Synthesis of Primary Amines by One-Pot Reductive Amination of Aldehydes

We report here a novel, one-pot, two-step reductive amination of aldehydes for the atom-economical synthesis of primary amines. The amination step has been carried out with hydroxylammonium chloride and does not require the use of a base. In the subsequent reduction step, a metal zinc/hydrochloride acid system has been used. This method is applicable to both aliphatic and aromatic aldehydes. The operational simplicity, the short reaction times, and the mild reaction conditions add to the value of this method as a practical alternative to the reductive amination of aldehydes.

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Direct Reductive Amination of Aldehydes and Ketones with 2,4-Ionene-Based Borohydride Exchange Resin as a Novel Polymer-Supported Reducing Agent

Direct reductive amination of aldehydes and ketones were accomplished efficiently using high-capacity, ionene-based, polymer-supported borohydride reagent in isopropyl alcohol at reflux under neutral conditions. The reagent is easily prepared by mixing aqueous solution of 2,4-ionene bromide with an alkaline solution of sodium borohydride at room temperature. The generality of reaction was established using both aliphatic and aromatic aldehydes, ketones, and amines.     

Fast Reductive Amination by Transfer Hydrogenation “on Water”

Reductive amination of various ketones and aldehydes by transfer hydrogenation under aqueous conditions has been developed, by using cyclometallated iridium complexes as catalysts and formate as hydrogen source. The pH value of the solution is shown to be critical for a high catalytic chemoselectivity and activity, with the best pH value being 4.8. In comparison with that in organic solvents, the reductive amination in an aqueous phase is faster, and the molar ratio of the substrate to the catalyst (S/C) can be set as high as 1×10⁵, the highest S/C value ever reported in reductive amination reactions. The catalyst is easy to access and the reaction is operationally simple, allowing a wide range of ketones and aldehydes to react with various amines in high yields. The protocol provides a practical and environmental friendly new method for the synthesis of amine compounds.     

Iridium-Catalyzed Direct Reductive Amination of Ketones and Secondary Amines: Breaking the Aliphatic Wall

Direct reductive amination (DRA) is a ubiquitous reaction in organic chemistry. This transformation between a carbonyl group and an amine is most often achieved by using a super stoichiometric amount of hazardous hydride reagents, thus being incompatible with many sensitive functional groups. DRA could also be achieved by means of chemo- or biocatalysis, thereby attracting the interest of industry as well as academic laboratories due to the virtually perfect atom economy. Although DRAs are well-established for substrate pairs such as aldehydes with either 1° or 2° amines as well as ketones with 1° amines, the current methodologies are limited in the case of ketones with 2° amines. Herein, we present a general DRA protocol that overcomes this major limitation by means of iridium catalysis. The applicability of the methodology is demonstrated by accessing an unprecedented range of biologically relevant tertiary amines starting from both aliphatic ketones and aliphatic amines. The choice of a disphosphane ligand (Josiphos A or Xantphos) is essential for the success of the transformation.     

Reductive Amination of Aldehydes and Ketones with Primary Amines by Using Lithium Amidoborane as Reducing Reagent

A variety of secondary amines were obtained in high isolated yields in the reductive amination of aldehydes and ketones by using lithium amidoborane as reducing agent. Compared to ammonia borane, lithium amidoborane has higher reducibility, and thus, exhibits faster reaction rate.     

Reductive Amination of Carbonyl Compounds with Ammonia and Hydrogenation of Nitriles to Primary Amines with Heterogeneous Cobalt Catalysts

Reductive amination of aldehydes/ketones with aqueous NH3 and hydrogenation of nitriles to primary amines with Co catalysts were reported. Co@NC-700 exhibited remarkable activity and high selectivity for the reductive amination of aldehydes/ketones with aqueous NH3 and the hydrogenation of nitriles to primary amines. Several primary amines can be obtained with good to excellent yields via the reductive amination of aldehydes/ketones and the hydrogenation of nitriles. The nitrogen-doped carbon(C)-supported Co@NC-700 metal catalyst was prepared via the pyrolysis of bioMOF Co/adenine in activated C. Co@NC-700 can be reused five times without evident loss of activity.     

Air Stable Iridium Catalysts for Direct Reductive Amination of Ketones

Half-sandwich iridium complexes bearing bidentate urea-phosphorus ligands were found to catalyze the direct reductive amination of aromatic and aliphatic ketones under mild conditions at 0.5 mol % loading with high selectivity towards primary amines. One of the complexes was found to be active in both the Leuckart–Wallach (NH₄CO₂H) type reaction as well as in the hydrogenative (H₂/NH₄AcO) reductive amination. The protocol with ammonium formate does not require an inert atmosphere, dry solvents, as well as additives and in contrast to previous reports takes place in hexafluoroisopropanol (HFIP) instead of methanol. Applying NH₄CO₂D or D₂ resulted in a high degree of deuterium incorporation into the primary amine α-position.     

Reductive Amination of Aldehydes and Ketones in a Heterogeneous System in THF and under Solvent-Free Conditions Using Sodium Borohydride-Silica Phosphoric Acid

Summary. A chemoselective, fast, efficient, and high yielding method for the preparation of amines by reductive amination of aldehydes and ketones using sodium borohydride in the presence of silica phosphoric acid in THF and under solvent-free conditions at room temperature is described.     

General Reductive Amination of Aldehydes and Ketones with Amines and Nitroaromatics under H2 by Recyclable Iridium Catalysts

Heterogeneous iridium catalysts were prepared and applied for the reductive amination of aldehydes and ketones with nitroaromatics and amines using H₂ . The iridium catalysts were prepared by pyrolysis of ionic liquid 1‐methyl‐3‐cyanomethylimidazoulium chloride ([MCNI ]Cl) with iridium chloride (IrCl₃ ) in activated carbons. Iridium particles were well dispersed and stable in the N‐doped carbon materials from [MCNI ]Cl with activated carbon. The Ir@NC (600‐2h) catalyst was found to be highly active and selective for the reductive amination of aldehydes and ketones using H₂ and a variety of nitrobenzenes and amines were selectively converted into the corresponding secondary and tertiary amines. The Ir@NC (600‐2h) catalyst can be reusable several times without evident deactivation.     

One-pot reductive amination of aldehydes and ketones with α-picoline-borane in methanol, in water, and in neat conditions

A one-pot reductive amination of aldehydes and ketones with amines using α-picoline-borane as a reducing agent is described. The reaction has been carried out in MeOH, in H₂O, and in neat conditions in the presence of small amounts of AcOH. This is a highly efficient and mild procedure that is applicable for a wide variety of substrates. In particular, this is the first successful demonstration that this type of reaction can be carried out in water and in neat conditions.     

Reductive amination of ferrocenylformylpyrazoles

1-Aryl-3-ferrocenyl-4-formylpyrazoles were obtained from appropriate acetylferrocene arylhydrazones by the Vilsmeier—Haack reaction. Direct reductive amination of the resulting aldehydes with primary and secondary amines and amino acid esters in the presence of NaBH(OAc)₃ was studied.     

Reductive amination using ammonia borane

A variety of primary, secondary, and tertiary amines were prepared in 84-95% yields using ammonia borane for the reductive amination of aldehydes and ketones in the presence of titanium isopropoxide.     

Knölker's iron complex: an efficient in situ generated catalyst for reductive amination of alkyl aldehydes and amines

An aminated series: a well-defined iron-catalyzed reductive amination reaction of aldehydes and ketones with aliphatic amines using molecular hydrogen is presented. Under mild conditions, good yields for a broad range of alkyl ketones as well as aldehydes were achieved.     

Reductive Amination of Aldehydes and Ketones to Their Corresponding Amines with NaBH4 in Micellar Media

A variety of aliphatic and aromatic aldehydes and ketones were efficiently reduced to their corresponding amines when treated with primary and secondary amines and NaBH₄ in micellar media at room temperature under neutral conditions.     

Enantioselective organocatalytic reductive amination of aliphatic ketones by benzothiazoline as hydrogen donor

The chiral phosphoric acid-catalyzed enantioselective reductive amination of aliphatic ketones with aromatic amines was successfully achieved by the use of benzothiazoline as the hydrogen donor. Corresponding chiral aliphatic amines were obtained with excellent enantioselectivities.     

Reductive Amination of Aldehydes and Ketones with 2-(Tributylamino)-ethoxyborohydride

A new ionic liquid is presented as a medium and reducing agent for the reductive amination of aldehydes and ketones.     

Reductive Amination of Aldehydes and Ketones with 2-(Tributylamino)-ethoxyborohydride

Summary. A new ionic liquid is presented as a medium and reducing agent for the reductive amination of aldehydes and ketones.     

Reductive Amination of Aldehydes and Ketones to Their Corresponding Amines with NaBH<Subscript>4</Subscript> in Micellar Media

Summary. A variety of aliphatic and aromatic aldehydes and ketones were efficiently reduced to their corresponding amines when treated with primary and secondary amines and NaBH₄ in micellar media at room temperature under neutral conditions.     

Reductive Amination of Aromatic Aldehydes Using NADH Models

Reductive amination of aromatic aldehydes takes place when treated with equimolar amounts of aromatic amines and NADH model compounds in glacial acetic acid. Imines, the intermediates in the reaction were also reduced by NADH models in acetic acid.     

Reductive Amination of Aldehydes and Amines with an Efficient Pd/NiO Catalyst

By applying a simple Pd/NiO catalyst, the reductive amination of amines and aldehydes can progress efficiently under mild reaction conditions, and 24 substituted amines with different structures were synthesized with up to 98% isolated yields.