Enantioselective reactions of simple ketones, α,α- and β,β-dialkoxy ketones, and α-alkoxy ketones with trimethylsilyl cyanide catalyzed by the bimetallic systems of amino acid/BINAP/ruthenium(II) complexes and lithium phenoxide have been studied [BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl]. The Ru(PhGly)₂(BINAP)-lithium phenoxide system showed high enantioselectivity for the reaction of acetophenone derivatives to afford the cyanated products in up to 90% ee [PhGly=phenylglycinate]. For the cyanosilylation of dialkoxy ketones and α-alkoxy ketones, the Ru(t-Leu)₂(BINAP)-lithium phenoxide system exhibited the best catalyst performance to produce the cyanohydrin derivatives in up to 99% ee and 98% ee, respectively [t-Leu=tert-leucinate]. The excellent catalytic activity resulted in complete conversion in the reaction with a substrate-to-catalyst molar ratio (S/C) of 10,000 in the best cases.

The new catalyst system of RuBr₂[(S,S)-xyl-skewphos][(S,S)-dpen] and potassium tert-butoxide shows high reactivity and enantioselectivity in the hydrogenation of N-arylimines [Xyl-Skewphos=2,4-bis(di-3,5-xylylphosphino)pentane, DPEN=1,2-diphenylethylenediamine]. A range of imines derived from aromatic and heteroaromatic ketones as well as some ferrocenyl and vinylic imines are hydrogenated with a turnover number as high as 18,000 under 10–50 atm of hydrogen to afford the amine products in up to 99% enantiomeric excess. The reaction is applied to the synthesis of a chiral N-arylamine, which is the synthetic intermediate of a biologically active compound. The mode of enantioselection is interpreted by using transition-state models based on the X-ray structure of the Xyl-Skewphos/DPEN-RuBr₂ complex.

Development of highly active catalysts has been an important research area in synthetic chemistry, especially from a practical point of view. Herein, we focus on the homogeneous catalytic hydrogenation using well-defined molecular catalysts and discuss recent advances in the field with regard to the turnover number for these catalysts. DOI 10.1002/tcr.201100019

α-Substituted chiral ketones that have small steric and electronic differences around the reaction sites are difficult substrates to reduce with high diastereoselectivity. Metal hydride reduction of 2-(4-benzoylmorpholinyl) phenyl ketone and 3-(1-tert-butoxycarbonylpiperidinyl) phenyl ketone using sodium borohydride, zinc borohydride, and potassium tri-sec-butylborohydride as reducing agents affords the syn- and anti-alcohols in a lower than 80:20 ratio. Hydrogenation of these ketones with a catalyst system of RuCl₂(BIPHEP)(DMEN) and potassium tert-butoxide in 2-propanol results in the syn-alcohols with ≥ 99:1 selectivity [BIPHEP=2,2′-bis(diphenylphosphino)biphenyl, DMEN=N,N-dimethylethylenediamine]. The marked difference in the diastereoselectivity suggests that the stereoselection in this hydrogenation is primarily regulated by the structure of the catalyst’s reaction field (“catalyst-controlled diastereoselection”) but not the internal stereocontrol of the substrates. This chemistry is applied to the asymmetric hydrogenation through dynamic kinetic resolution with a RuCl₂[(S)-BINAP][(R)-DMAPEN]/potassium tert-butoxide catalyst [BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, DMAPEN=2-dimethylamino-1-phenylethylamine]. A series of aryl heterocycloalkyl ketones has been converted to the alcohols in excellent diastereo- and enantioselectivities. The modes of catalyst-controlled diastereoselection and enantioselection are interpreted by using transition-state molecular models. (S,S)-Reboxetine, a selective norepinephrine uptake inhibitor, was synthesized from one of product alcohols.

The asymmetric reaction of α-keto esters and (CH₃)₃SiCN, catalyzed by a combined system of [Ru{(S)-phgly}₂{(S)-binap}] and C₆H₅OLi with a substrate-to-catalyst molar ratio (S/C) of 1000 at –60 °C, affords silylated cyanohydrins in up to 99 % ee. Cyanosilylation smoothly proceeds with an S/C of 10,000 at –50 °C. The use of Xyl-Binap instead of Binap as a ligand provides better enantioselectivity in some cases. A series of aromatic, hetero-aromatic, aliphatic, and α,β-unsaturated keto esters are converted into the desired products.

Palladium nanoparticles are prepared from palladium(II) acetate and 2 equivalents of potassium tert-butoxide in the presence of 4-octyne. The palladium nanoparticles-tetrabutylammonium borohydride system shows excellent catalytic activity and selectivity in the semihydrogenation of alkynes to the [(Z)-]alkenes. The hydrogenation of 4-octyne is conducted with the catalyst system at a substrate-to-palladium molar ratio of 10,000–200,000 under 8 atm of hydrogen to give (Z)-4-octene in>99% yield. Isomerization and over-reduction of the Z-alkene are very slow even after consumption of the alkyne.

Enantiomer-selective carbamoylation of racemic α-hydroxy γ-lactones with half equivalents of isocyanates in the presence of chiral Cu^II catalysts was studied. Among a series of catalyst bearing chiral bis(oxazoline) (box) and pyridine(bisoxazoline) ligands, [Cu(tBu-box)]X₂ [X=OSO₂CF₃ (3 a), SbF₆ (3 b)] showed the highest enantioselectivity in the reaction of pantolactone (1 a). Use of n-C₃H₇NCO, a small alkyl isocyanate, in CH₂Cl₂ solution was important to achieve a high level of enantiomer selection. The tBu-box-Cu^II catalyst efficiently differentiated two enantiomers of β-substituted α-hydroxy γ-lactones under the optimized reaction conditions, resulting in a stereoselectivity factor (s=k_fast/k_slow) of up to 209. Furthermore, this catalyst is highly active, so that the carbamoylation can be conducted with a substrate-to-catalyst molar ratio of 2000–3000. A catalytic cycle of this reaction is also proposed.