Amination Of Ketones Research Articles

ChemInform Abstract: Transition‐Metal‐Free Oxidative α‐C—H Amination of Ketones via a Radical Mechanism: Mild Synthesis of α‐Amino Ketones.

A transition-metal-free direct α-C–H amination of ketones has been developed using commercially available ammonium iodide as the catalyst and sodium percarbonate as the co-oxidant. A wide range of ketone ((hetero)aromatic or nonaromatic ketones) and amine (primary/secondary amines, anilines, or amides) substrates undergo cross-coupling to generate synthetically useful α-amino ketones. The mechanistic studies indicated that a radical pathway might be involved in the reaction process. The utility of the method is highlighted through a concise one-step synthesis of the pharmaceutical agent amfepramone.

Selective Synthesis of Primary Amines by Reductive Amination of Ketones with Ammonia over Supported Pt catalysts

AbstractSupported platinum catalysts are studied for the reductive amination of ketones under ammonia and hydrogen. For a model reaction with 2‐adamantanone, Pt‐loaded MoOx/TiO2 (Pt‐MoOx/TiO2) shows the highest yield of primary amine. The catalyst is effective for the selective transformation of various aliphatic and aromatic ketones to the corresponding primary amines, which demonstrates the first example of the selective synthesis of primary amines by this reaction. The yield of the amine increases with increase in the negative shift of the CO stretching band in the infrared spectra of adsorbed acetone on the catalysts, suggesting that Lewis acid sites on the support material play an important role in this catalytic system.

One-pot asymmetric reductive amination of ketones induced by polyfluoroalkanesulfinamide

Abstract Using chiral 2-chloro-1,1,2,2-tetrafluoroethane-1-sulfinamide as the auxiliary, an efficient one-pot procedure for the asymmetric reductive amination of ketones was achieved in the presence of sodium borohydride. Both aromatic and aliphatic ketones reacted well to give the corresponding sulfinyl amides in good yields with excellent diastereoselectivities.

Iridium-catalyzed asymmetric reductive amination of ketones using an amidophosphite ligand

A direct iridium-catalyzed asymmetric reductive amination of ketones using an amidophosphite ligand was accomplished for the first time. A new one-step approach to the preparation of biologically active pyrazinocarbazoles was developed.

Engineering of Amine Dehydrogenase for Asymmetric Reductive Amination of Ketone by Evolving Rhodococcus Phenylalanine Dehydrogenase

Triple mutant K66Q/S149G/N262C (TM_pheDH) of Rhodococcus phenylalanine dehydrogenase (pheDH) was engineered by directed evolution as the first enzyme for the highly enantioselective reductive amination of phenylacetone 1 and 4-phenyl-2-butanone 3, giving (R)-amphetamine 2 and (R)-1-methyl-3-phenylpropylamine 4 in >98% ee, respectively. The new amine dehydrogenase TM_pheDH with special substrate specificity is a valuable addition to the amine dehydrogenase family with very limited number, for asymmetric reductive amination of ketone, an important reaction in sustainable pharmaceutical manufacturing. Molecular docking provided insight into the role of key mutations of pheDH, being useful for engineering new amine dehydrogenases with higher activity and unique substrate scope.

ChemInform Abstract: Synthesis and Characterization of Bisoxazolines‐ and Pybox‐Copper(II) Complexes and Their Application in the Coupling of α‐Carbonyls with Functionalized Amines.

AbstractThe copper‐catalyzed amination of ketones (I) and esters (IV) is reported [30 examples].

Phytoextracted mining wastes for ecocatalysis: Eco-Mn®, an efficient and eco-friendly plant-based catalyst for reductive amination of ketones

Recycling of plant wastes derived from phytoextraction constituted the raw material for efficient and eco-friendly manganese catalyzed aminoreduction.

Asymmetric Reductive Amination of Ketones

Asymmetric Reductive Amination of Ketones

ChemInform Abstract: One‐Pot Parallel Synthesis Approach to Secondary Amines Based on the Reductive Amination of Ketones.

AbstractA set of arbitrarily chosen acyclic and cyclic, alkyl and aryl ketones as well as amines (twenty each) are converted in this one‐pot approach to build up a library of secondary amines.

Metabolically driven equilibrium shift of asymmetric amination of ketones by ω-transaminase using alanine as an amino donor.

Removal of a side product to overcome unfavorable equilibrium is a prerequisite for the asymmetric amination of ketones using ω-transaminase (ω-TA). Alanine has been preferred as an amino donor because its deamination product (i.e. pyruvate) is easily removable by several enzymatic methods. Here, we demonstrated that the removal of pyruvate by an innate metabolic pathway could afford equilibrium shift of the ω-TA reactions.

Cooperative Catalysis with Iron and a Chiral Brønsted Acid for Asymmetric Reductive Amination of Ketones

AbstractThe direct asymmetric reductive amination (DARA) of ketones with anilines is described by combining a chiral Brønsted acid (TRIP) and the non‐chiral Knölker iron complex as the catalyst system. In situ‐formed imines are reduced with molecular hydrogen to give chiral amines in high yields (90%) and enantioselectivities of up to 99% ee.magnified image

Transition-metal-free oxidative α-C-H amination of ketones via a radical mechanism: mild synthesis of α-amino ketones.

A transition-metal-free direct α-C-H amination of ketones has been developed using commercially available ammonium iodide as the catalyst and sodium percarbonate as the co-oxidant. A wide range of ketone ((hetero)aromatic or nonaromatic ketones) and amine (primary/secondary amines, anilines, or amides) substrates undergo cross-coupling to generate synthetically useful α-amino ketones. The mechanistic studies indicated that a radical pathway might be involved in the reaction process. The utility of the method is highlighted through a concise one-step synthesis of the pharmaceutical agent amfepramone.

Self-catalyzed direct amidation of ketones: A sustainable procedure for acetaminophen synthesis

High yielding amination of ketones and benzaldehyde in acid-less conditions has been conducted on several ketones to achieve amides and nitriles. The reactivity of the selected substrates showed to depend on both oximation and Beckmann rearrangement reaction rates. Oximation allows the in-situ production of hydrochloric acid that enables Beckmann rearrangement of the oxime to form the corresponding amide or nitrile. It is noteworthy that, using this one-pot synthetic approach, N-acetyl-4-aminophenol (acetaminophen drug), can be easily synthesized starting from 4-hydroxy-acetophenone in high yield. Acetanilide and ε-caprolactam can be also efficiently synthesized employing this synthetic procedure.

ChemInform Abstract: Primary Amines by Transfer Hydrogenative Reductive Amination of Ketones by Using Cyclometalated IrIII Catalysts.

AbstractAn easy way to prepare primary amines is demonstrated by direct reductive amination of various ketones.

One-Pot Parallel Synthesis Approach to Secondary Amines Based on the Reductive Amination of Ketones

A combination of a condensation mixture [a Lewis acid, Ti(O<i>i</i>-Pr)₄, and a water scavenger, 1-(trimethylsilyl)-2-pyrrolidinone] and a simple reductant (NaBH₄) provides an efficient one-pot approach to parallel synthesis of secondary amines by the reductive amination of ketones. The approach demonstrated its applicability to a variety of substrates with different degree of hindrance of an amino or a carbonyl group affording products in moderate to high yields.

Design of a novel redox biocatalyst to specification (363.3)

Recently, we obtained the first amine dehydrogenases, termed L‐AmDH and F‐AmDH, from leucine DH [1] and phenylalanine DH [2], respectively, allowing direct reductive amination of ketones to chiral amines.Starting from a scaffold devoid of such activity, a robust AmDH has been evolved with a single two‐site library allowing for the direct production of (R)‐1‐(4‐fluorophenyl)‐propyl‐2‐amine from para‐fluoro phenyl acetone with a kcat value of 6.85 s‐1 at 25oC. Only (R)‐amine was formed (&gt; 99.8% e.e.), showing that perfect enantioselectivity of the template was conserved.Successful domain shuffling created a chimeric amine DH with enhanced substrate specificity that allows to accommodate sterically very demanding side chains, such as adamantly groups. We will elucidate the impact of restricted libraries in the evolution towards higher activity and broader specificity.Many interesting substrates feature low solubility in aqueous solution. We describe how utilizing a two‐phase system can also lead to pinpointing broadened substrate specificity, as substrate candidates that were previously missed, can register as hits in the search.

ChemInform Abstract: Development of a Chiral Bis(guanidino)iminophosphorane as an Uncharged Organosuperbase for the Enantioselective Amination of Ketones.

AbstractNewly developed bis(guanidino)iminophosphoranes possess the highest basicity among chiral organocatalysts reported to date.

Primary Amines by Transfer Hydrogenative Reductive Amination of Ketones by Using Cyclometalated IrIII Catalysts

Cyclometalated iridium complexes are found to be versatile catalysts for the direct reductive amination (DRA) of carbonyls to give primary amines under transfer-hydrogenation conditions with ammonium formate as both the nitrogen and hydrogen source. These complexes are easy to synthesise and their ligands can be easily tuned. The activity and chemoselectivity of the catalyst towards primary amines is excellent, with a substrate to catalyst ratio (S/C) of 1000 being feasible. Both aromatic and aliphatic primary amines were obtained in high yields. Moreover, a first example of homogeneously catalysed transfer-hydrogenative DRA has been realised for β-keto ethers, leading to the corresponding β-amino ethers. In addition, non-natural α-amino acids could also be obtained in excellent yields with this method.

ChemInform Abstract: Stereoselective Direct Reductive Amination of Ketones with Electron‐Deficient Amines Using Re2O7/NaPF6 Catalyst.

AbstractThe first examples of direct reductive amination of ketones with amines bearing electron‐withdrawing substituents are described.

Development of a Chiral Bis(guanidino)iminophosphorane as an Uncharged Organosuperbase for the Enantioselective Amination of Ketones

Chiral bis(guanidino)iminophosphoranes were designed and synthesized as chiral uncharged organosuperbase catalysts that facilitate activation of less-acidic pro-nucleophiles. The newly developed bis(guanidino)iminophosphoranes, which possess the highest basicity among chiral organocatalysts reported to date, were proven to be a superb class of chiral organosuperbases by reaction of azodicarboxylates with 2-alkyltetralones and their analogues as the less acidic pro-nucleophiles.