Preparation of Neutral trans - cis [Ru(O₂CR)₂P₂(NN)], Cationic [Ru(O₂CR)P₂(NN)](O₂CR) and Pincer [Ru(O₂CR)(CNN)P₂] (P = PPh₃, P₂ = diphosphine) Carboxylate Complexes and their Application in the Catalytic Carbonyl Compounds Reduction

Abstract

The diacetate complexes trans-[Ru(κ 1 -OAc) 2 (PPh 3 ) 2 (NN)] (NN = ethylenediamine (en) (1), 2-(aminomethyl)pyridine (ampy) (2), 2-(aminomethyl)pyrimidine (ampyrim) (3)) have been isolated in 76−88% yield by reaction of [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] with the corresponding nitrogen ligands. The ampy-type derivatives 2 and 3 undergo isomerization to the thermodynamically most stable cationic complexes [Ru(κ 1 -OAc)(PPh 3 ) 2 (NN)]OAc (2a and 3a) and cis-[Ru(κ 1 -OAc) 2 (PPh 3 ) 2 (NN)] (2b and 3b) in methanol at RT. The trans-[Ru(κ 1 -OAc) 2 (P 2 ) 2 ] (P 2 = dppm (4), dppe (5)) compounds have been synthesized from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] by reaction with the suitable diphosphine in toluene at 95 °C. The complex cis-[Ru(κ 1 -OAc) 2 (dppm)-(ampy)]( 6) has been obtained from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] and dppm in toluene at reflux and reaction with ampy. The derivatives trans-[Ru(κ 1 -OAc) 2 P 2 (NN)] (7−16; NN = en, ampy, ampyrim, 8-aminoquinoline; P 2 = dppp, dppb, dppf, (R)-BINAP) can be easily synthesized from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] with a diphosphine and treatment with the NN ligands at RT. Alternatively these compounds have been prepared from trans-[Ru(OAc) 2 (PPh 3 ) 2 (NN)] by reaction with the diphosphine in MEK at 50 °C. The use of (R)-BINAP affords trans-[Ru(κ 1 -OAc) 2 ((R)-BINAP)(NN)] (NN = ampy (11), ampyrim (15)) isolated as single stereoisomers. Treatment of the ampy-type complexes 8−15 with methanol at RT leads to isomerization to the cationic derivatives [Ru(κ 2 -OAc)P 2 (NN)]OAc (8a−15a; NN = ampy, ampyrim; P 2 = dppp, dppb, dppf, (R)-BINAP). Similarly to 2, the dipivalate trans-[Ru(κ 1 -OPiv) 2 (PPh 3 ) 2 (ampy)] ( 18) is prepared from [Ru(κ 2 -OPiv) 2 (PPh 3 ) 2 ] (17) and ampy in CHCl 3 . The pincer acetate [Ru(κ 1 -OAc)(CNN OMe )(PPh 3 ) 2 ] (19) has been synthesized from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ] and HCNN OMe ligand in 2-propanol with NEt 3 at reflux. In addition, the dppb pincer complexes [Ru(κ 1 -OAc)(CNN)(dppb)] (CNN = AMTP (20), AMBQ Ph (21)) have been obtained from [Ru(κ 2 -OAc) 2 (PPh 3 ) 2 ], dppb, and HAMTP or HAMBQ Ph with NEt 3 , respectively. The acetate NN and pincer complexes are active in transfer hydrogenation with 2-propanol and hydrogenation with H 2 of carbonyl compounds at S/C values of up to 10000 and with TOF values of up to 160000 h −1 .

Enantioselective Cytotoxicity of Chiral Diphosphine Ruthenium(II) Complexes Against Cancer Cells

“…Chiral ruthenium complexes have been deeply investigated in the asymmetric hydrogenation [18] and transfer hydrogenation [19,20] of carbonyl compounds. Outstanding catalysts are the arene [RuCl(η 6 -arene)(TsDPEN)], [21][22][23] the diphosphine [RuCl 2 (PP)(NN)], [24][25][26][27] as well as the carboxylate [Ru(η 1 -OCOR) 2 (PP)(en)] [28] and [Ru(η 2 -OAc)(CO)(PP)(NN)]OAc [29,30] (PP = diphosphine, NN = diamine, ampy) complexes.…”

Beyond Metal-Arenes: Monocarbonyl Ruthenium(II) Catalysts for Transfer Hydrogenation Reactions in Water and in Cells

“…For complex 4, the same reaction was conducted at 80 °C in EtOH using picolinamidate (pica) as a ligand in order to afford a neutral complex by displacement of one acetate ligand. In addition, the corresponding non-carbonylic compound 2A was obtained from the diacetate analogue [Ru(η 2 -OAc) 2 (dppb)] 41 after reacting with 1,10-phenanthroline in methanol at 60 °C. All of the complexes display high solubility and stability in several media, including alcohols (MeOH and EtOH), chloroform, dichloromethane (DCM), acetone, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO).…”

“…In terms of biological applications, relevant to our study, the presence of the acetate ligand highly increases the catalysts' solubility in water. 36,41,48,49 Here, we report on the synthesis of three Ru(II) monocarbonyl compounds (Scheme 1, complexes 1−3), featuring the same bidentate phosphine 1,4-bis-(diphenylphosphino)butane (dppb) but different N ∧ N ligands, namely, 2,2′-bipyridine (bipy), 1,10-phenanthroline (phen), and pyrazino[2,3-f ][1,10]phenanthroline (pzphen) � to explore the effects of the different aromatic scaffolds on the catalytic activity of the compounds. Moreover, inspired by the aforementioned previous work on Ir(III)-arene complexes, featuring the picolinamidate (pica) ligand, 33,50 we synthesized the corresponding monocarbonyl analogue (Scheme 1, complex 4).…”

“…The new compounds are based on a Ru­(II) monocarbonyl scaffold, featuring bidentate nitrogen (N ∧ N) and diphosphine (P ∧ P) ligands, of general formula [Ru­(OAc)­CO­(dppb)­(N ∧ N)] n ( n = +1, 0; dppb = 1,4-bis­(diphenylphosphino)­butane). Monocarbonyl ruthenium complexes have attracted a great deal of attention in homogeneous catalysis due to their ability to promote several transformations, including in the transfer hydrogenation and hydrogenation of a number of carbonyl compounds. − However, to the best of our knowledge, they have never been tested in TH reactions with the NAD + /NADH couple. Recent studies also showed that similar compounds are indeed cytotoxic in cancer cells. − …”

Beyond Metal-Arenes: Monocarbonyl Ruthenium(II) Catalysts for Transfer Hydrogenation Reactions in Cancer Cells

“…Within this framework, we decided to explore a different family of TH organometallic catalysts based on a Ru(II) monocarbonyl scaffold featuring bidentate nitrogen (N^N) and diphosphine (P^P) ligands, of general formula [Ru(OAc)CO(dppb)(N^N)] n (n = +1, 0; dppb = 1,4-bis(diphenylphosphino)butane). Monocarbonyl ruthenium complexes have attracted a great deal of attention in homogeneous catalysis due to their ability to promote several transformations, including in the transfer hydrogenation and hydrogenation of a number of carbonyl compounds [27][28][29][30][31][32] . However, to the best of our knowledge, they have never been tested in TH reactions with the NAD + /NADH couple.…”