title: Chiral picolylamines for Michael and aldol reactions: probing substrate boundaries.
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.
authors.affiliation: Department of Chemistry, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany. t.nugent@jacobs-university.de
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Nugent
authors.forename: Ahtaram
authors.initials: A
authors.lastname: Bibi
authors.forename: Abdul
authors.initials: A
authors.lastname: Sadiq
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shoaib
authors.forename: M Naveed
authors.initials: MN
authors.lastname: Umar
authors.forename: Foad N
authors.initials: FN
authors.lastname: Tehrani
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003512:Cyclohexanones / Q000737:chemistry*; D003517:Cyclopentanes / Q000737:chemistry; D003959:Diamines / Q000737:chemistry*; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013343:Styrenes / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D003512:Cyclohexanones; D003517:Cyclopentanes; D003959:Diamines; D011725:Pyridines; D013343:Styrenes; C007201:cyclopentanone; C011955:beta-nitrostyrene; C036468:cyclohexanone; C116609:3-hydroxybutanal; C017439:isobutyraldehyde