(η⁶-Arene)Ru^II/Chiral SN Ligand: A Novel Bifunctional Catalyst System for Asymmetric Transfer Hydrogenation of Aromatic Ketones

Abstract

A binary catalyst system of [RuCl₂(η⁶-arene)]₂ and a protic aminothiol (SN) ligand has been found to promote hydrogen transfer between alcohols and carbonyl compounds. The chiral catalyst system with the pipecolinol-derived chiral SN ligand displays excellent stereoselectivity in the asymmetric transfer hydrogenation of aromatic ketones using HCO₂H-Et₃N. Novel unsymmetrical bis(thiolate)-bridged binuclear complex, which is relevant to the generation of catalytically active species, has been synthesized and structurally characterized.

Key words

[RuCl₂(η⁶-arene)]₂ - protic aminothiol ligand - asymmetric transfer hydrogenation - aromatic ketone - bifunctionality

References and Notes

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• 13a

  Details will be reported separately.
  

• 13b

  Preparation of ( S , S )-15e
  A mixture of [RuCl₂ (hmb)]₂ (314.5 mg, 0.470 mmol), (S)-2e˙HCl (143.1 mg, 0.931 mmol), and KOt-Bu (157.1 mg, 1.40 mmol) in CH₂Cl₂ (6 mL) was stirred at r.t. for 12 h. Removal of the solvent under reduced pressure gave a dark yellow powder, which was washed with THF and then extracted with CH₂Cl₂. The extract was concentrated in vacuo to give a red solid, which was purified by recrys-tallization from MeOH and Et₂O to give pure (S,S)-15e as red crystals (258.0 mg, 63%). ^¹H NMR (300 MHz, CD₂Cl₂, 300 K): δ = 1.81-1.90 (m, 5 H), 1.98-2.10 (m, 4 H), 2.02 (s, 18 H), 2.11 (s, 18 H), 2.02-2.32 (m, 5 H), 2.69-2.72 (m, 2 H), 2.88-2.90 (m, 1 H), 3.25-3.27 (m, 1 H), 3.81-3.83 (m, 1 H), 6.07 (br s, 1 H), 9.61 (br s, 1 H), 10.32 (br s, 1 H). ^¹³C{^¹H} NMR (75 MHz, CO₂Cl₂, 300 K): δ = 15.3, 15.6, 24.0, 26.6, 27.2, 27.6, 30.8, 45.1, 50.1, 52.8, 58.5, 75.0, 95.3, 96.0. Anal. Calcd for C₃₄H₅₇Cl₃N₂Ru₂S₂×5/2H₂O: C, 44.8; H, 6.86; N, 3.07. Found: C, 44.74; H, 6.94; N, 3.20. CCDC-717904 contains the supplementary crystallographic data
  for (S,S)-15e. These data can be obtained free of charge
  from the Cambridge Crystallographic Data Centre via
  http://www.ccdc.cam.ac.uk/data_request/cif.

• 14 Koike T. Ikariya T. Adv. Synth. Catal.  2004,  346:  37 
• 15a

  Yield 95%, based on (S)-4-phenyl-2-oxazolidinone. ^¹H NMR (300 MHz, CDCl₃, 300 K): δ = 1.21 (br s, 2 H), 2.53 (dd, J = 13.3, 9.0 Hz, 1 H), 2.68 (dd, J = 13.3, 4.2 Hz, 1 H), 3.61 (s, 2 H), 3.94 (dd, J = 9.0, 4.2 Hz, 1 H), 7.18-7.27
  (m, 10 H).

• 15b

  Yield 25%, based on (S)-4-isopropyl-2-oxazolidinone. ^¹H NMR (300 MHz, CDCl₃, 300 K):
  δ = 0.83-0.86 (m, 6 H), 1.28 (br s, 2 H), 1.54-1.65 (m, 1 H), 2.24 (dd, J = 13.6, 3.7 Hz, 1 H), 2.56-2.61 (m, 2 H), 3.69 (s, 2 H), 7.18-7.30 (m, 5 H).

• 15c

  Yield 82%, based on (S)-4-benzyl-2-oxazolidinone. ^¹H NMR (300 MHz, CDCl₃, 300 K): δ = 1.27 (br s, 2 H), 2.34 (dd, J = 13.2, 8.3 Hz, 1 H), 2.56-2.62 (m, 2 H), 2.73 (dd, J = 13.2, 5.6 Hz, 1 H), 3.04-3.12 (m, 1 H), 3.69 (s, 2 H), 7.16-7.30 (m, 10 H).

• 15d

  Yield 81%, based on N,O-carbonyl-l-prolinol.^{³d ¹}H NMR (300 MHz, CDCl₃, 300 K): δ = 1.31-1.43 (m, 1 H), 1.67-1.93 (m, 4 H), 2.49-2.53 (m, 2 H), 2.82-2.88 (m, 1 H), 2.92-3.00 (m, 1 H), 3.13-3.22 (m, 1 H), 3.74 (s, 2 H), 7.21-7.31 (m, 5 H).

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8

The rate difference between enantiomeric 1 became more significant with the catalyst system with (S)-2e. Thus, it reduced the ee value of (S)-1 (>99% ee) to 13% within 6 h but that of (R)-1 (>99% ee) did not change significantly (94%) under identical conditions.

11

In contrast with the outcome in entry 1 of Table  [¹] , (S)-1 with moderate ee (61%) was obtained from 3 in lower yield (38%) with the binary catalyst system of [RuCl₂ (hmb)]₂ and (S)-pipecolinol with under otherwise identical conditions.

12

The catalyst system of [RuCl₂ (η⁶-p-cymene)]₂ and (S)-2f˙HCl promoted the ATH of 3 to give (S)-1 with 12% ee in 31% yield and that with [RuCl₂ (η⁶-benzene)]₂ and (S)-2f˙HCl hardly promoted the ATH of 3 to give rac-1 in 4% yield under otherwise identical conditions.