Role of the NH₂ Functionality and Solvent in Terdentate CNN Alkoxide Ruthenium Complexes for the Fast Transfer Hydrogenation of Ketones in 2‐Propanol

Abstract

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 degrees C, higher than that found between 4 and 2 ((2.9+/-0.4) s(-1)). This fast process, involving a beta-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(f)4) (6; Ar(f)=3,5-C6H3(CF3)2), obtained from 1, Na[BAr(f)4], 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 x 10(6) 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 x 10(4) 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.

Ruthenium and osmium complexes containing 2-(aminomethyl)pyridine (Ampy)-based ligands in catalysis

“…We found that the reaction of 36a with sodium isopropoxide in 2-propanol/C 6 D 6 afforded the alcohol-adduct alkoxide 60, which is in equilibrium with the hydride 38a/acetone mixture (Scheme 73) [52]. The hydride 38a was isolated from 36a and NaOiPr in 2-propanol/toluene by evaporation of the alcohol media and elimination of acetone under reduced pressure [32].…”

“…Moreover, 31 P-31 P NMR NOESY in solution revealed a rapid equilibrium between the alkoxide 37a and 38a/acetone mixture with an exchange rate of 2.9 ± 0.4 s −1 . Interestingly, the alkoxide 60 containing 2-propanol equilibrates with the hydride 38a with a significant higher rate (5.4 ± 0.2 s −1 ), showing that alcohol has a crucial role in enhancing the rate of exchange process [52]. Substitution in 36a of the NH 2 group with the NMe 2 function 36b produced a poorly active TH catalyst [32b].…”

“…Thus, the reaction of the isopropoxide 60 with bis(4-fluorophenyl)-or bis (3-nitrophenyl)methanone afforded the related alkoxide 64a [52] or 64b [38], respectively, via the hydride 38a; while reaction of 38a with benzophenone led to the alkoxide 64c [32b] (Scheme 74).…”

“…Further evidence of the involvement of alkoxide ruthenium species in the TH was given by catalytic and stoichiometric reduction of the prochiral ketone 2,2,2-trifluoro-1-(4-fluorophenyl)ethanone (117) involving the chiral CNN complex 115 prepared from RuCl 2 (PPh 3 ) 3 , the diphosphine (S,S)-Skewphos and the HCNN ligand (Scheme 76) [52]. When the alkoxide 116, obtained from 115 and NaOiPr in 2-propanol, was reacted with the ketone 117, a mixture of the diastereomer alkoxides 118a and 118b in a 5:1 molar ratio (67% ee) was obtained (74% yield) via Ru-hydride and elimination of acetone [52].…”

“…When the alkoxide 116, obtained from 115 and NaOiPr in 2-propanol, was reacted with the ketone 117, a mixture of the diastereomer alkoxides 118a and 118b in a 5:1 molar ratio (67% ee) was obtained (74% yield) via Ru-hydride and elimination of acetone [52]. Protonation of this mixture with acetic acid afforded (R)-and (S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethanol (R)-and (S)-119, respectively, with the complex R 1 R 2 conv (%) time ( R enatiomer prevailing (66% ee).…”