Walter Baratta

The pincer complexes [MX(CNN)(PP)] (M = Ru, Os; X = Cl, OTf; HCNN = 1-(6-arylpyridin-2-yl)methanamine; PP = diphosphine) have proven to efficiently catalyze both racemization and deuteration of alcohols in the presence of a base. Chiral alcohols have been racemized at 30–50 °C using 1 mol% of Ru or Os pincer complexes and 5 mol% of KOtBu in 2-propanol. Primary and secondary alcohols are efficiently deuterated at the α position, with respect to the OH group, using 2-propanol-d₈ as solvent with Ru or Os pincer complexes and KOtBu at 30–50 °C. For secondary alcohols incorporation of deuterium at the β position has also been observed. In 2-propanol-d₈ the pincer complexes catalyze the simultaneous deuteration and racemization of (S)-1-phenylethanol, the two processes being strictly correlated. For both reactions much the same activity has been observed with the Ru and Os complexes. The pincer complexes display a superior activity with respect to the related compounds [MCl₂(NN)(PP)] (NN = bidentate amine or pyridine ligand). The synthesis of the new complexes [MCl(CNN)(PP)] (M = Ru, 2, 4 and Os, 6, 7; PP = dppb, dppf) and [Ru(OTf)(CNN)(dppb)] (3) is also reported.

The ruthenium and osmium complexes [MCl₂(diphosphane)(L)] (M=Ru, Os; L=bidentate amino ligand) and [MCl(CNN)(dppb)] (CNN=pincer ligand; dppb=1,4‐bis‐ (diphenylphosphino)butane), containing the N–H moiety, have been found to catalyze the acceptorless dehydrogenation of alcohols in tBuOH and in the presence of KOtBu. The compounds trans‐[MCl₂(dppf)(en)] (M=Ru 7, Os 13; dppf=1,1′‐bis(diphenylphosphino)ferrocene; en=ethylenediamine) display very high activity and different substrates, including cyclic and linear alcohols, are efficiently oxidized to ketones by using 0.8–0.04 mol % of catalyst. The effect of the base and the comparison of the catalytic activity of the Ru versus Os complexes are reported. The ruthenium complex 7 generally leads to a faster conversion into ketones with respect to the osmium complex 13, which displays better activity in the dehydrogenation of 5‐en‐3β‐hydroxy steroids. The synthesis of new Ru and Os complexes [MCl₂(PP)(L)] (PP=dppb, dppf; L=(±)‐trans‐1,2‐diaminocyclohexane, 2‐(aminomethyl)pyridine, and 2‐aminoethanol) of trans and cis configuration is also reported.

Chiral orthometalated osmium complexes [OsCl(CN′N)(PP)] {PP = (S,R)‐Josiphos type diphosphane} based on 2‐aminomethylbenzo[h]quinoline ligands (HCN′N) were prepared by reaction of [OsCl₂(PPh₃)₃] with a Josiphos diphosphane and a HCN′N ligand in the presence of NEt₃. Ruthenium and osmium complexes [MX(CN′N)(PP)] {M = Ru, Os; X = Cl, OCH(p‐C₆H₄F)₂; PP = dppb, (S,R)‐Josiphos}, in the presence of KOtBu, efficiently catalyze the chemoselective hydrogenation (H₂ = 5 atm) of aromatic and aliphatic ketones to secondary alcohols in methanol or methanol/ethanol mixtures, when a S/C ratio of 10000–50000 is used. With use of these chiral phosphanes, alkyl aryl ketones have been reduced with ee values up to 99 % and turnover frequencies (TOFs) up to 5.6 × 10⁴ h^–1.

The osmium complexes trans‐[OsCl₂(dppf)(diamine)] (dppf: 1,1′‐bis(diphenylphosphino)ferrocene; diamine: ethylenediamine in 3, propylenediamine in 4) were prepared by the reaction of [OsCl₂(PPh₃)₃] (1) with the ferrocenyl diphosphane, dppf and the corresponding diamine in dichloromethane. The reaction of derivative 3 with NaOCH₂CF₃ in toluene afforded the alkoxide cis‐[Os(OCH₂CF₃)₂(dppf)(ethylenediamine)] (5). The novel precursor [Os₂Cl₄(P(m‐tolyl)₃)₅] (2) allows the synthesis of the chiral complexes trans‐[OsCl₂(diphosphane)(1,2‐diamine)] (6–9; diphosphane: (R)‐[6,6′‐dimethoxy(1,1′‐biphenyl)‐2,2′‐diyl]bis[1,1‐bis(3,5‐dimethylphenyl)phosphane] (xylMeObiphep) or (R)‐(1,1′‐binaphthalene)‐2,2′‐diylbis[1,1‐bis(3,5‐dimethylphenyl)phosphane] (xylbinap); diamine=(R,R)‐1,2‐diphenylethylenediamine (dpen) or (R,R)‐1,2‐diaminocyclohexane (dach)), obtained by the treatment of 2 with the diphosphane and the 1,2‐diamine in toluene at reflux temperature. Compounds 3–5 in ethanol and in the presence of NaOEt catalyze the reduction of methyl aryl, dialkyl, and diaryl ketones and aldehydes with H₂ at low pressure (5 atm), with substrate/catalyst (S/C) ratios of 10 000–200 000 and achieving turnover frequencies (TOFs) of up to 3.0×10⁵ h⁻¹ at 70 °C. By employment of the chiral compounds 6–9, different ketones, including alkyl aryl, bulky tert‐butyl, and cyclic ketones, have successfully been hydrogenated with enantioselectivities up to 99 % and with S/C ratios of 5000–100 000 and TOFs of up to 4.1×10⁴ h⁻¹ at 60 °C.

Chiral pincer ruthenium complexes of formula [RuCl(CNN)(Josiphos)] (2–7; Josiphos=1‐[1‐(dicyclohexylphosphano)ethyl]‐2‐(diarylphosphano)ferrocene) have been prepared by treating [RuCl₂(PPh₃)₃] with (S,R)‐Josiphos diphosphanes and 1‐substituted‐1‐(6‐arylpyridin‐2‐yl)methanamines (HCNN; substituent=H (1 a), Me (1 b), and tBu (1 c)) with NEt₃. By using 1 b and 1 c as a racemic mixture, complexes 4–7 were obtained through a diastereoselective synthesis promoted by acetic acid. These pincer complexes, which display correctly matched chiral PP and CNN ligands, are remarkably active catalysts for the asymmetric reduction of alkyl aryl ketones in basic alcohol media by both transfer hydrogenation (TH) and hydrogenation (HY), achieving enantioselectivities of up to 99 %. In 2‐propanol, the enantioselective TH of ketones was accomplished by using a catalyst loading as low as 0.002 mol % and afforded a turnover frequency (TOF) of 10⁵–10⁶ h⁻¹ (60 and 82 °C). In methanol/ethanol mixtures, the CNN pincer complexes catalyzed the asymmetric HY of ketones with H₂ (5 atm) at 0.01 mol % relative to the complex with a TOF of ≈10⁴ h⁻¹ at 40 °C.

New benzo[h]quinoline ligands (HCN′N) containing a CHRNH₂ (R=H (a), Me (b), tBu (c)) function in the 2‐position were prepared starting from benzo[h]quinoline N‐oxide (in the case of ligand a) and 2‐chlorobenzo[h]quinoline (for ligands b and c). These compounds were used to prepare ruthenium and osmium complexes, which are excellent catalysts for the transfer hydrogenation (TH) of ketones. The reaction of a with [RuCl₂(PPh₃)₃] in 2‐propanol at reflux afforded the terdentate CN′N complex [RuCl(CN′N)(PPh₃)₂] (1), whereas the complexes [RuCl(CN′N)(dppb)] (2–4; dppb=Ph₂P(CH₂)₄PPh₂) were obtained from [RuCl₂(PPh₃)(dppb)] with a–c, respectively. Employment of (R,S)‐Josiphos, (S,R)‐Josiphos*, (S,S)‐Skewphos, and (S)‐MeO‐Biphep in combination with [RuCl₂(PPh₃)₃] and ligand a gave the chiral derivatives [RuCl(CN′N)(PP)] (5–8). The osmium complex [OsCl(CN′N)(dppb)] (12) was prepared by treatment of [OsCl₂(PPh₃)₃] with dppb and ligand a. Reaction of the chloride 2 and 12 with NaOiPr in 2‐propanol/toluene afforded the hydride complexes [MH(CN′N)(dppb)] (M=Ru 10, Os 14), through elimination of acetone from [M(OiPr)(CN′N)(dppb)] (M=Ru 9, Os 13). The species 9 and 13 easily reacted with 4,4′‐difluorobenzophenone, via 10 and 14, respectively, affording the corresponding isolable alkoxides [M(OR)(CN′N)(dppb)] (M=Ru 11, Os 15). The complexes [MX(CN′N)(P₂)] (1–15) (M=Ru, Os; X=Cl, H, OR; P=PPh₃ and P₂=diphosphane) are efficient catalysts for the TH of carbonyl compounds with 2‐propanol in the presence of NaOiPr (2 mol %). Turnover frequency (TOF) values up to 1.8×10⁶ h⁻¹ have been achieved using 0.02–0.001 mol % of catalyst. Much the same activity has been observed for the RuCl, H, OR, and the OsCl derivatives, whereas the OsH and OsOR derivatives display significantly lower activity on account of their high oxygen sensitivity. The chiral Ru complexes 5–8 catalyze the asymmetric TH of methyl–aryl ketones with TOF ≈10⁵ h⁻¹ at 60 °C, up to 97 % enatiomeric excess (ee) and remarkably high productivity (0.005 mol % catalyst loading). High catalytic activity (TOF up to 2.2×10⁵ h⁻¹) and enantioselectivity (up to 98 % ee) have also been achieved with the in‐situ‐generated catalysts prepared from [MCl₂(PPh₃)₃], (S,R)‐Josiphos or (S,R)‐Josiphos*, and the benzo[h]quinoline ligands a–c.

This Microreview focuses on the development of novel ruthenium complexes displaying high performance in the catalytic asymmetric transfer hydrogenation of ketones with 2‐propanol, providing this procedure alternative to the hydrogenation with dihydrogen. The key role is played by 1‐(pyridin‐2‐yl)methanamine (Pyme) type ligands which in combination with appropriate phosphanes afforded ruthenium systems of unprecedented high catalytic activity and productivity for the reduction of ketones and aldehydes. For the pincer CNN complexes a mixed inner‐outer sphere mechanism involving Ru‐hydride and Ru‐alkoxide species is proposed. The excellent properties of these complexes are expected to have implications for the design of a new generation of catalysts.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The reaction of [RuCl(CNN)(dppb)] (1; HCNN=6‐(4‐methylphenyl)‐2‐pyridylmethylamine) with NaOiPr in 2‐propanol/C₆D₆ affords the alcohol adduct alkoxide [Ru(OiPr)(CNN)(dppb)]⋅n iPrOH (5), containing the RuNH₂ linkage. The alkoxide [Ru(OiPr)(CNN)(dppb)] (4) is formed by treatment of the hydride [Ru(H)(CNN)(dppb)] (2) with acetone in C₆D₆. Complex 5 in 2‐propanol/C₆D₆ equilibrates quickly with hydride 2 and acetone with an exchange rate of (5.4±0.2) s⁻¹ at 25 °C, higher than that found between 4 and 2 ((2.9±0.4) s⁻¹). This fast process, involving a β‐hydrogen elimination versus ketone insertion into the RuH bond, occurs within a hydrogen‐bonding network favored by the RuNH₂ motif. The cationic alcohol complex [Ru(CNN)(dppb)(iPrOH)](BAr^f₄) (6; Ar^f=3,5‐C₆H₃(CF₃)₂), obtained from 1, Na[BAr^f₄], and 2‐propanol, reacts with NaOiPr to afford 5. Complex 5 reacts with either 4,4′‐difluorobenzophenone through hydride 2 or with 4,4′‐difluorobenzhydrol through protonation, affording the alkoxide [Ru{OCH(4‐C₆H₄F)₂}(CNN)(dppb)] (7) in 90 and 85 % yield of the isolated product. The chiral CNN–ruthenium compound [RuCl(CNN){(S,S)‐Skewphos}] (8), obtained by the reaction of [RuCl₂(PPh₃)₃] with (S,S)‐Skewphos and orthometalation of HCNN in the presence of NEt₃, is a highly active catalyst for the enantioselective transfer hydrogenation of methylaryl ketones (turnover frequencies (TOFs) of up to 1.4×10⁶ h⁻¹ at reflux were obtained) with up to 89 % ee. Also the ketone CF₃CO(4‐C₆H₄F), containing the strong electron‐withdrawing CF₃ group, is reduced to the R alcohol with 64 % ee and a TOF of 1.5×10⁴ h⁻¹. The chiral alkoxide [Ru(OiPr)(CNN){(S,S)‐Skewphos}]⋅n iPrOH (9), obtained from 8 and NaOiPr in the presence of 2‐propanol, reacts with CF₃CO(4‐C₆H₄F) to afford a mixture of the diastereomer alkoxides [Ru{OCH(CF₃)(4‐C₆H₄F)}(CNN){(S,S)‐Skewphos}] (10/11; 74 % yield) with 67 % de. This value is very close to the enantiomeric excess of the alcohol (R)‐CF₃CH(OH)(4‐C₆H₄F) formed in catalysis, thus suggesting that diastereoisomeric alkoxides with the RuNH₂ linkage are key species in the catalytic asymmetric transfer hydrogenation reaction.