Dpen catalyst

The hydrogenation of a number of aromatic ketones is shown in Figure 37.30. Noyori s very effective Ru-diphosphine-diamine technology was developed by several companies. It is not clear on which scale the processes developed by Takasago (dm-binap = 3,5-xylyl-binap) [16] and Dow/Chirotech [109-111] for the reduction of substituted acetophenones are actually applied commercially. Using the Xyl-PhanePhos-dpen catalyst, a highly efficient bench-scale process was developed for the hydrogenation of p-fluoroacetophenone (ee 98%, TON 100000, TOF 50000 IT1 at r.t., 8 bar) [109]. Ru-P-Phos (licensed to Johnson Matthey [112]) achieved ee-values >99.9% and TON up to 100000 for sev-... 

A higher enantioselectivity is obtained at a lower temperature. The enantioselectivity by 31b/(5,5)-DPEN is higher than that by ( )-10b/(5,5)-DPEN at the same temperature and pressure. The tropos 31b/(5,5)-DPEN catalyst affords (f )-l-(l-naphthyl) ethanol with 92% ee in quantitative yield (entries 3 and 4). 31b/(5,5)-DPEN is also effective for o-methylacetophenone 22a to afford (7 )-l-(l-o-methylphenyl)ethanol quantitatively with 88% ee, higher than 86% ee obtained by ( )-10b/(5,5)-DPEN (entries 5 and 6). 

Catalysts for ketone hydrogenation continue to be developed but one of the best systems is still the BINAP-DPEN catalyst first reported by Ohkuma et al. in 1995. " In this system ruthenium is combined with both a chiral diphosphine and a chiral diamine, forming an octahedral complex which gives a high degree of enantioselectivity. This stereoselectivity is considered to be a result of the synergistic effect of the chiral diphosphine and diamine ligands. 

In a related approach, Fan et al. synthesized a series of dendritic BINAP-Ru/chiral diamine ((R,R)-l,2-diphenylethylenediamine DPEN) catalysts for the asymmetric hydrogenation of various simple aryl ketones (Fig. 15) [42]. The resulting systems displayed high catalytic activity and enantioselectivity and allowed facile catalyst recycling. In the case of 1-acetonaphthone and... 

Above results inspired a kinetic study on the transfer hydrogenation as a function of pH. As in the case of [( / -C6M6)Ru(bpy)(H20)] +, and the previously mentioned Rh-catalyzed hydrogenations, Ru-Ts-DPEN catalyst showed a strong pH dependence. The rate of reduction increases sharply when pH was changed fi-om 4 to 5 in HCOOH-EtsN... 

Noyori et al. recently used ESI-MS to characterize species present in catalytically active solutions during the hydrogenation of aryl-alkyl ketones using their base-free catalyst precursors trans-[Ru((R)-tol-BINAP)((R, RJ-dpenJfHXf/ -BH ] (tol-BI-NAP = 2,2 -bis(ditolylphosphino) -1, T-binaphthyl dpen = 1,2-diphenylethylenedia-mine) in 2-propanol [9b]. Based upon ESI-MS observations, deuterium-labeling studies, kinetics, NMR observations, and other results, the authors proposed that the cationic dihydrogen complex trans-[Ru((R)-tol-BINAP)((R, R)-dpen)(H)( 2-H2)]+ is an intermediate in hydrogenations carried out in the absence of base. 

Fig. 32.32 Proposed catalytic cycle of hydrogenation of simple ketones with the TolBINAP/DPEN-Ru catalyst.

Immobilized catalysts on solid supports inherently have benefits because of their easy separation from the products and the possibility of recycling. They are also expected to be useful for combinatorial chemistry and high-throughput experimentation. The polystyrene-bound BINAP/DPEN-Ru complex (beads) in the presence of (CH3)3COK catalyzes the hydrogenation of l -acetonaphthone with an SCR of 12 300 in a 2-propanol-DMF mixture (1 1, v/v) to afford the chiral alcohol in 97% ee (Fig. 32.35) [113]. This supported complex is separable... 

Fig. 32.35 Hydrogenation of I -acetonaphthone with the polymer-bound BINAP/DPEN-Ru catalyst.

Fig. 32.50 Hydrogenation of 1-acetonaphthone with a DM-BI-PHEP/(S,S)-DPEN-Ru catalyst.

DM-BIPHEP, a conformationally flexible diphosphine, exists as an equilibrium mixture of the R and S isomers (Fig. 32.50) [141]. Addition of an equimolar amount of (S,S)-DPEN to RuCl2(dm-biphep)(dmf) forms a 3 1 mixture of (S)-DM-BIPHEP/(S,S)-DPEN-RuC12 complex and the R,SS diastereoisomer. The major S,SS complex gives a more active and enantioselective catalyst for the hydro-... 

---