General asymmetric hydrogenation of alpha-branched aromatic ketones catalyzed by TolBINAP/DMAPEN-ruthenium(II) complex

[reaction: see text] A catalyst system consisting of RuCl2[(S)-tolbinap][(R)-dmapen] and t-C4H9OK in 2-propanol effects asymmetric hydrogenation of arylglyoxal dialkylacetals to give the alpha-hydroxy acetals in up to 98% ee. Hydrogenation of racemic alpha-amidopropiophenones under dynamic kinetic resolution predominantly gives the syn alcohols in up to 99% ee and >98% de, while the reaction of racemic bezoin methyl ether gives the anti alcohols in excellent stereoselectivity.     

Mechanism of the hydrogenation of ketones catalyzed by trans-dihydrido(diamine)ruthenium II complexes

The complexes trans-RuH(Cl)(tmen)(R-binap) (1) and (OC-6-43)-RuH(Cl)(tmen)(PPh(3))(2) (2) are prepared by the reaction of the diamine NH(2)CMe(2)CMe(2)NH(2) (tmen) with RuH(Cl)(PPh(3))(R-binap) and RuH(Cl)(PPh(3))(3), respectively. Reaction of KHB(sec)Bu(3) with 1 yields trans-Ru(H)(2)(R-binap)(tmen) (5) while reaction of KHB(sec)Bu(3) or KO(t)Bu with 2 under Ar yields the new hydridoamido complex RuH(PPh(3))(2)(NH(2)CMe(2)CMe(2)NH) (4). Complex 4 has a distorted trigonal bipyramidal geometry with the amido nitrogen in the equatorial plane. Loss of H(2) from 5 results in the related complex RuH(R-binap)(NH(2)CMe(2)CMe(2)NH) (3). Reaction of H(2) with 4 yields the trans-dihydride (OC-6-22)-Ru(H)(2)(PPh(3))(2)(tmen)(6). Calculations support the assignment of the structures. The hydrogenation of acetophenone is catalyzed by 5 or 4 in benzene or 2-propanol without the need for added base. For 5 in benzene at 293 K over the ranges of concentrations [5] = 10(-)(4) to 10(-)(3) M, [ketone] = 0.1 to 0.5 M, and of pressures of H(2) = 8 to 23 atm, the rate law is rate = k[5][H(2)] with k = 3.3 M(-1) s(1), DeltaH++ = 8.5 +/- 0.5 kcal mol(-1), DeltaS++ = -28 +/- 2 cal mol(-1) K(-1). For 4 in benzene at 293 K over the ranges of concentrations [4] = 10(-4) to 10(-3) M, [ketone] 0.1 to 0.7 M, and of pressures of H(2) = 1 to 6 atm, the preliminary rate law is rate = k[4][H(2)] with k = 1.1 x 10(2) M(-1) s(-1), DeltaH++ = 7.6 +/- 0.3 kcal mol(-1), DeltaS++ = -23 +/- 1 cal mol(-1) K(-1). Both theory and experiment suggest that the intramolecular heterolytic splitting of dihydrogen across the polar Ru=N bond of the amido complexes 3 and 4 is the turn-over limiting step. A transition state structure and reaction energy profile is calculated. The transfer of H(delta+)/H(delta-) to the ketone from the RuH and NH groups of 5 in a Noyori metal-ligand bifunctional mechanism is a fast process and it sets the chirality as (R)-1-phenylethanol (62-68% ee) in the hydrogenation of acetophenone. The rate of hydrogenation of acetophenone catalyzed by 5 is slower and the ee of the product is low (14% S) when 2-propanol is used as the solvent, but both the rate and ee (up to 55% R) increase when excess KO(t)Bu is added. The formation of ruthenium alkoxide complexes in 2-propanol might explain these observations. Alkoxide complexes [RuP(2)]H(OR)(tmen), [RuP(2)] = Ru(R-binap) or Ru(PPh(3))(2), R= (i) Pr, CHPhMe, (t)Bu, are observed by reacting the alcohols (i)PrOH, phenylethanol, and (t)BuOH with the dihydrides 5 and 6, respectively, under Ar. In the absence of H(2), the amido complexes 3 and 4 react with acetophenone to give the ketone adducts [RuP(2)]H(O=CPhMe)(NH(2)CMe(2)CMe(2)NH) in equilibrium with the enolate complexes trans- [RuP(2)](H)(OCPh=CH(2))(tmen) and eventually the decomposition products [RuP(2)]H(eta(5)-CH(2)CPhCHCPhO), with the binap complex characterized crystallographically. In general, proton transfer from the weakly acidic molecules dihydrogen, alcohol, or acetophenone to the amido nitrogen of complexes 3 and 4 is favored in two ways when the molecule coordinates to ruthenium: (1) an increase in acidity of the molecule by the Lewis acidic metal and (2) an increase in the basicity of the amido nitrogen caused by its pyramidalization. The formato complexes trans-[RuP(2)]H(OCHO)(tmen) were prepared by reacting the respective complex 4 or 5 with formic acid. The crystal structure of RuH(OCHO)(PPh(3))(2)(tmen) displays similar features to the calculated transition state for H(delta+)/H(delta-) transfer to the ketone in the catalytic cycle.     

Mechanism of asymmetric hydrogenation of ketones catalyzed by BINAP/1,2-diamine-rutheniumII complexes

Asymmetric hydrogenation of acetophenone with trans-RuH(eta(1)-BH(4))[(S)-tolbinap][(S,S)-dpen] (TolBINAP = 2,2'-bis(di-4-tolylphosphino)-1,1'-binaphthyl; DPEN = 1,2-diphenylethylenediamine) in 2-propanol gives (R)-phenylethanol in 82% ee. The reaction proceeds smoothly even at an atmospheric pressure of H(2) at room temperature and is further accelerated by addition of an alkaline base or a strong organic base. Most importantly, the hydrogenation rate is initially increased to a great extent with an increase in base molarity but subsequently decreases. Without a base, the rate is independent of H(2) pressure in the range of 1-16 atm, while in the presence of a base, the reaction is accelerated with increasing H(2) pressure. The extent of enantioselection is unaffected by hydrogen pressure, the presence or absence of base, the kind of base and coexisting metallic or organic cations, the nature of the solvent, or the substrate concentrations. The reaction with H(2)/(CH(3))(2)CHOH proceeds 50 times faster than that with D(2)/(CD(3))(2)CDOD in the absence of base, but the rate differs only by a factor of 2 in the presence of KO-t-C(4)H(9). These findings indicate that dual mechanisms are in operation, both of which are dependent on reaction conditions and involve heterolytic cleavage of H(2) to form a common reactive intermediate. The key [RuH(diphosphine)(diamine)](+) and its solvate complex have been detected by ESI-TOFMS and NMR spectroscopy. The hydrogenation of ketones is proposed to occur via a nonclassical metal-ligand bifunctional mechanism involving a chiral RuH(2)(diphosphine)(diamine), where a hydride on Ru and a proton of the NH(2) ligand are simultaneously transferred to the C=O function via a six-membered pericyclic transition state. The NH(2) unit in the diamine ligand plays a pivotal role in the catalysis. The reaction occurs in the outer coordination sphere of the 18e RuH(2) complex without C=O/metal interaction. The enantiofaces of prochiral aromatic ketones are kinetically differentiated on the molecular surface of the coordinatively saturated chiral RuH(2) intermediate rather than in a coordinatively unsaturated Ru template.     

Highly enantioselective hydrogenation of (E)-beta-(acylamino)acrylates catalyzed by Rh(i)-complexes of electron-rich P-chirogenic diphosphines

Excellent enantioselectivities up to 99.7% were achieved in the hydrogenation of (E)-beta-(acylamino)acrylates by the use of Rh(I)-complexes of electron-rich diphosphines, t-Bu-BisP and t-Bu-MiniPHOS. Low-temperature NMR experiments testify that monohydrides with beta-carbon atom of the substrate bound to rhodium are involved in the catalytic cycle.     

水溶性铑-膦配合物催化丙烯酸酯类的氢甲酰化反应研究

随温度升高,丙烯酸甲酯和丙烯酸丁酯的氢甲酰化反应产物中α/β醛的比例无明显变化,但加氢产物增多。而甲基丙烯酸甲酯的加氢产物非常少。三种丙烯酸酯氢甲酰化反应的TOF值排序:丙烯酸甲酯>丙烯酸丁酯>甲基丙烯酸甲酯与它们在水中的溶解度排序相同,这说明在两相催化体系中,含功能基团丙烯酸酯类底物的氢甲酰化反应受传质的影响很大,它们溶入水中的量是决定其反应速度快慢的关键因素。     

Manganese catalyzed asymmetric transfer hydrogenation of ketones

The asymmetric transfer hydrogenation (ATH) of a wide range of ketones catalyzed by manganese complex as well as chiral P_xN_y-type ligand under mild conditions was investigated. Using 2-propanol as hydrogen source, various ketones could be enantioselectively hydrogenated by combining cheap, readily available [MnBr(CO)₅] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP₂N₄ (L5) with 2 mol% of catalyst loading, affording highly valuable chiral alcohols with up to 95% ee.     

Highly efficient asymmetric transfer hydrogenation of ketones catalyzed by chiral ‘roofed’ cis-diamine-Ru(II) complex

A new type of chiral Ru(II) complex, prepared from a conformationally rigid, sterically bulky ‘roofed’ cis-diamine and [RuCl₂(benzene)]₂, functions as an efficient catalyst for the asymmetric transfer hydrogenation of a wide variety of aryl ketones, including sterically bulky ketones, when the reaction is conducted in the presence of 5HCO₂H·2NEt₃.     

Direct asymmetric aldol reactions catalyzed by nanocrystalline copper(II) oxide

The direct asymmetric aldol reactions of aromatic and heteroaromatic aldehydes with acetone to afford chiral β-hydroxy carbonyl compounds in good yields and good to moderate enantioselectivities are realized using nanocrystalline copper(II) oxide in the presence of (1S,2S)-(−)-1,2-diphenylethylenediamine at −30 °C. The catalyst can be reused for four cycles with consistent activity and enantioselectivity.     

The asymmetric hydrogenation of α-keto esters catalyzed by rhodium(I) complexes with chiral diphosphine ligands. On the catalytic cycles and the mechanism of asymmetric induction

Asymmetric hydrogenations of n-propyl pyruvate and ketopantoyl lactone catalyzed by rhodium complexes with (—) DIOP and BPPM were carried out under a variety of conditions. It was found that i) the Schrock-Osborn mechanism was not operative in these reactions at all since no acceleration of the reaction rate by the addition of water (1%) was observed, ii) there was a clear difference between cationic and neutral (in situ) rhodium catalysts in their enantioselectivity, and iii) there was a remarkable solvent effect on the extent and direction of asymmetric induction. Possible mechanisms are discussed on the basis of these results.     

Biomimetic asymmetric hydrogenation: in situ regenerable Hantzsch esters for asymmetric hydrogenation of benzoxazinones

A catalytic amount of Hantzsch ester that could be regenerated in situ by Ru complexes under hydrogen gas has been employed in the biomimetic asymmetric hydrogenation of benzoxazinones with up to 99% ee in the presence of chiral phosphoric acid. The use of hydrogen gas as a reductant for the regeneration of Hantzsch esters makes this hydrogenation an ideal atom economic process.     

Metal-free asymmetric hydrogenation and hydrosilylation catalyzed by frustrated Lewis pairs

The activation of H₂ for the catalytic hydrogenation of unsaturated compounds is one of the most useful reactions in both academia and chemical industry, which has long been predominated by the transition-metal catalysis. However, metal-free hydrogen activation represents a formidable challenge, and has been less developed. The recent emerging chemistry of frustrated Lewis pairs (FLPs) with a combination of sterically encumbered Lewis acids and Lewis bases provides a promising approach for metal-free hydrogenation due to their amazing abilities for the challenging H₂ activation. In the past several years, the hydrogenation of a wide range of unsaturated compounds using FLP catalysts has been successfully developed. Despite these advances, the corresponding asymmetric hydrogenation is just in its start-up step. Similar to the mode of HH bond activation, SiH bond can also be activated by FLPs for the hydrosilylation of ketones and imines. But its asymmetric version is also not well-solved. This Letter will outline the recent important progress of metal-free catalytic asymmetric hydrogenation and hydrosilylation using FLP catalysts.     

Ru-catalyzed highly enantioselective hydrogenation of beta-alkyl-substituted beta-(acylamino)acrylates

Highly enantioselective hydrogenation of beta-alkyl-substituted (E)-beta-(acylamino)-acrylates catalyzed by Ru((R)-Xyl-P-Phos)(C(6)H(6))Cl(2) complex (cat. 1c) was achieved in up to 99.7% ee. Moderate to good enantioselectivities in the hydrogenation of corresponding (Z)-isomers in the presence of [Rh((R)-Xyl-P-Phos)(COD)]BF(4) (cat. 2c) were also obtained. The results demonstrated that the electronic and steric properties of the dipyridylphosphine ligands as well as the different transition metal ions have significant influences on the catalytic properties in the hydrogenation of beta-(acylamino)acrylates.     

Direct asymmetric aldol condensation catalyzed by aziridine semicarbazide zinc(II) complexes

Previously obtained semicarbazides derived from N-triphenylmethyl-aziridine-2-carbohydrazide were explored as ligands in Zn(II) catalyzed diastereo- and enantioselective direct aldol reactions. Complexes of aziridine-semicarbazides with Zn(II) were efficient catalysts in reactions of acetone and hydroxyacetone with NO₂-substituted aromatic aldehydes in the presence of water.     

Rh(I)/DpenPhos catalyzed asymmetric hydrogenation of enol esters and potassium (E)-3-cyano-5-methylhex-3-enoate

Rh(I) complexes of a class of modular chiral monodentate phosphoramidites were highly efficient for the asymmetric hydrogenation of enol esters bearing α-aryl or α-alkyl groups, to afford the corresponding hydrogenation products in high enantioselectivities (87–95% ee) and reactivities (turnover number up to 10,000). These ligands were also shown to be effective in Rh(I)-catalyzed asymmetric hydrogenation of the potassium salt of (E)-3-cyano-5-methylhex-3-enoate, to give the corresponding product (a precursor to CI-1008) with up to 95% ee and complete conversion of substrate.     

Enantioselective hydrogenation of tetrasubstituted olefins of cyclic beta-(acylamino)acrylates

Hydrogenation of a series of cyclic beta-(acylamino)acrylates with tetrasubstituted olefins has been accomplished successfully with the use of Ru catalysts with chiral biaryl ligands such as C3-TunaPhos, and up to over 99% ee's have been achieved. This methodology provides an efficient catalytic method for the synthesis of both cis and trans chiral cyclic beta-amino acid derivatives.