  1337 
  • 1,3-amino alcohols:
  • 5a Kochi T. Tang TP. Ellman JA. J. Am. Chem. Soc.  2003,  125:  11276 
  • 5b Kochi T. Tang TP. Ellman JA. J. Am. Chem. Soc.  2002,  124:  6518 
  • 6a Cogan DA. Liu G. Ellman JA. Tetrahedron  1999,  55:  8883 
  • 6b Cogan DA. Ellman JA. J. Am. Chem. Soc.  1999,  121:  268 
  • 6c   , 
  • α-amino acids:
  • 7a Avenoza A. Busto JH. Corzana F. Peregrina JM. Sucunza D. Zurbano MM. Synthesis  2005,  575 
  • 7b Naskar D. Roy A. Seibel WL. Portlock DE. Tetrahedron Lett.  2003,  44:  8865 
  • β-amino acids and esters:
  • 8a Jacobsen MF. Skrydstrup T. J. Org. Chem.  2003,  68:  7122 
  • 8b Tang TP. Ellman JA. J. Org. Chem.  2002,  67:  7819 
  • 8c Tang TP. Ellman JA. J. Org. Chem.  1999,  64:  12 
  • Some recent examples:
  • 9a Lu BZ. Senanayake C. Li N. Han Z. Bakale R. P . Wald SA. Org. Lett.  2005,  7:  2599 
  • 9b Kochi T. Ellman JA. J. Am. Chem. Soc.  2004,  126:  15652 
  • 9c Higashibayashi S. Kohno M. Goto T. Suzuki K. Mori T. Hashimoto K. Nakata M. Tetrahedron Lett.  2004,  45:  3707 
  • 10a Kato T. Marubayashi K. Takizawa S. Sasai H. Tetrahedron: Asymmetry  2004,  15:  3693 
  • 10b Owens TD. Hollander FJ. Oliver AG. Ellman JA. J. Am. Chem. Soc.  2001,  123:  1539 
  • 11 Robak MT. Trincado M. Ellman JA. J. Am. Chem. Soc.  2007,  129:  15110 
  • 12a Schenkel LB. Ellman JA. J. Org. Chem.  2004,  69:  1800 
  • 12b Schenkel LB. Ellman JA. Org. Lett.  2003,  5:  545 
  • 12c Owens TD. Souers AJ. Ellman JA. J. Org. Chem.  2003,  68: 
  • 13 Weix DJ. Ellman JA. Wang X. Curran DP. Org. Synth.  2005,  82:  157 
  • 14 Beenen MA. An C. Ellman JA. J. Am. Chem. Soc.  2008,  130:  6910 
  • 15a Morton D. Pearson D. Field RA. Stockman RA. Synlett  2003,  1985 
  • 15b Chemla F. Ferreira F. J. Org. Chem.  2004,  69:  8244