Half-Sandwich Ruthenium Catalyst Bearing an Enantiopure Primary Amine Tethered to an N-Heterocyclic Carbene for Ketone Hydrogenation

Abstract

By using a copper transmetalation reagent [Cu­(Kaibene)2]­I, the NHC ligand (S,S)-MeNC3H2NCHPhCHPhNH2 “Kaibene” was transferred to ruthenium to make a precatalyst [RuCp*­(Kaibene)­(MeCN)]­(PF6) (Cp* = 1,2,3,4,5-pentamethyl­cyclopenta­dienyl), 7, in high yield as a mixture of two diastereomers. Under relatively mild conditions (0.02 mol % Ru, 0.16 mol % KOtBu, iPrOH, 50 °C, 25 bar of H2), this compound catalyzes the hydrogenation of aryl ketones and one alkyl ketone effectively with excellent activity and productivity (TOF up to 48 s–1, TON up to 104). At higher hydrogenation pressure (46 bar), the catalytic hydrogenation of N-phenyl-benzylimine to the corresponding amine is efficiently achieved. The hydrogenation of prochiral ketones resulted in low ee (35% for 4-chloroacetophenone). NMR spectroscopy was used to observe diastereomeric hydrides RuCp*­(Kaibene)­(H) 13- R/S that were generated by reaction of 7 with H2 and base in THF-d 8. Complementary DFT studies suggest that either the heterolytic splitting of dihydrogen to form 13- R/S or the hydride transfer to the substrate can be rate-determining depending on the substrate. Experimental and computational results support mechanisms that involve the heterolytic splitting of dihydrogen to the nitrogen of the amide-ligated form of Kaibene in THF or the heterolytic splitting to an outer-sphere alkoxide derived from the product alcohol or 2-PrOH solvent. An unusual feature is the rapid drop in ee of the product alcohol from as high as 60% (R) to 0% in some cases; this might be due to racemization of the Kaibene ligand in THF caused by the strong base or competitive inhibition of one diastereomer of the catalyst by reaction with the product (R)-alcohol.

Recent Advances in Catalysis Involving Bidentate N-Heterocyclic Carbene Ligands

“…An outstanding case among this particular class of ligands is the chiral proligand 81 [ 31 ], depicted in Figure 6 along with two ruthenium complexes ( 82 , 83 ) [ 140 ].…”

Electronic Effects on Chiral NHC–Transition-Metal Catalysis

“…For example in 2016, the Morris group have reported the use of chiral NHCs containing a primary amine as a chelator. [38][39][40] The use of such ligands was examined with several metal centers, such as Ru, [38][39][40] Ir, [38][39][40] Ag, 38,39 and Cu, 38,39 as well as on a number of catalytic reactions like the hydrogenation of acetophenone 38 and N-phenylbenzylimine 40 and ketones in general. 39 These catalysts were often able to achieve high yields and showed promising ability towards asymmetric catalysis.…”

Current advances on ruthenium(II) N-heterocyclic carbenes in hydrogenation reactions

“…17. Ruthenium(II) half-sandwich complex applied for the asymmetric HY of ketones [104]. A dependence of the product formation on the steric demand of the wingtip substituent can be observed (Table 17).…”