Santo Magnolia

New Benzo[h]quinoline‐Based Ligands and their Pincer Ru and Os Complexes for Efficient Catalytic Transfer Hydrogenation of Carbonyl Compounds

New benzo[h]quinoline ligands (HCNN) 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 CNN complex [RuCl(CNN)(PPh3)2] (1), whereas the complexes [RuCl(CNN)(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(CNN)(PP)] (5-8). The osmium complex [OsCl(CNN)(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(CNN)(dppb)] (M=Ru 10, Os 14), through elimination of acetone from [M(OiPr)(CNN)(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)(CNN)(dppb)] (M=Ru 11, Os 15). The complexes [MX(CNN)(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 1.8x10(6) 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 approximately 10(5) h(-1) at 60 degrees C, up to 97 % enatiomeric excess (ee) and remarkably high productivity (0.005 mol % catalyst loading). High catalytic activity (TOF up to 2.2x10(5) 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.

Highly Productive CNN Pincer Ruthenium Catalysts for the Asymmetric Reduction of Alkyl Aryl Ketones

Chiral pincer ruthenium complexes of formula [RuCl(CNN)(Josiphos)] (2-7; Josiphos = 1-[1-(dicyclohexylphosphano)ethyl]-2-(diarylphosphano)ferrocene) have been prepared by treating [RuCl(2)(PPh(3))(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 NEt(3). 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 10(5)-10(6) h(-1) (60 and 82 degrees C). In methanol/ethanol mixtures, the CNN pincer complexes catalyzed the asymmetric HY of ketones with H(2) (5 atm) at 0.01 mol % relative to the complex with a TOF of approximately 10(4) h(-1) at 40 degrees C.

Osmium Pyme Complexes for Fast Hydrogenation and Asymmetric Transfer Hydrogenation of Ketones

The osmium compound trans,cis-[OsCl2(PPh3)2(Pyme)] (1) (Pyme=1-(pyridin-2-yl)methanamine), obtained from [OsCl2(PPh3)3] and Pyme, thermally isomerizes to cis,cis-[OsCl2(PPh3)(2)(Pyme)] (2) in mesitylene at 150 degrees C. Reaction of [OsCl2(PPh3)3] with Ph2P(CH2)(4)PPh2 (dppb) and Pyme in mesitylene (150 degrees C, 4 h) leads to a mixture of trans-[OsCl2(dppb)(Pyme)] (3) and cis-[OsCl2(dppb)(Pyme)] (4) in about an 1:3 molar ratio. The complex trans-[OsCl2(dppb)(Pyet)] (5) (Pyet=2-(pyridin-2-yl)ethanamine) is formed by reaction of [OsCl2(PPh3)3] with dppb and Pyet in toluene at reflux. Compounds 1, 2, 5 and the mixture of isomers 3/4 efficiently catalyze the transfer hydrogenation (TH) of different ketones in refluxing 2-propanol and in the presence of NaOiPr (2.0 mol %). Interestingly, 3/4 has been proven to reduce different ketones (even bulky) by means of TH with a remarkably high turnover frequency (TOF up to 5.7 x 10(5) h(-1)) and at very low loading (0.05-0.001 mol %). The system 3/4 also efficiently catalyzes the hydrogenation of many ketones (H2, 5.0 atm) in ethanol with KOtBu (2.0 mol %) at 70 degrees C (TOF up to 1.5 x 10(4) h(-1)). The in-situ-generated catalysts prepared by the reaction of [OsCl2(PPh3)3] with Josiphos diphosphanes and (+/-)-1-alkyl-substituted Pyme ligands, promote the enantioselective TH of different ketones with 91-96 % ee (ee=enantiomeric excess) and with a TOF of up to 1.9 x 10(4) h(-1) at 60 degrees C.

Chiral and Nonchiral [OsX2(diphosphane)(diamine)] (X: Cl, OCH2CF3) Complexes for Fast Hydrogenation of Carbonyl Compounds

The osmium complexes trans-[OsCl(2)(dppf)(diamine)] (dppf: 1,1-bis(diphenylphosphino)ferrocene; diamine: ethylenediamine in 3, propylenediamine in 4) were prepared by the reaction of [OsCl(2)(PPh(3))(3)] (1) with the ferrocenyl diphosphane, dppf and the corresponding diamine in dichloromethane. The reaction of derivative 3 with NaOCH(2)CF(3) in toluene afforded the alkoxide cis-[Os(OCH(2)CF(3))(2)(dppf)(ethylenediamine)] (5). The novel precursor [Os(2)Cl(4)(P(m-tolyl)(3))(5)] (2) allows the synthesis of the chiral complexes trans-[OsCl(2)(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 H(2) 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 x 10(5) h(-1) at 70 degrees 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 x 10(4) h(-1) at 60 degrees C.

CNN Pincer Ruthenium Catalysts for Hydrogenation and Transfer Hydrogenation of Ketones: Experimental and Computational Studies

Reaction of [RuCl(CNN)(dppb)] (1-Cl) (HCNN=2-aminomethyl-6-(4-methylphenyl)pyridine; dppb=Ph2 P(CH2 )4 PPh2 ) with NaOCH2 CF3 leads to the amine-alkoxide [Ru(CNN)(OCH2 CF3 )(dppb)] (1-OCH2 CF3 ), whose neutron diffraction study reveals a short RuO⋅⋅⋅HN bond length. Treatment of 1-Cl with NaOEt and EtOH affords the alkoxide [Ru(CNN)(OEt)(dppb)]⋅(EtOH)n (1-OEt⋅nu2009EtOH), which equilibrates with the hydride [RuH(CNN)(dppb)] (1-H) and acetaldehyde. Compound 1-OEt⋅nu2009EtOH reacts reversibly with H2 leading to 1-H and EtOH through dihydrogen splitting. NMR spectroscopic studies on 1-OEt⋅nu2009EtOH and 1-H reveal hydrogen bond interactions and exchange processes. The chloride 1-Cl catalyzes the hydrogenation (5 atm of H2 ) of ketones to alcohols (turnover frequency (TOF) up to 6.5×10(4) h(-1) , 40u2009°C). DFT calculations were performed on the reaction of [RuH(CNN)(dmpb)] (2-H) (HCNN=2-aminomethyl-6-(phenyl)pyridine; dmpb=Me2 P(CH2 )4 PMe2 ) with acetone and with one molecule of 2-propanol, in alcohol, with the alkoxide complex being the most stable species. In the first step, the Ru-hydride transfers one hydrogen atom to the carbon of the ketone, whereas the second hydrogen transfer from NH2 is mediated by the alcohol and leads to the key amide intermediate. Regeneration of the hydride complex may occur by reaction with 2-propanol or with H2 ; both pathways have low barriers and are alcohol assisted.