Asymmetric Reductive Amination

Abstract

Despite its long history and common usage of the term, reductive amination has remained underdeveloped. Many studies are available regarding racemic reductive amination, but only B€ orner and Tararov have provided summaries of the asymmetric version [1]. In this chapter we provide an overview of the available methods and achievements since the first demonstrated enantioselective reductive amination by Blaser in 1999 [2].Compared to the large volume of reports detailing asymmetric imine reduction, only a small number of publications are available regarding asymmetric reductive amination. Reductive amination remains less developed than the field of imine reduction due in great part to the incompatibility of transition metal hydride catalysts in the presence of ketones (alcohol by-product formation) and/or catalyst inhibition arising from amine starting material or amine product complexation with a catalytically active transition metal species [3]. Future method development will surely require striking the right balance between these competing nonproductive reaction pathways.Before discussing the relevant literature, a few qualifiers are mentioned and discussed. Reductive amination is sometimes incorrectly associated with the reduction of preformed imines and derivatives thereof. Reductive amination, by definition, is only the one-pot conversion of a ketone to an amine in which a reductant coexists in the presence of a ketone starting material [4]. The term indirect reductive amination is occasionally used, but can be more tersely and accurately described as imine reduction [5]. The reader will note that depending on the perspective one takes for the transformation, the term reductive amination is applied when considering the reaction course of the ketone starting material, and the term reductive alkylation is applied when describing the starting amines conversion to the product amine.Included in this section are procedures that are not classified as reductive amination, but are also not imine reductions in the sense that an imine has been isolated, here isolation means a work-up or distillation has been performed before the

Mechanistically Guided Design of Ligands That Significantly Improve the Efficiency of CuH-Catalyzed Hydroamination Reactions

“…9 These compounds are traditionally prepared by transforming carbonyl compounds, amides or alkyl electrophiles into their corresponding amine products. 10 From a strategic standpoint, hydroamination reactions between olefins and electrophilic amine sources provide one of the most straightforward and general avenues to access these important motifs, especially since the precursors are typically stable, readily available, and easy to handle. 11…”

Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines Enabled by Ligand-Controlled Chemoselective Hydrocupration

“…1 Consequently, general methods for the synthesis of amines in optically pure form have long been regarded as an important objective for synthetic organic chemists. 1 Among the numerous techniques available, asymmetric hydrogenation 1,2 and biocatalysis 1,3 are often employed.…”

“…1 Consequently, general methods for the synthesis of amines in optically pure form have long been regarded as an important objective for synthetic organic chemists. 1 Among the numerous techniques available, asymmetric hydrogenation 1,2 and biocatalysis 1,3 are often employed. However, the addition of carbon nucleophiles to prochiral imines, 4 particularly Ellman’s chiral tert -butylsulfinimines, 4a often represents the method of choice for the preparation of free or protected chiral primary amines.…”

NHC–Cu-Catalyzed Addition of Propargylboron Reagents to Phosphinoylimines. Enantioselective Synthesis of Trimethylsilyl-Substituted Homoallenylamides and Application to the Synthesis of S-(−)-Cyclooroidin

“…1 An array of strategies has been introduced for the preparation of homoallylic amines; 2 catalytic reactions that furnish homopropargyl amines have been recently developed. 3 Homoallenylamines are another set of compounds of substantial potential utility; such entities present unique functionalization possibilities 4 that generate enantiomerically enriched derivatives not easily obtainable through manipulation of an allyl, an alkyne, or a propargyl group.…”