Asymmetric Henry reaction catalyzed by C2-symmetric tridentate bis(oxazoline) and bis(thiazoline) complexes: metal-controlled reversal of enantioselectivity

[reaction: see text] C(2)-symmetric tridentate bis(oxazoline) and bis(thiazoline) ligands with a diphenylamine backbone have been investigated in the catalytic asymmetric Henry reaction of alpha-keto esters with different Lewis acids. Their Cu(OTf)(2) complexes furnished S enantiomers, while Et(2)Zn complexes afforded R enantiomers, both of them with higher enantioselectivities (up to 85% ee). Reversal of enantioselectivity in asymmetric Henry reactions was achieved with the same chiral ligand by changing the Lewis acid center from Cu(II) to Zn(II). The results show that the NH group in C(2)-symmetric tridentate chiral ligands plays a very important role in controlling both the yields and enantiofacial selectivity of the Henry products.     

Asymmetric Michael addition reactions of 2-silyloxyfurans catalyzed by binaphthyldiimine-Ni(II) complexes

N,N'-Bis(2-quinolylmethylene)-1,1'-binaphthyl-2,2'-diamine-Ni(II) complex and analogous complexes were found to be efficient chiral Lewis acid catalysts for the asymmetric Michael addition reactions between 2-silyloxyfurans and 3-alkenoyl-2-oxazolidinones, for which asymmetric inductions of up to 97% ee were obtained.     

Recoverable salen-based macrocyclic chiral complexes; catalysts for enantioselective Henry reactions

Cobalt and chromium complexes have been prepared from chiral calix–salen cyclic ligands. The corresponding tetrahydrosalen reduced forms have been used for copper salt complexation. These new chiral catalysts have been tested for their ability to promote asymmetric Henry reactions between various aldehydes and nitromethane under heterogeneous conditions. The best results were obtained by using tetrahydrosalen-based copper macrocycles, in terms of activity, selectivity, and stability during the recycling process. Ten consecutive runs could indeed be performed with the same catalyst batch to produce the target 1-(2-methoxy-phenyl)-2-nitro-ethanol with highly stable values in terms of yield and enantioselectivity (up to 94% ee).     

Catalytic effect and recyclability of imidazolium-tagged bis(oxazoline) based catalysts in asymmetric Henry reactions

Functional imidazolium ionic liquids have been developed as a new class of versatile catalysts. C(2)-symmetric imidazolium-tagged bis(oxazoline) ligands were prepared, and the anions of the ligands were altered. The catalysts based on the new ligands and Cu(OAc)(2)·H(2)O were applied in asymmetric Henry reactions between various aldehydes 3 and CH(3)NO(2)4. The catalysts achieved a high level of enantioselectivity; product (R)-5n was attained at 94% ee in MeOH. Moreover, the catalyst could be recycled 6 times without an obvious loss of activity or enantioselectivity. In addition, a theoretical mechanistic study was conducted to explain the origin of the enantioselectivity.     

Asymmetric Henry reaction catalyzed by oxazolinyl Cu(II) complexes

A novel family of oxazolinyl copper(II) catalysts have been developed and used as Lewis acid catalysts in the asymmetric Henry reaction of various aldehydes with nitromethane. The corresponding nitroalcohol products were obtained in moderate yields (40–80%) and with moderate enantioselectivity (10–40% ee).     

Enantiocatalytic activity of substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-one ligands

Currently, asymmetric synthesis represents one of the main streams of organic synthesis. Although an extensive research has been carried out in this area, the synthesis of chiral compounds with the required enantiomeric purity is still a challenging issue. Herein, we focus on the preparation of new enantioselective catalysts based on pyridine-imidazolidinones. The substituted 5-benzyl-2-(pyridine-2-yl)imidazolidine-4-ones 5–8 were prepared by condensation of chiral amino acid amides (α-methylDOPA and α-methylphenylalanine) with 2-acetylpyridine and pyridine-2-carbaldehyde. The individual isomers of the described ligands 5–8 were separated chromatographically. The copper(II) complexes of these chiral ligands were studied as enantioselective catalysts for the asymmetric Henry reaction of substituted aldehydes with nitromethane or nitroethane. The ligands containing a methyl group at the 2-position of the imidazolidinone ring 6a and 8a exhibit a high degree of enantioselectivity (up to 91% ee). The nitroaldols derived from nitroethane (2-nitropropan-1-ols) were obtained with a comparable enantiomeric purity to derivatives of 2-nitroethanol. This group of ligands represents a new and promising class of enantioselective catalysts, which deserve further attention.     

Highly enantioselective nitroaldol reactions catalyzed by copper(II) complexes derived from substituted 2-(pyridin-2-yl)imidazolidin-4-one ligands

Ten optically pure substituted 2-(pyridin-2-yl)imidazolidin-4-ones, 1a-d, 2a-4a, and 2b-4b, were prepared and characterized. The absolute configurations of individual ligands were determined by X-ray analysis or NOESY experiments. The Cu(II) complexes of the respective ligands were studied as enantioselective catalysts of the nitroaldol (Henry) reaction of aldehydes with nitromethane, giving the corresponding substituted 2-nitroalkanols. In the case of an anti arrangement of the imidazolidin-4-one ring, the obtained result was 91-96% ee, whereas in the case of syn arrangement, a significant drop to 25-27% ee was observed.     

Chiral copper-Schiff base catalyst for asymmetric henry reaction

Five copper-Schiff base complexes were synthesized conveniently from copper(II) acetate monohydrate, salicylaldehydes, and amino alcohols. The complexes were shown to be effective as catalysts in the asymmetric Henry reaction affording nitro alkanols in up to 98% yield with moderate and good enantiomeric excess (up to ee 38.6%). Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 12, pp. 1754–1755. The text was submitted by the authors in English.     

A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-d-arabinitol using Co(III)(salen)-catalyzed hydrolytic kinetic resolution of a two-stereocentered anti-azido epoxide

A concise enantioselective synthesis of 1,4-dideoxy-1,4-imino-d-arabinitol, (+)-DAB-1, has been described in good overall yield (18.1%) and with high enantiomeric purity (up to 98% ee) starting from a simple raw material, cis-2-butene-1,4-diol. The Co-catalyzed hydrolytic kinetic resolution of a two-stereocentered racemic azido epoxide followed by asymmetric dihydroxylation of the alkene and ‘one pot’ reductive cyclisation of the azido diol are key reactions in the synthetic sequence.     

Promotion of Henry reactions using Cu(OTf)2 and a sterically hindered Schiff base: access to enantioenriched β-hydroxynitroalkanes

The steric and electronic properties of chiral Schiff base ligands derived from cinchona alkaloids were evaluated in asymmetric Henry reactions. Amongst these, the sterically hindered ligand 2 showed outstanding catalytic efficiency in the Cu(II) catalyzed asymmetric addition of nitroalkanes to a variety of aldehydes to afford the desired adducts in high yields (up to 97%) with excellent enantioselectivities (up to 99% ee) and moderate to good diastereoselectivities (up to 84:16 dr).     

A class of α-amino acids-derived multifunctional amidophosphane precatalysts: application to the highly enantio- and diastereoselective silver(I)-catalyzed 1,3-dipolar cycloaddition reaction

A class of multifunctional amidophosphanes derived from chiral α-amino acids have been developed with two amide bonds, a tertiary amine and a phosphine. In combination with Ag(I) salts, these amidophosphanes have been demonstrated as highly efficient multifunctional catalysts in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides as well as the three-component reaction of the α-iminoesters in situ generated. Under optimal conditions, highly functionalized endo-8 pyrrolidines were obtained with good to excellent yields (up to 99% yield) and enantioselectivities (up to 98% ee).     

Synthesis and Application of Novel Chiral Poly-nuclear-Mn(Ⅲ) Catalysts on Asymmetric Epoxidation of Alkenes

The interest of the coordination chemistry of manganese has been driver by the important roles of metalloenzymes and highly valuable catalysts in olefin expoxidation.1 Jacobsen Salen-Mn complexes with a simple structure have been commercially utilized to catalyze asymmetric epoxidation of unfunctionalized cis-alkenes2, but the catalytic enantioselectivity for trans-alkenes, unfortunately, are lower and this kinds of complexes are unstable and difficult to be recovered for reuse.3 In order to improve the catalytic activity and recyclability, many new catalysts including the supported catalysts,heterogeneous catalysts and else modified catalysts have been studied, however their comprehensive effects are unsatisfying.4Recently, some studies in interrelated realm showed that the catalytic performance of bi- or poly-nuclear complexes was superior to that of monomer.5 Meanwhile, our previous studies also showed that properly increasing the molecular weight of catalysts as well as the extent of conjugation of active center would not only result in high activity or reactivity but also its stability and recyclablity, aiding product isolation and catalyst recovery.6For these reasons we designed and synthesized the chiral poly-Mn(Ⅲ) complexes in which active sites were conjugated in certain distance side by side though central nucleus of 4, 6-dihydroxy- isophthalaldehyde (see the scheme). These novel Mn(Ⅲ) complexes have been investigated for the first time as catalysts (lmol%)for the asymmetric epoxidation of alkenes by using pure urea-H2O2 as oxidant and NH4OAc as additive in CH2Cl2/MeOH, showing high activity and good enantioselectivity. All reactions were finished in 1.5h. Rather surprisingly, a marginal increase in ee was observed when the concentration of the substrate was increased from 0.01 to 0.5M. The poly-nuclear complex formation enhanced the catalyst's reactivity and stability. It, unlike mononuclear, could be easily recovered and reused several cycles with a decline of yield but a keep of ee's.A low concentration requirement of catalyst, high ee and chemical activity, mild reaction conditions and catalytic recycles render the kinds of complexes attractive.     

Synthesis of fluorine-substituted [2.2]paracyclophane-based carbene precursors for copper-catalyzed enantioselective boration of α,β-unsaturated ketones

Fluorine-substituted [2.2]paracyclophane-based carbene precursors have been successfully synthesized and applied to copper-catalyzed asymmetric β-boration of α,β-unsaturated ketones. Fluorination of the planar chiral carbenes has a beneficial impact on the catalytic performance of the relevant complexes. A variety of chiral β-boryl ketones were obtained in excellent yields (up to 99%) and with high enantioselectivities (up to 99% ee).     

Synthesis,copper(II) complexes and catalytic activity of substituted 6-(1,3-oxazolin-2-yl)pyridine-2-carboxylates

The optically pure 6-(4-alkyl-4,5-dihydro-1,3-oxazol-2-yl)pyridine-2-carboxylates have been prepared from 6-methoxycarbonylpyridine-2-carboxylic acid by a sequence of three reactions with the overall yield of 40–50%. Some of these compounds form stable complexes with Cu(II) ions in non-aqueous medium. Their polymeric structure was determined in the solid phase by X-ray diffraction analysis. The Cu(II) complexes were also used as catalysts for addition reactions of terminal alkynes to imines giving substituted propargylamines with maximum yield 64% and 37% ee.     

Asymmetric cyclopropanation catalyzed by C2-symmetric bis-(ephedrine)-Cu(II) complexes

The asymmetric cyclopropanation of styrene with alkyl diazoacetate was performed with a series of Cu(II) complexes of novel chiral ligands, which were derived from substitution of 1,3-dibromopropane, 1,2-dibromoethane, α,α′-dibromo-m-xylene and 2,6–bis(bromomethyl)pyridine with 1R, 2S-(−)-ephedrine. These prepared catalysts shown to be highly active in the enantioselective cyclopropanation with ee higher than 89% under the optimal conditions.     

d-Mannitol-derived novel chiral thioureas: Synthesis and application in asymmetric Henry reactions

Five novel thioureas have been obtained through multi-step reactions from d-Mannitol as starting material and applied as catalysts in the asymmetric Henry reaction. Using catalyst 7a, (1S,2R)-2-nitro-1-phenylpropan-1-ol containing two chiral centers was obtained in high yield and with high selectivity (up to 95% yield, 87% ee, 91:9 dr). This catalyst also retained activity in the presence of water, affording a up to 93% yield, 88% ee, and 94:6 dr.     

Use of copper(II)/diamine catalysts in the desymmetrisation of meso-diols and asymmetric Henry reactions: comparison of (−)-sparteine and (+)-sparteine surrogates

Four new copper(II)/diamine complexes comprising some (+)-sparteine surrogates and a cyclohexane-derived diamine were prepared and evaluated as chiral catalysts in desymmetrisation of meso-diols and asymmetric Henry reactions. Mono-benzoylation reactions generated two products with high enantioselectivity (90:10 to 97:3 er). Asymmetric Henry reactions gave nitro alcohols in 90:10 to 98:2 er. Notably, the sense of induction with the (+)-sparteine surrogates was opposite to that obtained using the copper(II)/(−)-sparteine complex. One of the nitro alcohol products was utilised in a concise synthesis of a chiral morpholine.     

Asymmetric induction afforded by chiral azolylidene N-heterocyclic carbenes (NHC) catalysts

Screening studies of new chiral imidazolium and triazolium based NHC salts I–VIII as ligands in asymmetric organometallic catalysis and as organocatalysts showed that these catalysts efficiently promoted the reactions. Moderate enantioselectivities (55–57% ee) were obtained in the asymmetric Cu-NHC catalysed conjugate additions of diethylzinc to cyclohexenone, in accordance with most previous studies. The chiral induction afforded in the gold(I)-NHC catalysed cyclopropanation reactions was low (<28% ee). However, these results represent the first reported chiral gold(I)-NHC catalysed olefin cyclopropanation. The NHC-organocatalysed asymmetric cross-annulation of cinnamaldehyde and trifluoroacetophenone gave lower enantioselectivity (<50% ee) but higher yields of the γ-lactone product relative to previous reports. The enantioselectivities obtained varied considerably, even within a group of structurally closely related NHCs. This study demonstrates the challenge of designing NHCs with a general ability to induce asymmetry in a broader range of reactions.     

Copper(II)‐Catalyzed Nitroaldol (Henry) Reactions: Recent Developments

Self‐assembled copper(II) complexes are described as effective catalysts for nitroaldol (Henry) reactions on water. The protocol involves a heterogeneous process and the catalysts can be recovered and recycled without loss of activity. Further, C2‐symmetric N,N′‐substituted chiral copper(II) salan complexes are found to be more effective catalysts than chiral copper(II) salen complexes for reactions in homogeneous catalysis, with high enantioselectivities. The reactions involve bifunctional catalysis, bearing the properties of a Brønsted base, as well as a Lewis acid, to effect the reaction in the absence of external additives.     

Isosteric expansion of the structural diversity of chiral ligands: Design and application of proline-based N,N′-dioxide ligands for copper-catalyzed enantioselective Henry reactions

Chiral N,N′-dioxide catalysts were designed based on isosteric approach. Using l-Proline as the starting material, a variety of chiral N,N′-dioxide ligands were obtained via conventional functional group transformations and were utilized in asymmetric Henry reactions between nitromethane and aromatic aldehydes. Using the N,N′-dioxide-copper(II) complexes as the catalysts, asymmetric Henry reaction produced the corresponding β-nitroalcohols in up to 66% yields and up to 83% ee's under mild conditions. The reactions were easy to carry out, and special care such as air or moisture-free conditions was not required.