Organic & Biomolecular Chemistry 2012-12-14

Chiral picolylamines for Michael and aldol reactions: probing substrate boundaries.

Thomas C Nugent, Ahtaram Bibi, Abdul Sadiq, Mohammad Shoaib, M Naveed Umar, Foad N Tehrani

Index: Org. Biomol. Chem. 10(46) , 9287-94, (2012)

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Abstract

Here we report on inroads concerning increased substrate breadth via the picolylamine organocatalyst template, a vicinal chiral diamine based on a pyridine-primary amine motif. The addition of cyclohexanone to β-nitrostyrene has many catalyst solutions, but cyclopentanone and isobutyraldehyde additions continue to be challenging. PicAm-3 (10 mol%) readily allows the Michael addition of cyclopentanone or isobutyraldehyde (5.0 equiv.) to β-nitrostyrene derivatives. By contrast, PicAm-1 (7.0 mol%) is optimal for catalyzing the aldol reaction of cyclohexanone or cycloheptanone (3.3 equiv.) with aromatic aldehydes. Eighteen products are reported and for each reaction type new products are reported (4b-d, 9c). Very good yields and stereoselectivities are generally noted. The reactions, which require an acid additive, proceed via a transient chiral enamine and a mechanistic case is put forth for a bifunctional catalysis model.