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Synlett 2005(15): 2321-2324  
DOI: 10.1055/s-2005-872672
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient and General One-Pot Method for the Synthesis of Chiral Bis(oxazoline) and Pyridine Bis(oxazoline) Ligands

A. Cornejob, J. M. Frailea, J. I. García*a, M. J. Gilb, V. Martínez-Merinob, J. A. Mayorala, E. Pires*a, I. Villalbaa
a Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Ciencia de Materiales de Aragón and Instituto Universitario de Catálisis Homogénea, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
Fax: +34(976)762077; e-Mail: jig@unizar.es;
b Departamento de Química Aplicada, Universidad Pública de Navarra, 31006 Pamplona, Spain
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Publication History

Received 19 May 2005
Publication Date:
07 September 2005 (online)

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Abstract

An expeditious method for the synthesis of chiral box and pybox ligands is reported. The approach is based on a one-pot condensation reaction of chiral β-amino alcohols with a dinitrile ­using stoichiometric or catalytic amounts of zinc triflate. Yields greater than 90% are obtained in many cases without the need for further purification of the product.

Key words

bis(oxazolines) - pybox - synthesis - zinc triflate - toluene - chiral ligands

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The 1H NMR signals of the box-ZnCl2 complex were observed.

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General Procedure for the Preparation of Box.
A 100-mL two-necked round-bottomed flask fitted with a reflux condenser was charged with 2,2-dimethyl malononitrile (564 mg, 6 mmol) and zinc triflate (2, 177.4 mg, 6 mmol). The system was purged with argon and anhyd toluene (40 mL) was added. The solution was stirred during 5 min and a solution of the β-amino alcohol (12 mmol) in anhyd toluene (20 mL) was added. The solution was heated under reflux for 48 h [72 h when tert-leucinol and (S)-2-methylphenylglycinol were used]. The system was allowed to cool. The reaction was then washed with brine (3 × 75 mL) and NaHCO3 (3 × 70 mL), dried with MgSO4 and the solvent evaporated to give pure product.

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(S)-2-Methylphenylglycinol: 1H NMR (400 MHz, CDCl3): δ = 1.42 (s, 3 H), 2.06 (br s, 3 H), 3.59 (dd, 2 H, J 1 = 10.68 Hz, J 2 = 13.11 Hz), 7.19 (t, 1 H, J = 6.57 Hz), 7.35 (dd, 2 H, J = 6.57 Hz, J = 8.08 Hz), 7.45 (d, 2 H, J = 8.08 Hz). 13C NMR (100 MHz, CDCl3): δ = 27.09, 56.38, 71.71, 125.29, 126.85, 128.49, 146.31. [α]D 25 10.97 (c 0.75, HCl 1 N). Anal. Calcd for C9H13NO: C, 71.49; H, 8.67; N, 9.26. Found: C, 71.40; H, 8.65; N, 9.31.

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1H NMR and [α]D data for box and pybox ligands bearing phenyl, benzyl, isopropyl, tert-butyl or indanyl groups were compared with those described in the literature. [7] [9] [13a] [22-24] Purity of those products was verified by elemental analysis.

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General Procedure for the Preparation of Pybox.
A 100-mL two-necked round-bottomed flask fitted with a reflux condenser was charged pyridine-2,6-dicarbonitrile (774 mg, 6 mmol) and the adequate amount of zinc triflate (5% mol for 3a and 3d and 10% mol for 3b and 3c). The system was purged with argon and anhyd toluene (40 mL) was added. The solution was stirred during 5 min and a solution of the β-amino alcohol (12 mmol) in anhyd toluene (20 mL) was added. The solution was heated under reflux for 48 h. The system was allowed to cool, and reaction was diluted with 50 mL of EtOAc. The solution was then washed with brine (3 × 75 mL) and NaHCO3 (3 × 70 mL), dried with MgSO4 and the solvent evaporated to give pure product.