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

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-d8. 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.

采用铜催化的转金属反应试剂[Cu-(Kaibene)2]I，将NHC配体（S,S）-MeNC3H2NCHPhCHPhNH2“Kaibene”转移至钌，制备出前催化剂[RuCp*-(Kaibene)-(MeCN)](PF6)（Cp* = 1,2,3,4,5-五甲基环戊二烯基），7，以高收率（两种对映异构体的混合物）实现。在相对温和的条件下（0.02摩尔%钌，0.16摩尔%KOtBu，异丙醇，50°C，25巴氢气压力），该化合物有效地催化芳基酮及一种烷基酮的氢化反应，展现出卓越的活性和产率（TOF高达48 s–1，TON高达104）。在更高的氢化压力（46巴）下，N-苯基苯乙亚胺至相应胺的催化加氢反应得以高效实现。对前手性酮的氢化导致低对映选择性（4-氯乙酰苯酮的对映选择性为35%）。利用核磁共振波谱技术观测了由7与H2和碱在THF-d8中反应生成的对映异构体氢化物RuCp*-(Kaibene)-(H) 13-R/S。互补的DFT研究指出，根据底物的不同，异裂氢分子形成13-R/S或氢化物向底物的转移可能是决定反应速率的关键步骤。实验和计算结果支持了涉及THF中Kaibene配体酰胺连接形式上异裂氢分子至氮或来自产物醇或2-丙醇溶剂的溶剂外层氧化物的机理。一个不寻常的特征是产物醇的对映选择性迅速下降，从高达60%（R）降至某些情况下的0%；这可能是由于强碱引起的THF中Kaibene配体的外消旋化，或者由于催化剂的一种对映异构体与产物（R）-醇反应导致的竞争性抑制。