Transition-Metal-Catalyzed Reductive Amination Employing Hydrogen

Abstract

The reductive amination, the reaction of an aldehyde or a ketone with ammonia or an amine in the presence of a reducing agent and often a catalyst, is an important amine synthesis and has been intensively investigated in academia and industry for a century. Besides aldehydes, ketones, or amines, starting materials have been used that can be converted into an aldehyde or ketone (for instance, carboxylic acids or organic carbonate or nitriles) or into an amine (for instance, a nitro compound) in the presence of the same reducing agent and catalyst. Mechanistically, the reaction starts with a condensation step during which the carbonyl compound reacts with ammonia or an amine, forming the corresponding imine followed by the reduction of the imine to the alkyl amine product. Many of these reduction steps require the presence of a catalyst to activate the reducing agent. The reductive amination is impressive with regard to the product scope since primary, secondary, and tertiary alkyl amines are accessible and hydrogen is the most attractive reducing agent, especially if large-scale product formation is an issue, since hydrogen is inexpensive and abundantly available. Alkyl amines are intensively produced and use fine and bulk chemicals. They are key functional groups in many pharmaceuticals, agro chemicals, or materials. In this review, we summarize the work published on reductive amination employing hydrogen as the reducing agent. No comprehensive review focusing on this subject has been published since 1948, albeit many interesting summaries dealing with one or the other aspect of reductive amination have appeared. Impressive progress in using catalysts based on earth-abundant metals, especially nanostructured heterogeneous catalysts, has been made during the early development of the field and in recent years.

Highly selective and robust single-atom catalyst Ru1/NC for reductive amination of aldehydes/ketones

“…The reductive amination of aldehydes/ketones to produce primary amines is such a reaction that involves the activation of both hydrogen and NH 3 molecules 14 . In the past few years, this reaction has attracted intensive attention attributed to the broad applications of primary amines as key building blocks for pharmaceuticals, agrochemicals, polyamides, and other fine chemicals 15 , 16 .…”

General Synthesis of Secondary Alkylamines by Reductive Alkylation of Nitriles by Aldehydes and Ketones

“…Differently substituted secondary alkylamines, examples of pharmaceuticals are shown in Scheme 1 A, are challenging to synthesize. Most of the existing catalytic methods, such as borrowing hydrogen or hydrogen autotransfer, [4, 5] reductive amination, [6, 7] hydroaminomethylation [8] and hydroamination, [9, 10] albeit intensively investigated, start already from an amine (Scheme 1 B) and are restricted regarding the synthesis of secondary alkylamines [11] . The hydrogenation of amides is an alternative (Scheme 1 C), since it does not require an amine as starting material, [12, 13] but again the synthesis of differently substituted secondary alkylamines is rarely reported [14] .…”

Crystal Structures and Catalytic Mechanism of l‐erythro‐3,5‐Diaminohexanoate Dehydrogenase and Rational Engineering for Asymmetric Synthesis of β‐Amino Acids

“…[2] Among them, the reductive amination of bketo or b-hydroxyl carboxylic acids and derivatives represents an attractive straightforward approach to access b-amino acids and derivatives. [3] Recently,d irect amination of bhydroxyl acid esters was achieved using aborrowing hydrogen methodology involving cooperative catalysis of ar uthenium catalyst and aBrønsted acid additive. [4] Biocatalytic reductive amination of b-keto acids has been reported using transaminases,w hich catalyze the amino transfer from an amino acid or amine to b-keto acids to give optically active b-amino acids.…”

“…However,c ompared to a-amino acid dehydrogenase (a-AADH), the b-counterpart has been much less studied. To the best of our knowledge,t he only reported b-AADH is l-erythro-3,5-diaminohexanoate dehydrogenase (3,EC.1.4.1.11), which has been identified to participate in the degradation pathway of lysine from some bacterial species. [9] This NAD(P)H-dependent enzyme catalyzes the reversible deamination/ amination reaction between (3S,5S)-diaminohexanoate (1a)a nd 3-keto-5-aminohexanoate (1b, Scheme 1).…”