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

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.

Key words

asymmetric catalysis - chiral ligands - amine - thiophene

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  Bandini M., Benaglia M., Tommasi S., Umani-Ronchi A., unpublished results.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Bandini M., Tommasi S., Umani-Ronchi A., unpublished results.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