Subscribe to RSS
Practical Aspects in the Gram-Scale Synthesis of Chiral Diamino-Bithiophene ‘DAT2’ Ligand
28 February 2007 (online)
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
Comprehensive Asymmetric Catalysis
JacobsenNE. PfaltzA. YamamotoH. Springer; Berlin: 1999.
OjimaI. In Catalytic Asymmetric Synthesis Vol. II: Wiley-VCH; New York: 2000.
FarinaV. ReevesJT. SenanayakeCH. SongJJ. Chem. Rev. 2006, 106: 2734
YoonTP. JacobsenEN. Science 2003, 299: 1691
KimS.-H. LeeE.-K. KimG.-J. Bull. Korean Chem. Soc. 2004, 25: 754
AlbanoVG. BandiniM. MelucciM. MonariM. PiccinelliF. TommasiS. Umani-RonchiA. Adv. Synth. Catal. 2005, 347: 1507
AlbanoVG. BandiniM. BarbarellaG. MelucciM. MonariM. PiccinelliF. TommasiS. Umani-RonchiA. Chem. Eur. J. 2006, 12: 667
BandiniM. PiccinelliF. TommasiS. Umani-RonchiA. VentriciC. Chem. Commun. 2007, 616
BandiniM. BenagliaM. QuintoT. TommasiS. Umani-RonchiA. Adv. Synth. Catal. 2006, 348: 1521
Bandini M., Benaglia M., Tommasi S., Umani-Ronchi A., unpublished results.
MelucciM. BarbarellaG. GazzanoM. CavalliniM. BiscariniF. BonginiA. PiccinelliF. MonariM. BandiniM. Umani-RonchiA. BiscariniP. 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:
SchanzH.-J. LinseisMA. GilheanyDG. Tetrahedron: Asymmetry 2003, 14: 2763
References and Notes
Bandini M., Tommasi S., Umani-Ronchi A., unpublished results.10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.