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.

asymmetric catalysis - chiral ligands - amine - thiophene

References and Notes

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Bandini M., Benaglia M., Tommasi S., Umani-Ronchi A., unpublished results.

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<A NAME="RZ02407SS-9">9</A> 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 

<A NAME="RZ02407SS-10">10</A>

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.

<A NAME="RZ02407SS-11">11</A>

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

<A NAME="RZ02407SS-12">12</A>

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