Fluoride Additive as a Simple Tool to Qualitatively Improve Performance of Nickel-Catalyzed Asymmetric Michael Addition of Malonates to Nitroolefins.

Nowadays, design of the new chiral ligands for organometallic catalysts is often based on the step-by-step increase in their complexity to improve efficiency. Herein we describe that simple in situ addition of the fluoride source to the asymmetric organometallic catalyst can improve not only activity but also enantioselectivity. Bromide-nickel diimine complexes were found to catalyze asymmetric Michael addition in low yields and ee, but activation with fluoride leads to a significant improvement in catalyst performance. The developed approach was applied to prepare several enantioenriched GABA analogues.

Redox Condensations of o-Nitrobenzaldehydes with Amines under Mild Conditions: Total Synthesis of the Vasicinone Family.

A total synthesis of the vasicinone family of natural products from bulk chemicals was developed. Reductive condensation of o-nitrobenzaldehydes with amines utilizing iron pentacarbonyl as a reducing agent followed by subsequent oxidation leads to a great variety of polycyclic nitrogen-containing heterocycles under mild conditions. Enantiomerically pure vasicinone, rutaecarpine, isaindigotone, and luotonin were synthesized from readily available starting materials like hydroxyproline, nitrobenzaldehyde, pyrrolidine, and piperidine in two to four operational steps without chromatography. The antifungal activity of all products was tested.

Sodium Hypophosphite as a Bulk and Environmentally Friendly Reducing Agent in the Reductive Amination.

NaH2PO2 was found to promote reductive amination. Being nontoxic, stable, environmentally benign, and available in bulk amounts, this reducing agent showed a powerful potential to compete with classical reductants applied in the target process. An E factor of 1 was achieved for the substrate scope. Different carbonyl compounds reacted with amines under the developed conditions. The reaction demonstrated a great compatibility with a wide range of functional groups. Reaction conditions were scaled up to 200-fold.

Synthesis, crystal structure and catalytic activity in reductive amination of di-chlorido-(η6-p-cymene)(2'-di-cyclo-hexyl-phosphanyl-2,6-di-meth-oxy-biphen-yl-κP)ruthenium(II).

The title compound, [RuCl2(C10H14)(C26H35O2P)] (I), crystallizes in the monoclinic space group P21/c with two crystallographically independent mol-ecules (A and B) in the asymmetric unit. The geometries of both mol-ecules are very similar and distinguished only by the twist angles of the two benzene rings in the phosphine substituents [89.54 (14) and 78.36 (14)° for mol-ecules A and B, respectively]. The Ru atoms have classical pseudo-tetra-hedral piano-stool coordination environments. The conformation of each mol-ecule is stabilized by intra-molecular C-H⋯O and C-H⋯Cl hydrogen bonds and C-H⋯π inter-actions. The two mol-ecules are linked by a C-H⋯Cl hydrogen bond. In the crystal, the mol-ecules are further linked by C-H⋯ π inter-actions, forming -A-B-A-B- chains propagating along the a-axis direction. Complex I is an active catalyst for reductive amination reaction. The catalytic activity of this complex can be explained by the lability of the p-cymene ligand, which can be replaced by two-electron ligands such as CO or amine.

Dichotomy of Reductive Addition of Amines to Cyclopropyl Ketones vs Pyrrolidine Synthesis.

An interesting catalytic dichotomy was discovered: switching between simple ligand-free catalysts leads to fundamentally different outcomes of reductive reaction between amines and α-carbonylcyclopropanes. Whereas a rhodium catalyst leads to the traditional reductive amination product, ruthenium catalysis enables a novel reaction of pyrrolidine synthesis via ring expansion. The protocols do not require an external hydrogen source and employ carbon monoxide as a deoxygenative agent. The developed methodologies are perfectly compatible with a number of synthetically important functionalities such as ester, carboxyl, bromo, and Cbz moieties.