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.

Synthesis of γ-nitroaldehydes containing quaternary carbon in the α-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst

“…23 As mentioned, catalytic mechanism of 4-OT in Michael addition relies on promiscuous activity of this enzyme and terminal proline residue that participates in the formation of a nucleophilic enamine intermediate. 15,[39][40][41][42] In most cases product yields reported were between 31-51% which is comparable to our biocatalytic result but reaction times were about 3-5 times longer (70-96 h vs. 20 h). 1-(2-Nitro-1-phenylethyl)cyclohexanecarbaldehyde (1c) was previously obtained by organocatalysis.…”

Synthesis, anticholinesterase and antioxidant potentials of ketoesters derivatives of succinimides: a possible role in the management of Alzheimer’s

“…Organocatalysis is an emerging field in practice over the past decade [ 24 ]. Over this time different organocatalysts have been explored for various organic reactions [ 25 ]. Michael addition is one of the important reactions targeted by several researchers for testing potent organocatalysts [ 26 ].…”

<p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>

“…This is also obvious from previous reported studies that asymmetric nitrogenous molecules are important building blocks of medicinal importance and may possesses diverse pharmacological potential. [37][38][39][40] Based on the importance of succinimide scaffold and the dire need of the novel drugs, the current study has been designed in an attempt to synthesize potential derivatives of succinimide and to evaluate them for various biological activities including the anti-Alzheimer's and anti-diabetic using in-vitro and in-silico simulation approaches. , and α-glucosidase from Saccharomyces cerevisiae (CAT No.…”