Highly Efficient Catalyst Systems Using Iron Complexes with a Tetradentate PNNP Ligand for the Asymmetric Hydrogenation of Polar Bonds

Abstract

Iron competes with pricey ruthenium: The first catalyst systems using iron complexes for asymmetric H2 hydrogenation at 50 °C and asymmetric transfer hydrogenation at room temperature has been discovered. The transfer hydrogenation activity is similar to that of the best ruthenium catalyst. Surprisingly, the precatalysts have a tetradentate diiminodiphosphine ligand which has no NH functionality.

Asymmetric catalysis using iron complexes – ‘Ruthenium Lite’?

“…At the time of writing this review, the full mechanistic details of the reaction had not been established. It was not clear, in the case of asymmetric transfer hydrogenation, 15 whether the C=N bonds in the ligands were reduced to single bonds in the same way that they are speculated to be in the pressure hydrogenation reactions described earlier, with the subsequent mechanistic implications. The reaction is however a very practical one, with the iron catalysts exhibiting higher 20 TOF values than have been measured for the more established ruthenium-based transfer hydrogenation catalysts.…”

“…[1][2][3][4][5][6][7][8][9][10][11] Several excellent reviews have been published which describe the key findings and many of the non asymmetric precedents for the catalysts in this review. Here the focus will be on recent developments 15 in asymmetric reactions, although some non-asymmetric reactions will be discussed where they serve to place new findings into context.…”

“…Should this be the case, then the mechanism may resemble that commonly associated with the closely-related ruthenium 5 complexes (Figure 2), 16 in which hydrogen is transferred to substrate through a concerted, 6-membered ring mechanism, the well-defined nature of which contributes to the high level of enantiocontrol in the reduction. The enantiomerically-pure complexes 7 and 8 were prepared and characterised by X-ray crystallography, which revealed that the substituents on the bridging ethylene group were 15 axially positioned, possibly to avoid unfavourable steric clashes. This appears to be detrimental to activity, since only 3-4% ketone reduction was observed with these complexes after 18-24h reduction times under 25 bar hydrogen at 50 o C (225/1 S/C), although 1 gave a product of 61% ee.…”

“…17 The preformed and well-characterised Fe(II)/tetradentate 'PNNP' complex 2 described by Morris et al also works well 50 in this application, as does the related complex 3. In the earliest report, 15 hydrogen transfer from isopropanol to a series of substrates was successfully achieved using only 0.5 mol% of 2 ( Figure 7). At 22 o C, and in less than one hour, acetophenone was reduced in 95% conversion and 33% ee, 55 with a preference for the S enantiomer.…”

“…Asymmetric transfer hydrogenations of ketones using 2. 15 Catalyst 2 was also capable of the reduction of C=N bonds, with two examples reported. In the case of the benzaldehyde-5 derived imine PhCH=NPh, 100% conversion was achieved in 17h, however PhCMe=NPh, derived from acetophenone, was reduced in less than 5% conversion after the same reaction time.…”