CATHy reducing system

Fig. 7 Large scale applications of the CATHy reducing system...

Rather surprisingly alcohols are poor at reducing imines, yet TEAF works well. During our studies we rationalized that the TEAF system was sufficiently acidic (pH approximately 4) to protonate the imine (pK l approximately 6) and that it was an iminium that was reduced to an ammonium salt [14]. When an iminium was used in the I PA system, it was reduced albeit with a low rate and moderate enan-tioselectivity. Quaternary iminium salts were also reduced to tertiary amines. Hydrogen will not reduce ketones or imines using the CATHy catalysts, but hydrides such as sodium borohydride have been shown to work. 

A recent development is the transfer hydrogenation of heterocyclic systems such as pyrrole, pyridinium, and quinoline systems. Whilst the yields and enan-tioselectivities are modest at the moment, further development may improve this. For example, 1-methyl-isoquinoline has been reduced to the tetrahydro species and 1-picoline has been reduced to 1-methylpiperidine. Hydrogenation of alkenes has been reported [16], but in the CATHy -catalyzed reaction alkene reduction has only been observed after extended reaction times. Whilst heterogeneous transfer hydrogenation of nitro groups is well known, homogeneous systems do not reduce these groups. 

The CATHy catalysts are best used below 40 °C, above this temperature we have observed signs of decomposition. In the I PA system, preventing the back-re-action depends on how efficiently acetone is distilled. Normally this would be best done at around 80 °C, the boiling point of isopropanol, but an optimal performance of the catalyst requires ambient temperature or less, and reduced pressure. Whilst acetone can be fractionally distilled, it is simpler to distil the mixture with isopropanol and to maintain constant volume by continuously charging with fresh solvent. In the TEAF system the reaction is normally operated at ambient temperature. Operating at lower temperatures can improve the enantiomeric excess slightly but gives lower rates, for example with 4-fluoroacetophenone the results described in Tab. 3 were achieved. 

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