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 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
6 Bandini M., Tommasi S., Umani-Ronchi A., unpublished results.
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7b Bandini M., Benaglia M., Tommasi S., Umani-Ronchi A., unpublished results.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 R ,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
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.
