Homogeneous asymmetric catalysis by means of chiral metal complexes of 2,3-bis(dimenthylphosphino)maleic anhydride and of 2,3-bis(dimenthylphosphino)maleimide derivatives

2,3-Bis(dimenthylphosphino)maleic anhydride and also 2,3-bis(dimenthylphosphino)maleimide derivatives have been prepared from 2,3-dichloromaleic anhydride, 2,3-dichloro-N-phenylmaleimide and 2,3-dichloro-N-methylmaleimide, respectively, and dimenthyl(trimethylsilyl)phosphine. These compounds have been used as ligands for Rh complexes in the asymmetric hydrogenation and hydrosilylation. Ni and Pd complexes of these ligands were tested in the Grignard cross-coupling reaction.

The hydrogenation of -acetamido cinnamic acid gave 70% enantiomeric excess (ee) and hydrogenation of acetophenone up to 47% ee. Hydrosilylation of acetophenone led to 42% ee.

Attempts to asymmetric cross-coupling reactions resulted in very low enantiomeric excess.     

Synthesis of new monodentate spiro phosphoramidite ligand and its application in Rh-catalyzed asymmetric hydrogenation reactions

[reaction: see text] A new spirocyclic diol, 9,9'-spirobixanthene-1,1'-diol, was synthesized in two steps from readily available starting material m-phenoxyanisole. Resolution of the racemic diol was achieved by cocrystallization with N-benzylcinchonidinium chloride and N-benzylquininium chloride in acetonitrile. The corresponding spiro monodentate phosphoramidite ligand has been prepared for Rh-catalyzed asymmetric hydrogenation of alpha-dehydroamino acid derivatives and itaconic acid with excellent enantioselectivities (up to >99% ee).     

Asymmetric Rh-catalyzed hydrogenation using a furanoside phosphite-phosphoroamidite and diphosphoroamidite ligand library

A furanoside phosphite-phosphoroamidite and diphosphoroamidite ligand library L1-L5a-f was tested in the asymmetric Rh-catalyzed hydrogenation of α,β-unsaturated carboxylic acid derivatives and enamides. Enantioselectivity depended strongly on the ligand parameters. High enantioselectivities were obtained in the reduction of dimethyl itaconate (up to >99% ee), α-dehydroamino acid esters (up to 99% ee) and several enamides (up to 92% ee). Kinetic and NMR studies on the intermediates of the catalytic cycle of the reaction indicate that the [Rh(P(1)-P(2))(substrate)](+) species is the resting state of the reaction and that the rate dependence is first order in rhodium and hydrogen pressure and zeroth order in the substrate.     

Highly efficient rhodium/monodentate phosphoramidite catalyst and its application in the enantioselective hydrogenation of enamides and alpha-dehydroamino acid derivatives

An easily prepared and highly efficient monodentate phosphoramidite ligand derived from BINOL, (S)-2,2'-O,O-(1,1'-binaphthyl)-dioxo-N,N-diethylphospholidine, was examined in the hydrogenation of both enamides and alpha-dehydroamino acid derivatives. The catalyst provided remarkably high enantioselectivities (up to 99.6% ee for enamides and >99.9% ee for alpha-dehydroamino acid derivatives).     

Enantioselective Rh-catalyzed hydrogenation of N-formyl dehydroamino esters with monodentate phosphoramidite ligands

Enantioselectivities up to >99% ee were achieved in the rhodium-catalyzed asymmetric hydrogenation of N-formyl dehydroamino esters using monodentate phosphoramidites as chiral ligands. The substrates were synthesized by condensation of methyl isocyanoacetate with a range of aldehydes and with cyclohexanone. A highly convenient multigram scale one step synthesis of methyl 2-(formamido)acrylate was developed. This compound was used in the synthesis of methyl 2-(formamido)cinnamate via a solvent free Heck reaction. Moreover, full conversion and >99% ee were obtained in 1 h in the hydrogenation of methyl 2-(formamido)acrylate with 0.2 mol % catalyst and 2 bar hydrogen pressure. The versatility of the formyl protection was established by its removal under mild conditions.     

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.     

Regiodivergent Synthesis of 11H-Indolo[3,2-c]quinolines and Neocryptolepine from a Common Starting Material

A large number of diversely functionalized analogs of the bioactive natural products neocryptolepine and isocryptolepine have been prepared from a series of 3-bromoquinoline derivatives. The neocryptolepines were obtained by a Pd⁰-catalyzed C−C bond coupling followed by C−N bond formation in yields up to 80 %, whereas the indoloquinolines were prepared by a Suzuki-Miyaura cross-coupling followed by azidation-photochemical cyclization in yields ranging from traces to 95 % yield.     

Resolution of racemic 2-aminocyclohexanol derivatives and their application as ligands in asymmetric catalysis

A preparatively easy and efficient protocol for the resolution of racemic 2-aminocyclohexanol derivatives is described, delivering both enantiomers with >99% enantiomeric excess (ee) by sequential use of (R)- and (S)-mandelic acid. A simple aqueous workup procedure permits the isolation of the amino alcohols in analytically pure form and the almost quantitative recovery of mandelic acid. Debenzylation of enantiopure trans-2-(N-benzyl)amino-1-cyclohexanol by hydrogenation and subsequent derivatization give access to a broad variety of diversely substituted derivatives. Furthermore, the corresponding cis isomers are readily available. Applications of these optically active aminocyclohexanols in catalyzed asymmetric phenyl transfer reactions to benzaldehydes and transfer hydrogenations of aryl ketones lead to products with up to 96% ee.     

Microwave assisted asymmetric Suzuki-Miyaura and Negishi cross-coupling reactions: synthesis of chiral binaphthalenes

Microwave assisted asymmetric Suzuki-Miyaura and Negishi enantioselective cross-coupling reactions are reported for the first time, and have been applied to the rapid synthesis of chiral sterically hindered binaphthalene derivatives in reasonable to excellent yields (65–96%) and fair to good enantioselectivities (43–70% ee).     

Highly efficient desymmetrisation of a tricarbonylchromium 1,4-dibromonaphthalene complex by asymmetric Suzuki-Miyaura coupling

Access to planar chiral complexes has been sought by catalytic desymmetrisation of a prochiral complex via asymmetric Suzuki-Miyaura cross-coupling. High selectivities of up to 98% ee were achieved using a bulky chiral palladium catalyst.     

Efficient enantioselective hetero-Diels-Alder reaction of Brassard's diene with aliphatic aldehydes: a one-step synthesis of (R)-(+)-kavain and (S)-(+)-dihydrokavain

An efficient catalytic asymmetric hetero-Diels-Alder reaction of Brassard's diene with aliphatic aldehydes was reported. The catalyst, which was generated from (R)-BINOL, Ti(i-PrO)4, and 4-picolyl chloride hydrochloride, promoted the reaction smoothly to afford the corresponding alpha,beta-unsaturated delta-lactone derivatives in moderate-to-good yields (46-79%) with high enantioselectivities (up to 88% ee). Natural products (R)-(+)-kavain (70% ee, >99% ee after single recrystallization) and (S)-(+)-dihydrokavain (84% ee) were also prepared in one step by using this methodology.     

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).     

Asymmetric hydrogenation of itaconic acid and enol acetate derivatives with the Rh-TangPhos catalyst

[reaction: see text] The Rh-TangPhos catalyst has been used for asymmetric hydrogenation of itaconic acid and enol acetate derivatives. A variety of chiral 2-substituted succinic acids and chiral acetates have been obtained in excellent ee values (up to 99% ee).     

Asymmetric Suzuki-Miyaura cross-coupling of aryl chlorides with enhancement of reaction time and catalyst turnover

A series of new chiral phosphonite ligands were evaluated for the palladium-catalyzed asymmetric Suzuki-Miyaura cross-coupling reactions of aryl chlorides. Ligand 4 gave 91% yield and 78% ee with 0.5 mol % catalyst loading for the coupling of aryl boronic acid and aryl chloride in 5 h. When the catalyst loading was lowered to 0.1 mol % the same reaction gave 75% yield and 76% ee.     

Hydrogen bonding makes a difference in the rhodium-catalyzed enantioselective hydrogenation using monodentate phosphoramidites

A new generation of monodentate phosphoramidite ligands bearing a primary amine moiety was found to display comparable or better efficiency than bisphosphines in the Rh-catalyzed asymmetric hydrogenation of challenging substrates, such as (Z)-methyl alpha-acetoxyacrylate or (E)-beta-aryl itaconate derivatives, affording the corresponding hydrogenation products with excellent enantioselectivities (up to >99% ee). The presence of intermolecular hydrogen bonding (HB) between two monodentate ligands in the catalyst was found to be critical for excellent catalyst performance. This finding provides a basis for design and development of further catalyst systems using this type of monodentate phosphoramidite ligands.     

The Direct catalytic asymmetric cross-Mannich reaction: a highly enantioselective route to 3-amino alcohols and alpha-amino acid derivatives

The first proline-catalyzed direct catalytic asymmetric one-pot, three-component cross-Mannich reaction has been developed. The highly chemoselective reactions between two different unmodified aldehydes and one aromatic amine are new routes to 3-amino aldehydes with dr>19:1 and up to >99 % ee. The asymmetric cross-Mannich reactions are highly syn-selective and in several cases the two new carbon centers are formed with absolute stereocontrol. The reaction does not display nonlinear effects and therefore only one proline molecule is involved in the transition state. The reaction was also catalyzed with good selectivity by other proline derivatives. The Mannich products were converted into 3-amino alcohols and 2-aminobutane-1,4-diols with up to >99 % ee. The first one-pot, three-component, direct catalytic asymmetric cross-Mannich reactions between unmodified aldehydes, p-anisidine, and ethyl glyoxylate have been developed. The novel cross-Mannich reaction furnishes either enantiomer of unnatural alpha-amino acid derivatives in high yield and up to >99 % ee. The one-pot, three-component, direct catalytic asymmetric reactions were readily scaled up, operationally simple, and conductible in environmentally benign and wet solvents. The mechanism and stereochemistry of the proline-catalyzed, one-pot, three-component, asymmetric cross-Mannich reaction are also discussed.     

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.     

Pd(II) complexes of monodentate deoxycholic acid derived binaphthyl diamido phosphites as chiral catalysts in the asymmetric Suzuki-Miyaura cross-coupling

Chiral binaphthyl diamidophosphites derived from deoxycholic acid were synthesized and used as ligands for the preparation of mononuclear Pd(II) complexes, which were employed as catalysts in the asymmetric Suzuki-Miyaura cross-coupling of arylboronic acids with aryl bromides. Among the different reaction parameters, the substrate concentration emerged as being crucial for the outcome of the reaction: the reaction was faster in a concentrated reaction mixture, and could be performed at 0 °C, where the reaction promoted by the Pd-complexes was more enantioselective affording cross-coupling products with ee up to 70%.     

SpirOP, DPAMPP和不对称催化反应

设计和合成了新型手性配体SpirOP和DPAMPP,它们与铑配位形成阳离子型手性催化剂,在催化脱氢氨基酸的不对称氢化反应中,显示出高催化活性和对映选择性,其ee值高达99%。     

New C2-symmetric chiral phosphinite ligands based on amino alcohol scaffolds and their use in the ruthenium-catalysed asymmetric transfer hydrogenation of aromatic ketones

Asymmetric transfer hydrogenation processes of ketones with chiral molecular catalysts are attracting increasing interest from synthetic chemists due to their operational simplicity. C₂-symmetric catalysts have also received much attention and been used in many reactions. A series of new chiral C₂-symmetric bis(phosphinite) ligands has been prepared from corresponding amino acid derivated amino alcohols or (R)-2-amino-1-butanol through a three- or four-step procedure. Their structures have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. ¹H-³¹P NMR, DEPT, ¹H-¹³C HETCOR or ¹H-¹H COSY correlation experiments were used to confirm the spectral assignments. In situ prepared ruthenium catalytic systems were successfully applied to ruthenium-catalyzed asymmetric transfer hydrogenation of acetophenone derivatives by iso-PrOH. Under optimized conditions, these chiral ruthenium catalyst systems serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and act as good catalysts, giving the corresponding optical secondary alcohols in 99% yield and up to 79% ee.