Asymmetric Hydrogen-transfer Reactions

A theoretical study of the [RuCle] -catalysed exchsm has been 

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Goldberg, K., Edegger, K., Kroutil, W. and Liese, A. (2006) Overcoming the thermodynamic limitation in asymmetric hydrogen transfer reactions catalyzed by whole cells. Biotechnology and Bioengineering, 95,192-198. 

In Figure 13.19 we have shown a route to L-699,392 published by Merck involving three steps based on homogeneous catalysts, viz. two Heck reactions and one asymmetric hydrogen transfer reaction, making first an alcohol and subsequently a sulphide [21], Stoichiometric reductions for the ketone function have been reported as well [22] and the Heck reaction on the left-hand side can be replaced by a classic condensation reaction. L-699,392 is used in the treatment of asthma and related diseases. 

The procedure for getting the polymer-bound ligands is very easy to reproduce. Three jS-functionalized aromatic ketones were successfully reduced to the corresponding alcohols by heterogeneous asymmetric hydrogen transfer reaction with formic acid-triethylamine azeotrope as the hydrogen donor. One of the product alcohols (19c) is an intermediate for the synthesis of optically active fluoxetine. 

Scheme 5 Noyori s catalyst for asymmetric hydrogen transfer reaction of ketones...

Simple reductions, hydrogenation, transfer hydrogenation, and asymmetric hydrogen transfer reactions are discussed in this section. 

Zassinovich G, Mestroni G, Gladiali S (1992) Asymmetric hydrogen transfer reactions promoted by homogeneous transition metal catalysts. Chem Rev 92(5) 1051-1069... 

Isopropanol can be used in the asymmetric hydrogen transfer reactions for two purposes first, as a cosolvent for improving the substrate solubility and second, as a cosubstrate for cofactor regeneration (substrate-coupled approach). For example, in the reduction of acetophenone by Candida viswanathii cells, addition of 10% (v/v) isopropanol led to a great increase of the substrate tolerance and a conversion of 90% compared to 9% in the control at a substrate concentration of 70 mM after lh[8]. 

Scheme 6.53 Asymmetric Heck and hydrogen-transfer reactions.

Other enantioselective reactions performed by microwave heating include asymmetric Heck reactions (Scheme 6.53 a) [109] and ruthenium-catalyzed asymmetric hydrogen-transfer processes (Scheme 6.53 b) [110]. 

As an alternative to the use of hydrogen gas, asymmetric ruthenium-catalysed hydrogen transfer reactions have been explored with significant success [381. 

Other than hydrogen transfer reactions, catalytic applications of Cp lr complexes for the deuteration of organic molecules [81-84], asymmetric Diels-Alder reactions [85, 86],... 

Moreover, the already known abihty of iridium compounds to catalyze hydrogen transfer reactions has been excellently applied in Oppenauer-type and domino-type reactions for valuable organic chemicals and further developments, including asymmetric variants to kinetic resolution of alcohols and fine chemicals, can be expected. 

Hydrogen transfer reactions have also been carried out in an asymmetric... 

The asymmetric reduction of aryl ketone can be achieved with ruthenium catalysts (Scheme 24), prepared separately or in situ by formation of [RuCl2(arene)]2 and ligand, in z-PrOH [81]. The high enantioselectivities and rate are very dependent upon the functionality of the substrate, T -arene and A -substitution of the diamino or amino alcohol ligands on ruthenium [81]. The hydrogen transfer reaction in z-PrOH is reversible, necessitating low concentrations, while extensive... 

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