Asymmetric hydrogenation of aromatic ketones using new chiral-bridged diphosphine/diamine-Ru(Ⅱ) complexes

<正>A series of chiral secondary alcohols were easily prepared by means of asymmetric hydrogenation of prochiral aromatic ketones using a new((R_(ax))-BuP)/(R,R)-DPEN-Ru(Ⅱ) complex catalyst system.The hydrogenation of 2-methylacetophenone in n-butanol (t-BuOK/Ru =45.6/1,S/C = 500,20 atm.of H_2,20℃,48 h) afforded(S)-1-(2'-methylphenyl)ethanol in 92%ee and99% conversion.     

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.     

A remarkably effective catalyst for the asymmetric transfer hydrogenation of aromatic ketones in water and air

A Rh(III) complex generated in situ from [Cp*RhCl2]2 and (1R,2R)-N-(p-toluenesulfonyl)-1,2-cyclohexanediamine (TsCYDN) serves as a remarkably effective, robust catalyst for the asymmetric transfer hydrogenation of aromatic ketones by HCOONa in water in air, affording alcohols in up to 99% ee.     

General asymmetric hydrogenation of hetero-aromatic ketones

trans-RuCl(2)[(R)-xylbinap][(R)-daipen] or the S,S complex acts as an efficient catalyst for asymmetric hydrogenation of hetero-aromatic ketones. The hydrogenation proceeds with a substrate-to-catalyst molar ratio of 1000-40000 to give chiral alcohols in high ee and high yield. The enantioselectivity appears to be little affected by the properties of the hetero-aromatic ring. This method allows for asymmetric synthesis of duloxetine, an inhibitor of serotonin and norepinephrine uptake carriers.     

Asymmetric transfer hydrogenation of benzaldehydes

A combined system of RuCl[(R, R)-YCH(C(6)H(5))CH(C(6)H(5))NH(2)](eta(6)-arene) (Y = NSO(2)C(6)H(4)-4-CH(3) or O) and t-C(4)H(9)OK catalyzes the asymmetric transfer hydrogenation of various benzaldehyde-1-d derivatives with 2-propanol to yield (R)-benzyl-1-d alcohols in 95-99% ee and with >99% isotopic purity. Reaction of benzaldehydes with a DCO(2)D-triethylamine mixture and the R,R catalyst affords the S deuterated alcohols in 97-99% ee.     

Structure-enantioselectivity effects in 3,4-dihydropyrimido[2,1-b]benzothiazole-based isothioureas as enantioselective acylation catalysts

The catalytic activity and enantioselectivity in the kinetic resolution of (±)-1-naphthylethanol with a range of structurally related 3,4-dihydropyrimido[2,1-b]benzothiazole-based catalysts is examined. Of the isothiourea catalysts screened, (2S,3R)-2-phenyl-3-isopropyl substitution proved optimal, giving good levels of selectivity in the kinetic resolution of a number of secondary alcohols (S values up to >100 at ~50% conversion). Low catalyst loadings (0.10-0.25 mol%) of the optimal isothiourea can be used to generate enantiopure alcohols (>99% ee) in good yields.     

Application of chiral mixed phosphorus/sulfur ligands to enantioselective rhodium-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation processes

Chiral mixed phosphorus/sulfur ligands 1-3 have been shown to be effective in enantioselective Rh-catalyzed dehydroamino acid hydrogenation and ketone hydrosilylation reactions (eqs 1, 2). After assaying the influence of the substituents at sulfur, the substituents on the ligand backbone, the relative stereochemistry within the ligand backbone, and the substituents at phosphorus, ligands 2c (R = 3,5-dimethylphenyl) and 3 were found to be optimal in the Rh-catalyzed hydrogenation of a variety of alpha-acylaminoacrylates in high enantioselectivity (89-97% ee). A similar optimization of the catalyst for the Rh-catalyzed hydrosilylation of ketones showed that ligand 3 afforded the highest enantioselectivities for a wide variety of aryl alkyl and dialkyl ketones (up to 99% ee). A model for asymmetric induction in the hydrogenation reaction is discussed in the context of existing models, based on the absolute stereochemistry of the products and the X-ray crystal structures of catalyst precursors and intermediates.     

Asymmetric transfer hydrogenation of aryl ketones catalyzed by salt-free two samarium centers supported by a chiral multidentate alkoxy ligand

[reaction: see text] We synthesized a chiral multidentate ligand, (R,R,R,R)-N,N,N',N'-tetra(2-hydroxy-2-phenylethyl)-1,3-xylylene diamine [(R)-2], which can support two metals at adjacent positions. Asymmetric transfer hydrogenation of acetophenone and its derivatives was conducted by using salt-free bimetallic lanthanoid complexes of (R)-2, and the combination of two samarium atoms and (R)-2 was found to be the best catalyst system for asymmetric transfer hydrogenation of aryl ketones in high enantioselectivity (up to >99% ee).     

Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones

Novel chiral multidentate P₃N₄-type ligand has been synthesized and characterized by NMR and HRMS. Using i-PrOH as solvent and hydrogen source, asymmetric transfer hydrogenation of various ketones was investigated. The catalyst generated in situ from chiral multidentate aminophosphine ligand (R,R,R,R)-3 and IrCl(CO)(PPh₃)₂ exhibited highly catalytic activity and excellent enantioselectivity under mild conditions, achieving the corresponding chiral alcohols with up to 99% yield and 99% ee.     

Applications of ruthenium hydride borohydride complexes containing phosphinite and diamine ligands to asymmetric catalytic reactions

[reaction: see text] A series of novel trans-ruthenium hydride borohydride complexes with chiral phosphinite and diamine ligands were synthesized. They can be used in the asymmetric transfer hydrogenation of aryl ketones, including base-sensitive ones, to give chiral alcohols in moderate to good enantioselectivities (up to 94% ee). They are also efficient catalysts for the Michael addition of malonates to enones with enantioselectivities of up to 90%. This kind of catalyst allows a one-pot tandem Michael addition/H(2) hydrogenation protocol to build structures with multiple chiral centers.     

Synthesis of enantiopure 3,6,7,8-tetrahydrochromeno[7,8-d]imidazoles via asymmetric ketone hydrogenation in the presence of RuCl2[Xyl-P-Phos][DAIPEN]

The asymmetric hydrogenation of complex heterocyclic ketones 1 in the presence of the novel catalyst RuCl₂[(S)-Xyl-P-Phos][(S)-DAIPEN] and a base afforded the corresponding alcohols 2 in good enantiomeric purity. The outcome of the reaction depended on the substitution pattern of the ketone and the stoichiometry of the base. After optimization of the reaction conditions, the pure alcohols 2a and 2b were isolated in good yield (>70%) and enantiomeric purity (>93% ee) and used as key intermediates for the synthesis of the pharmaceutically active 3,6,7,8-tetrahydrochromeno[7,8-d]imidazoles 3a and 3b.     

Asymmetric hydrogenation of enol phosphinates catalyzed by a chiral ferrocenylphosphine-rhodium complex. Asymmetric synthesis of optically active secondary alkyl alcohols

Catalytic asymmetric synthesis of secondary alkyl alcohols (up to 78% ee) was accomplished by asymmetric hydrogenation of enol diphenylphosphinates, derived from prochiral ketones such as acetophenone, 3-methyl-2-butanone, and 2-octanone, in the presence of a cationic rhodium complex of (R)-1-[(C)-1′,2-bis(diphenylphosphino)ferrocenyl]ethanol (BPPFOH).     

Enantioselective synthesis of (2-pyridyl)alanines via catalytic hydrogenation and application to the synthesis of L-azatyrosine

[reaction: see text] A novel method for the synthesis of (2-pyridyl)alanines 2a-b was developed by converting (2-pyridyl)dehydroamino acid derivatives 1a-b to the corresponding N-oxides 3a-b followed by asymmetric hydrogenation using (R,R)-[Rh(Et-DUPHOS)(COD)]BF(4) [(R,R)-6] catalyst and subsequent N-oxide reduction in 80-83% ee. This methodology was applied to the total synthesis of L-azatyrosine [(+)-12], an antitumor antibiotic, starting from (5-benzyloxy)-2-pyridylmethanol (7), in >96% enantiomeric purity.     

手性修饰的介孔碳材料MPC-61负载铂催化剂上α-酮酸酯的不对称氢化反应

采用氯铂酸乙醇溶液和氯铂酸水溶液为前体,通过浸渍法制备了介孔碳材料MPC-61负载Pt质量分数分别为4%和10%的Pt/MPC-61催化剂,并利用XRD,TEM,N2吸附-脱附和CO化学吸附等手段对催化剂进行了表征.考察了经过手性分子辛可尼定修饰后的Pt/MPC-61催化剂在丙酮酸乙酯不对称氢化反应中的催化性能.以氯铂...     

New functional chiral P-based ligands and application in ruthenium-catalyzed enantioselective transfer hydrogenation of ketones

Metal-catalyzed asymmetric transfer hydrogenation is a powerful and practical method for the reduction of ketones to produce the corresponding secondary alcohols, which are valuable building blocks in the pharmaceutical, perfume, and agrochemical industries. Hence, a series of novel chiral β-amino alcohols were synthesized by chiral amines with regioselective ring opening of (S)-propylene oxide or reaction with (S)-(+)-2-hydroxypropyl p-toluenesulfonate by a straightforward method. The chiral ruthenium catalytic systems generated from [Ru(arene)(μ-Cl)Cl]₂ complexes and chiral phosphinite ligands based on amino alcohol derivatives were employed in asymmetric transfer hydrogenation of ketones to give the corresponding optically active alcohols; (2S)-1-{[(2S)-2-[(diphenylphosphanyl)oxy]propyl][(1R)-1-phenylethyl]amino}propan-2-yldiphenylphosphinitobis[dichol-oro(η⁶-benzene)ruthenium(II)] acts an excellent catalyst in the reduction of α-naphthyl methyl ketone, giving the corresponding alcohol with up to 99% ee. The substituents on the backbone of the ligands were found to have a remarkable effect on both the conversion and enantioselectivity of the catalysts. Furthermore, this transfer hydrogenation is characterized by low reversibility under these conditions.     

Ru-Catalyzed asymmetric hydrogenation of alpha-ketoesters with CeCl3.7H2O as additive

[reaction: see text] An efficient asymmetric hydrogenation of alpha-ketoesters is reported with use of a catalyst prepared from [Ru((S)-3)(benzene)Cl]Cl and CeCl(3).7H(2)O. Alpha-hydroxy esters are obtained in up to 96% ee. The addition of CeCl(3).7H(2)O not only improves the enantioselectivity, but also enhances the stability of the catalyst. As a result, the hydrogenation of methyl benzoylformate affords the product with 92% ee with a substrate/catalyst ratio of 10 000. Hydrolysis of 2 provides the final compound with 83% yield at 99% ee after a single recrystallization from 1,2-dichloroethylene.     

Synthesis of a novel chiral binaphthyl phospholane and its application in the highly enantioselective hydrogenation of enamides

[formula: see text] A new chiral phosphine, (R,R)-1,2-bis[(R)-4,5-dihydro-3H-dinaphtho[2,1- c:1',2'-e]phosphepino]benzene [abbreviated as (R,R)-binaphane] was prepared on the basis of a practical route from a readily accessible enantiomerically pure binaphthanol. This ligand possesses both binaphthyl chirality and phospholane functionality. Excellent enantioselectivities (95-99.6% ee) have been observed in hydrogenation of an isomeric mixture of (E)- and (Z)-beta-substituted-alpha-arylenamides by using a Rh-binaphane catalyst. These enantioselectivities are the highest reported to date for this transformation.     

Asymmetric transfer hydrogenation of ketones in 2-propanol catalyzed by arsinooxazoline-ruthenium(II) complex

Chiral arsinooxazoline Ru(II) complex has been found to be an efficient catalyst for asymmetric transfer hydrogenation of aromatic ketones in 2-propanol. Secondary alcohols with up to 94% enantiomeric excess were obtained at a substrate/catalyst mole ratio of 1000:1. Asymmetric kinetic resolution has also been obtained with 1-arylalkanols at room temperature with 99% ee.     

2-Azanorbornyl alcohols: very efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic ketones

2-Azanorbornyl-derived amino alcohols were prepared and evaluated as ligands in the Ru(II)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. To improve selectivity and rate, the structure of the ligand was optimized. Acetophenone was reduced using 0.5 mol % catalyst in 40 min in 94% ee. This system was also able to reduce a wide range of aromatic ketones to the corresponding alcohols, while maintaining high enantioselectivities and yields. The effects of catalyst loading and the presence of cosolvents in the reaction vessel were examined, and a linearity study was also done.     

Rhodium-catalyzed asymmetric hydrogenation of functionalized olefins using monodentate spiro phosphoramidite ligands

Novel chiral monodentate phosphorus ligands, SIPHOS, were conveniently synthesized from 1,1'-spirobiindane-7,7'-diol. The Rh complexes of SIPHOS can catalyze the hydrogenation of alpha-dehydroamino esters in mild conditions, providing alpha-amino acid derivatives in up to 99% ee. Enamides and beta-dehydroamino esters can also be hydrogenated in good to excellent enantioselectivities (up to 99% and 94% ee, respectively). The SIPHOS ligand with smaller alkyl groups on the N-atom afforded higher enantioselectivity. The X-ray analysis of single crystal showed that the structure of Rh/SIPHOS catalyst is [Rh(COD)((S)-SIPHOS-Me)(2)](+), which clarified the configuration of the catalyst with the monodentate chiral phosphorus ligand in Rh-catalyzed asymmetric hydrogenation. A positive nonlinear effect in the relationship of the optical purities of ligand and product was observed in the hydrogenation of dehydroamino acid derivatives. The kinetic study of hydrogenation showed that the reaction is zero order in the concentration of substrate and first order in the concentration of Rh catalyst and the hydrogenation pressure. The rate of hydrogenation decreased when the Rh/L ratio changed from 1:1 to 1:4.