Imino Reductions by Transfer Hydrogenation

Abstract

11 History and BackgroundIn contrast to ketones, and in particular with respect to asymmetric reductions, the reduction of compounds containing C = N bonds has remained relatively underdeveloped. Some signifi cant breakthroughs have, however, been reported in the last ten years. This chapter will review reductions through metal hydride complexes, " Meerwein -Ponndorf -Verley ( MPV ) type " reductions, and other methods including transfer hydrogenation with organocatalysts and asymmetric LeuckartWallach aminations of ketones. Although there will be discussion of mechanistic aspects, the main focus of this review will be on more recent synthetic applications. The reader ' s attention is also directed to a number of recent useful reviews of this area [1] . Mechanisms of C= N Bond Reduction by Transfer HydrogenationUsing either organic or organometallic catalysts, transfer hydrogenation of imines and other C = N bond -containing substrates, is most commonly carried out using isopropanol, formic acid or a formate salt as the hydrogen source. The most commonly, but not exclusively, used metals are ruthenium, rhodium and iridium.The mechanism of the transfer hydrogenation of imines has been the subject of some extended synthetic, computational and mechanistic studies. The tutorial review by B ä ckvall [1f] provides a very good summary of this. An excellent review by Morris [1c] also contains an incisive overview of hydrogenation and transfer hydrogenation and provides a very logical nomenclature for the possible reduction reaction pathway.The mechanisms that may be considered for imine reduction are the same as for ketone reductions and may be divided into two broad classes (Figure 11.1 ). In the fi rst of these, the MPV reduction or its reverse (Oppenauer oxidation), a metal

Chiral β-Amino Alcohols as Ligands for the Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of N-Phosphinyl Ketimines

“…Since those ligands have shown to give excellent results in the ruthenium-catalyzed asymmetric transfer hydrogenation of ketones [12][13][14][15][16][17][18][19] and N-sulfinylimines [38][39][40][41] in isopropyl alcohol, we decided to investigate if they could also be applied to the reduction of N-phosphinyl ketimines by the same methodology. One of the most noteworthy chiral β-amino alcohols in the ATH of both ketones and N-sulfinyl imines is cis-1-amino-2-indanol [50].…”

“…The ATH protocol presents several advantages: it is operationally simple, proceeds under mild reaction conditions, generally uses low catalyst loadings and avoids the handling of hazardous chemicals such as metallic hydrides or hydrogen gas. The ATH of prochiral ketones affords enantiomerically enriched secondary alcohols with excellent results [12][13][14][15][16][17][18][19]. Nevertheless, the asymmetric reduction of iminic compounds by transfer hydrogenation yielding chiral amines still remains underdeveloped and represents a challenging objective [20,21].…”

“…Although the transfer hydrogenation protocol has been already applied to the reduction of different iminic substrates bearing alkyl [18], benzyl [17,18], aryl [17,18], sulfonyl [13,18,37] or sulfinyl [38][39][40][41] groups attached to the nitrogen atom, there are only a few examples on the use of N-phosphinyl imines as substrates [18,42]. In the last years, we have been interested in the use of β-amino alcohols as ligands for ruthenium complexes used as catalysts for the ATH of imines, especially N-(tert-butylsulfinyl)imines [38][39][40][41].…”

Glycerol: A promising Green Solvent and Reducing Agent for Metal-Catalyzed Transfer Hydrogenation Reactions and Nanoparticles Formation

“…TH is recognized as an efficient reduction method of unsaturated organic compounds (ketones, aldehydes, imines, olefins, etc.) and constitutes a safer alternative to the classical catalytic hydrogenations using highly flammable molecular hydrogen [38][39][40][41][42]. Replacing the most commonly employed hydrogen sources in TH reactions, i.e., 2-propanol or formic acid/triethylamine mixtures, by glycerol results not only economically appealing but also more environmentally friendly.…”

Synthesis and Screening of C1‐Substituted Tetrahydroisoquinoline Derivatives for Asymmetric Transfer Hydrogenation Reactions

“…[1][2][3] In these reactions transfer hydrogenation has been applied to ketones and imines. [4,5] In particular it has been very successful for the reduction of a range of unsymmetrical ketones. Nevertheless, there is still significant interest in the development of new varieties of chiral backbones as potential ligands in asymmetric catalysis.…”