Hydrogenation versus Transfer Hydrogenation of Ketones: Two Established Ruthenium Systems Catalyze Both

Abstract

The established standard ketone hydrogenation (abbreviated HY herein) precatalyst [Ru(Cl)(2)((S)-tolbinap)[(S,S)-dpen]] ((S),(S,S)-1) has turned out also to be a precatalyst for ketone transfer hydrogenation (abbreviated TRHY herein) as tested on the substrate acetophenone (3) in iPrOH under standard conditions (45 degrees C, 45 bar H(2) or Ar at atmospheric pressure). HY works at a substrate catalyst ratio (s:c) of up to 10(6) and TRHY at s:c<10(4). Both produce (R)-1-phenylethan-1-ol ((R)-4), but the ee in HY are much higher (78-83 %) than in TRHY (4-62 %). In both modes, iPrOK is needed to generate the active catalysts, and the more there is (1-4500 equiv), the faster the catalytic reactions. The ee is about constant in HY and diminishes in TRHY as more iPrOK is added. The ketone TRHY precatalyst [Ru(Cl)(2)((S,S)-cyP(2)(NH)(2))] ((S,S)-2), established at s:c=200, has also turned out to be a ketone HY precatalyst at up to s:c=10(6), again as tested on 3 in iPrOH under standard conditions. The enantioselectivity is opposite in the two modes and only high in TRHY: with (S,S)-2, one obtains (R)-4 in up to 98 % ee in TRHY as reported and (S)-4 in 20-25 % ee in HY. iPrOK is again required to generate the active catalysts in both modes, and again, the more there is, the faster the catalytic reactions. The ee in TRHY are only high when 0.5-1 equivalents iPrOK are used and diminish when more is added, while the (low) ee is again about constant in HY as more iPrOK is added (0-4500 equiv). The new [Ru(H)(Cl)((S,S)-cyP(2)(NH)(2))] isomers (S,S)-9 A and (S,S)-9 B (mixture, exact structures unknown) are also precatalysts for the TRHY and HY of 3 under the same conditions, and (R)-4 is again produced in TRHY and (S)-4 in HY, but the lower ee shows that in TRHY (S,S)-9 A/(S,S)-9 B do not lead to the same catalysts as (S,S)-2. In contrast, the ee are in accord with (S,S)-9 A/(S,S)-9 B leading to the same catalysts as (S,S)-2 in HY. The kinetic rate law for the HY of 3 in iPrOH and in benzene using (S,S)-9 A/(S,S)-9 B/iPrOK or (S,S)-9 A/(S,S)-9 B/tBuOK is consistent with a fast, reversible addition of 3 to a five-coordinate amidohydride (S,S)-11 to give an (S,S)-11-substrate complex, in competition with the rate-determining addition of H(2) to (S,S)-11 to give a dihydride [Ru(H)(2)((S,S)-cyP(2)(NH)(2))] (S,S)-10, which in turn reacts rapidly with 3 to generate (S)-4 and (S,S)-11. The established achiral ketone TRHY precatalyst [Ru(Cl)(2)(ethP(2)(NH)(2))] (12) has turned out to be also a powerful precatalyst for the HY of 3 in iPrOH at s:c=10(6) and of some other substrates. Response to the presence of iPrOK is as before, except that 12 already functions well without it at up to s:c=10(6).

Transfer Hydrogenation of Ketones and Activated Olefins Using Chelating NHC Ruthenium Complexes

“…Despite the conceptual analogy of these two hydrogenation processes, only few systems are known that exhibit such dual activity. [8] Figure 1. Chelating NHC ruthenium complexes 1-4 and monodentate carbene ruthenium complex 5.…”

Ir(III) complexes of diamine ligands for asymmetric ketone hydrogenation

“…2-Methylacetophenone was selected for study because it had given particularly promising results in preliminary results, and because orthosubstituted substrates can be challenging substrates to reduce in high ee. Of the ligands tested, the best results were obtained using those with relatively unhindered aromatic rings containing electron withdrawing groups (entries 3,4,6,12,13,15). With the exception of ligand 9l, diamines containing substituents at the ortho-position(s) gave lower asymmetric inductions (entries 7-9), and those with two ortho-substituents were particularly poor, possibly for steric reasons.…”

“…Relatively few organometallic complexes derived from amine ligands have been reported to be effective at the control of asymmetric hydrogenation reactions, [1][2][3][4][5][6][7][8][9][10] particularly in comparison to the large numbers of diphosphine 11,12 and mixed amine/phosphine 13,14 ligands which have been reported.…”

Synthesis of Ruthenium Hydride Complexes Containing beta-Aminophosphine Ligands Derived from Amino Acids and their use in the H2-Hydrogenation of Ketones and Imines

“…Hydrogenation catalyst precursors with bidentate ligands such as RuCl 2 (binap)(diamine), [1,2,15] RuH(Cl)(binap)(diamine) [3] and RuH(BH 4 )(binap)(diamine) [16] and hydrogenation catalysts Ru(H) 2 (binap)(diamine) [4,17] are known but they do not contain an aminophosphine ligand. Ruthenium precatalysts with tetradentate Ph 2 P(C 6 H 4 )CH 2 NH-Q-NHCH 2 (C 6 H 4 )PPh 2 ligands, where Q is linking group, have also been reported for H 2 -hydrogenation [18] and transfer hydrogenation [18,19] of ketones.…”