Transfer hydrogenation of imines

Samec and Backvall found that the dinuclear Shvo complex catalyzes the transfer hydrogenation of imines using benzene as solvent and isopropanol as the hydrogen source (Eq. (45)) [76]. These catalytic hydrogenations were typically carried out at 70 °C, and gave >90% yields of the amine in 4 h or less. 

Asymmetric transfer hydrogenation of imines catalyzed by chiral arene-Ru complexes achieves high enantioselectivity (Figure 1.34). Formic acid in aprotic dipolar solvent should be used as a hydride source. The reaction proceeds through the metal-ligand bifunctional mechanism as shown in the carbonyl reduction (Figure 1.24). 

Figure 1.34. Asymmetric transfer hydrogenation of imines catalyzed by chiral Ru complexes.

Anomalous concentration dependence observed in the asymmetric transfer hydrogenation of imines with formic acid, catalysed by chiral rhodium-diamine complexes, has been attributed to the participation of both reactant and product in the formation of formate salt. The probable resting state of the catalyst is a rhodium hydride species.373... 

Phosphoric acid catalysts, bearing bulky groups, have been devised for the asymmetric transfer hydrogenation of imines with Hantsch ester. With the catalyst (14), (g) enantioselectivity up to 93% has been achieved in the reduction of aromatic imines. 

The catalytic, asymmetric hydrogenations of alkenes, ketones and imines are important transformations for the synthesis of chiral substrates. Organic dihydropyridine cofactors such as dihydronicotinamide adenine dinucleotide (NADH) are responsible for the enzyme-mediated asymmetric reductions of imines in living systems [86]. A biomimetic alternative to NADH is the Hantzsch dihydropyridine, 97. This simple compound has been an effective hydrogen source for the reductions of ketones and alkenes. A suitable catalyst is required to activate the substrate to hydride addition [87-89]. Recently, two groups have reported, independently, the use of 97 in the presence of a chiral phosphoric acid (68 or 98) catalyst for the asymmetric transfer hydrogenation of imines. 

Scheme 6.12 Phosphoric acid-catalyzed transfer hydrogenations of imines.

Phosphoric Acid-Catalyzed Transfer Hydrogenations of Imines [95] (pp. 230 and 397)... 

Hoffmann S, Seayad AM, List B (2005) A powerful Brpnsted acid catalyst for the organocatalytic asymmetric transfer hydrogenation of imines. Angew Chem Int Ed Engl 44 7424-7427... 

Bianchini, C., Glendenning, L. Ruthenium(ll)-catalyzed asymmetric transfer hydrogenation of ketones using a formic acid-triethylamine mixture. Asymmetric transfer hydrogenation of imines. Chemtracts 1997, 10, 333-338. 

For an overview of transfer hydrogenation of imines, see Samec. J.S.M., Backvall,... 

Table 6,10 Asymmetric transfer hydrogenation of imines using HCO2H/NEt3 as the hydrogen source.

Table 6.11 Rhodium catalyzed asymmetric transfer hydrogenation of imines.

Much like the direct hydrogenation of imines, the transfer hydrogenation of imines has seen a number of recent attempts to use less toxic solvents and to recycle catalysts, and many of the same methods employed to improve the former reaction have also been applied to the latter. 

Syntheses Using the Asymmetric Transfer Hydrogenation of Imines as a Key Step... 

The past 35 years have seen both the asymmetric hydrogenation and asymmetric transfer hydrogenation of imines develop into useful methods for the synthesis of chiral amines. Particularly, focused research over the past 15 years has led to highly enantioselective examples of both reaction types and has added aza aromatics, activated imines, and iminium cations to their purview. In addition, the asymmetric hydrogenation and asymmetric transfer hydrogenation of imines have both been apphed to total syntheses. Because they are necessarily isomeri... 

Ligands with one R2NH terminus and one ArSO2NR terminus have only recently been used in the asymmetric transfer hydrogenation of imines. See Martins, J.E.D.. Clarkson, G.J.. Wills, M. (2009) Org. Lett. 11, 847. 

Hydrogenation and Transfer Hydrogenation of Imines and Related Compounds... 

The asymmetric reduction of imines and iminium species can be achieved using organocatalysts. The transfer hydrogenation of imines is catalysed by acids and this has led to the development of biomimetic asymmetric reductions using enan-tioselective Bronsted acids in combination with Hantzsch esters as a hydride... 

A new approach to stereoselective transfer hydrogenation of imines was the application of chiral phosphoric acid esters as organocatalysts [50-52]. The mechanism is based on the assumption that the imine is protonated by a chiral Bronsted acid, which acts as the catalyst. The resulting diastereomeric iminium ion pairs, which may be stabilized by hydrogen bonding, react with the Hantzsch dihydropyridine at different rates to give an enantiomerically enriched amine and a pyridine derivative [50-52]. The exact mechanism is still under discussion however computational density functional theory (DFT) studies ]53, 54] suggest a three-point contact model. ... 

Three classes of catalysts have been studied for the asymmetric hydrogenation of imines. One class of catalyst is generated from late transition metal precursors and bisphosphines. These catalysts have typically been generated from rhodium and iridium precursors. A second class of catalyst is based on the chiral titanocene and zirconocene systems presented in the previous section on the asymmetric hydrogenation of unfunctionalized olefins. The third class of catalyst is used for the transfer hydrogenation of imines and consists of ruthenium or rhodium complexes containing diamine, amino tosylamide, or amino alcohol ligands. " ... 

Asymmetric Transfer Hydrogenation of Imines. In spite of the great importance of optically active amines for pharmaceutical and agrochemical industries, the ATH of C=N imine bonds has been much less studied than that of ketone bonds (278,280,284,289,340). Cyclic imines are reduced with greater ee values than their acyclic counterparts. The existence of geometrical isomers for the latter is based on the encountered difference in selectivity. 

Asymmetric Transfer Hydrogenation of Imines in Water. The catalytic ATH of imines in aqueous solution has been, so far, much less studied than that of the ketones (289). The tried imines are shown in Figure 89. 

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