Highlights of Transition Metal‐Catalyzed Asymmetric Hydrogenation of Imines

Abstract

This Review deals with the asymmetric hydrogenation and asymmetric transfer hydrogenation of imines and some nitrogen‐containing heteroaromatic compounds to afford amines. Hydrogenation and transfer hydrogenation are covered in separate sections. Particular attention is devoted to the substrates, since this reaction is highly substrate dependent. In this way the general structural trends in imine hydrogenation are presented, highlighting the more challenging substrates. Since hydrogenation of acyclic and cyclic (including heteroaromatic) imines have some different features they are also presented separately. The catalytic systems are classified according to the metal, and focus on the most successful catalytic systems and metal–ligand combinations. The catalytic cycles for these hydrogenation processes are also proposed.

Ruthenium(II)-Arene Complexes of the Water-Soluble Ligand CAP as Catalysts for Homogeneous Transfer Hydrogenations in Aqueous Phase

“…Hydrogenation of imines and, in particular, cyclic imines is a worthy synthetic tool to obtain amines, that in turn are synthetic intermediates of great importance especially in pharmaceutical industry [25]. Among Ru catalysts described in the literature for this class of homogeneously catalyzed reaction, outstanding performances were obtained for example with Noyori's complex [RuCl(η 6 -p-cymene)(TsDPEN)] (TsDPEN=N-(p-toluene-sulfonyl)-1,2-diphenylethylenediamine), using a formic acid-triethylamine azeotropic mixture as reducing agent [26,27].…”

“…Recently, we reported on the synthesis of a new class of half-sandwich ruthenium arene complexes bearing a higher homologue of PTA, namely 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane, CAP [22]. As PTA, this compound is a white, air-stable solid under standard conditions, and it is moderately water soluble with S(H 2 O) 25 • C = 20 g L −1 , about one order of magnitude lower than for PTA. Although structurally very similar to PTA, CAP has a higher cage flexibility due to the presence of two CH 2 spacers between the N atoms instead of one [23,24].…”

Reaction Monitoring in Multiphase Systems: Application of Coupled In Situ Spectroscopic Techniques in Organic Synthesis

“…The heterogeneously catalyzed asymmetric hydrogenation of C=N double bonds remains a challenge, and indeed asymmetric imine hydrogenation has been restricted to homogeneous catalysis for many years. Novel approaches for the synthesis of such amines via transition metal catalysis [47][48][49] have been developed, wherein imines are key intermediates. The transition metal-based approaches for the asymmetric hydrogenation of acyclic imines can be divided into catalysts that work with molecular hydrogen and those suitable for transfer hydrogenation.…”

Catalytic Asymmetric Hydrogenation of 3-Substituted Benzisoxazoles

“…One involves the acylation of the imine NH with Cbz-OSu to form intermediate 10 [59,60], which is reduced to 8 by hydrogen through the ruthenium catalysis (path a). In the other possible pathway, the hydrogenation of C-N double bond in 3 occurs prior to the Cbz-protection of the nitrogen atom (path b) [61]. To ascertain these two possibilities, the following reactions were conducted by using the imine 3a as the substrate.…”