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Synlett 2011(4): 464-468  
DOI: 10.1055/s-0030-1259528
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© Georg Thieme Verlag Stuttgart ˙ New York

Catalytic Batch and Continuous Flow Production of Highly Enantioenriched Cyclohexane Derivatives with Polymer-Supported Diarylprolinol Silyl Ethers

Esther Alzaa, Sonia Sayaleroa, Xacobe C. Cambeiroa, Rafael Martín-Rapúna, Pedro O. Mirandaa, Miquel A. Pericàs*a,b
a Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain
b Departament de Química Orgànica, Universitat de Barcelona (UB), 08028 Barcelona, Spain
Fax: +34(977)920222; e-Mail: mapericas@iciq.es;
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Publication History

Received 15 December 2010
Publication Date:
02 February 2011 (online)

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Abstract

Diarylprolinol silyl ethers immobilized onto polystyrene have been employed as catalysts in the enantioselective domino Michael-Knoevenagel reaction of dimethyl 3-oxoglutarate and 3-substituted acrolein derivatives, including aliphatic ones. The best catalyst allows the preparation of highly functionalized cyclohexane derivatives in a straightforward and efficient manner, both under batch and continuous flow conditions.

Key words

asymmetric organocatalysis - domino process - Michael addition - Knoevenagel condensation - flow reactors

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15

See Supporting Information for details.

16

General Procedure for the Domino Michael-Knoevenagel Process of α,β-Unsaturated Aldehydes and Dimethyl 3-Oxopentanedioate: Benzoic acid (0.05 mmol), the corresponding aldehyde (0.25 mmol) and dimethyl 3-oxopentanedioate (0.275 mmol) were added to catalyst 5 (0.025 mmol) previously swollen in CH2Cl2 (1 mL). The suspension was shaken at r.t. for the time indicated in Table  [²] and then directly filtered. The resin was rinsed with CH2Cl2 (3 × 1 mL) and the organic filtrate was concentrated under reduced pressure. MeOH (1 mL) and NaBH4 (0.25 mmol) were added to a solution of the resulting crude in CH2Cl2 (0.5 mL) at 0 ˚C, which was stirred at that temper-ature for 20 min. After addition of the pH 7 phosphate buffer, the organic materials were extracted with CH2Cl2 and the combined organic phase was dried over Na2SO4, and then concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (CH2Cl2-EtO2) to afford 7.

17

The deposition number at the Cambridge Crystallographyc Data Centre is CCDC 804763.

18

These recycling experiments show the results obtained in six consecutive runs. After each run, the reaction mixture was filtered and the solid-supported catalyst was washed with CH2Cl2 and directly reused.