Hantzsch esters hydride donors

In 2001, we reasoned that this catalysis strategy might be applicable to the conjugate reduction of a, 3-unsaturated carbonyl compounds if a suitable hydride donor could be identified (Scheme 18). Hantzsch ester 11 seemed to be particularly promising since its reaction with preformed a, 3-unsaturated iminium ions had already been established (Makino et al. 1977 Baba et al. 1980). 

Nature makes use of NADH (reduced nicotinamide adenine dinucleotide) as a cofactor for enantioselective biochemical hydrogenations, which are typical hydride-transfer reactions. Dihydropyridines and benzimidazolines derivatives are active hydride donors due to the presence of the nitrogen atom and the ability of the molecule to undergo aromatisation. Organocatalytic enantioselective reductions carried out using hydride donors has been studied, and effective reductions have been achieved with imidazoli-dinone organocatalysts, both with a,p unsaturated aldehydes and ketones. Generally, a stoichiometric quantity of reductant (Hantzsch ester 4) is required for these transformations (Scheme 18.5). 

A bio-inspired catalyst comprising a combined organic hydride donor with metal centre has been reported for TH of imines. A previously used catalyst relied on a Hantzsch ester, but the newer derivative benefits from easier preparation and greater accessibility. Yields are high for the Rh complex containing all the components, and more than for the Ir complex or the complex containing the phenanthroline ligand alone (Fig. 38) [122, 123]. 

Zheng, C. You, S.-L. Transfer hydrogenation with Hantzsch esters and related organic hydride donors. Chem. Soc. Rev. 2012, 41, 2498-2518. 

Figure 9.9. Reductive animation catatyzed by Eco-Mn by using a Hantzsch ester as a hydride donor...

Double bonds conjugated with aldehydes or ketones can selectively be reduced with two different catalytic systems. Both systems use Hantzsch ester derivatives (HEH, 1) as hydride donor, analogous to nicotinamide adenine dinucleotide (NADH, 2), nature s reducing agent (Figure 32.1). These esters were first prepared by Hantzsch in 1882 from ethyl acetoacetate, formaldehyde, and ammonia. The... 

Generally, these reductions can be divided in two classes vide supra), similarly to the C=0 reductions. The first and more prominent type makes use of silanes as hydride donors and chiral Lewis bases as their activators. The second type is based on the combination of Hantzsch esters and chiral Brpnsted acids. 

The first enantioselective imine reduction using Hantzsch esters as hydride donor was carried our by Singh and Batra in Using cysteine-derived catalysts, only moderate,... 

The hydride donor ability of Hantzsch ester 4a has been experimentally determined to be slightly higher than that of N-benzylnicotinamide, both being comparable to the borane-triethylamine complex [17]. Together with trichlorosilane [18], Hantzsch esters 4 are the reagents of choice to effect asynunetric reductions using chiral organocatalysts. 

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