Biomimetic transfer hydrogenation

Scheme 4.8 Biomimetic transfer hydrogenation of ketones with iron porphyrin catalysts.

We thought to start with the metal-free biomimetic transfer hydrogenation of a,(-)-unsaturated aldehydes as a model reaction which has been earlier discovered in our laboratory and independently in that of MacMillan et al. (Scheme 24). We have prepared a large number of ammonium salts as crystalline solids by mixing different primary and secondary amines with a chiral phosphoric acid. In particular, the ammonium salts of sterically hindered chiral phosphoric acids could catalyze... 

A biomimetic transfer hydrogenation [168] approach, which employs a Hantzsch ester (44a) as an nicotinamide adenine dinucleotide plus hydrogen (NADH) model [169] thus has been independently reported by Rueping, List, and MacMillan. 

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. 

Biomimetic Reductions Amino Acid Dehydrogenases as the Role Model for the Brpnsted Acid Catalyzed Transfer Hydrogenation... 

Based on the above activation mechanism we wondered whether it would be possible to develop a biomimetic, organocatalytic reductive amination or transfer hydrogenation of ketimines. We reasoned that the activation of the imine by catalytic protonation through the Brpnsted acid should enable the hydrogen transfer from a suitable NADH mimic to yield the corresponding amine (Fig. 2). Hence, initial experiments focused on the examination of various Brpnsted acids in combination with different hydride sources (Rueping et al. 2005a). 

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... 

Polborn, K. Severin, K. Biomimetic catalysis with immobilised organometallic ruthenium complexes substrate- and regioselective transfer hydrogenation of ketones. Chem. Eur. J. 2000, 5, 4604-4611. 

Soc., 130, 13862-13863 (g) You, S.-L (2007) Recent developments in asymmetric transfer hydrogenation with Hantzsch esters a biomimetic approach. Chem. 

Many other important theoretical concepts of paramount importance for biomimetic photochemistry are still in their infancy. This includes the strategies to mediate and accelerate proton-coupled single and multiple electron transfer catalysis (171-173), and the fundamental aspects of catalytic hydride transfer and hydrogen tunneling processes (174—176) among several others. 

The radical cations of diene systems in cyclic molecules are also capable of reaction as demonstrated by Demnth, Roth and their coworkers. They have studied the influence of phase on the photochemical reactivity of some naturally occurring dienes. Thns the irradiation of the diene 10 in homogeneous solution (acetonitrile/water) in the presence of an electron-accepting sensitizer such as cyanonaphthalene (CN) or DCB brings about fraws,cw-isomerization only. However, when the electron transfer reaction is carried out in the presence of sodinm dodecyl sulphate, transannular hydrogen abstraction reactions yield the two prodncts 11 and 12. Similar reactivity is observed with frans-geranyl acetate 13 and all-trawi-famesyl acetate 14. The authors report that these cyclizations are the flrst examples of biomimetic processes brought about under SET conditions. 

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