Synthesis 2007(10): 1587-1588  
DOI: 10.1055/s-2007-965953
PSP
© Georg Thieme Verlag Stuttgart · New York

Practical Aspects in the Gram-Scale Synthesis of Chiral Diamino-Bithiophene ‘DAT2’ Ligand

Marco Bandini, Astrid Eichholzer, Simona Tommasi, Achille Umani-Ronchi*
Dipartimento di Chimica ‘G. Ciamician’, Università di Bologna, via Selmi 2, 40126 Bologna, Italy
Fax: +39(051)2099456; e-Mail: [email protected];
Further Information

Publication History

Received 24 January 2007
Publication Date:
28 February 2007 (online)

Abstract

A gram-scale synthesis of the enantiomerically pure ligand DAT2 is described. The mild reaction conditions, operational simplicity, and satisfying isolated yield (68%) are some of the main features of this two-step reductive amination.

    References and Notes

  • 1a Comprehensive Asymmetric Catalysis   Jacobsen NE. Pfaltz A. Yamamoto H. Springer; Berlin: 1999. 
  • 1b Ojima I. In Catalytic Asymmetric Synthesis   Vol. II:  Wiley-VCH; New York: 2000. 
  • 2 Farina V. Reeves JT. Senanayake CH. Song JJ. Chem. Rev.  2006,  106:  2734 
  • 3 Yoon TP. Jacobsen EN. Science  2003,  299:  1691 
  • 4a Kim S.-H. Lee E.-K. Kim G.-J. Bull. Korean Chem. Soc.  2004,  25:  754 
  • 4b Albano VG. Bandini M. Melucci M. Monari M. Piccinelli F. Tommasi S. Umani-Ronchi A. Adv. Synth. Catal.  2005,  347:  1507 
  • 4c Albano VG. Bandini M. Barbarella G. Melucci M. Monari M. Piccinelli F. Tommasi S. Umani-Ronchi A. Chem. Eur. J.  2006,  12:  667 
  • 5 Bandini M. Piccinelli F. Tommasi S. Umani-Ronchi A. Ventrici C. Chem. Commun.  2007,  616 
  • 7a Bandini M. Benaglia M. Quinto T. Tommasi S. Umani-Ronchi A. Adv. Synth. Catal.  2006,  348:  1521 
  • 7b

    Bandini M., Benaglia M., Tommasi S., Umani-Ronchi A., unpublished results.

  • 8 Melucci M. Barbarella G. Gazzano M. Cavallini M. Biscarini F. Bongini A. Piccinelli F. Monari M. Bandini M. Umani-Ronchi A. Biscarini P. Chem. Eur. J.  2006,  12:  7305 
  • 9 Enantiomerically pure (1R,2R)-cyclohexane-1,2-diamine was purchased from Aldrich and Co. (1 g, 38.40 e) but can be conveniently prepared as both enantiomers (multigram scale) following a known procedure: Schanz H.-J. Linseis MA. Gilheany DG. Tetrahedron: Asymmetry  2003,  14:  2763 
6

Bandini M., Tommasi S., Umani-Ronchi A., unpublished results.

10

When 1 was prepared on a large scale, the addition of an excess of cyclohexane-1,2-diamine during the reaction course was necessary in order to guarantee complete conversion.

11

The crude bis-imine intermediate was poorly soluble in MeOH and relatively large amounts of solvent were usually required for the reductive process.

12

Note, cooling the reaction to 0 °C during quenching would prevent the rapid evolution of gas.