Showing papers in "Tetrahedron-asymmetry in 2008"

Recent advances in enantioselective trifluoromethylation reactions

Abstract: Fluorinated organic compounds have received considerable attention because they possess unique properties such as greater stability, higher electronegativity, and water and oil repellency, which are potentially beneficial in terms of the development of novel pharmaceutical agents and advanced materials. Such extreme behaviors of fluoro-organic compounds however, often make their syntheses all the more complicated, especially when the synthesis of target compounds requires an enantiocontrolled methodology. Many strategies can be employed for introducing chirality into organic molecules, but enantioselective fluorination and trifluoromethylation reactions are especially attractive because non-fluorinated prochiral substrates can be directly transformed to chiral fluoro-organic compounds with a control of absolute configuration. Significant progress has been made in the development of the asymmetric fluorination reaction in recent years; however, the direct enantioselective trifluoromethylation reaction remains a challenge. In this report, we discuss recent developments in the enantioselective trifluoromethylation reactions, including nucleophilic, electrophilic, and radical approaches. Although the emphasis of this report is on the enantioselective trifluoromethylation reaction, the less-studied enantioselective difluoromethylation and monofluoromethylation reactions are also covered.

Advances in chiral ionic liquids derived from natural amino acids

Abstract: Ionic liquids (ILs) possess a number of unique properties; hence they have received much interest as green media for synthesis, analysis, catalysis, separation, and energy provision. More recently, chiral ionic liquids (CILs), which are derived from natural amino acids with chirality, biodegradability, reduced toxicity, and high biocompatibility, have also attracted interest. This report provides an overview of the design, synthesis, properties, and applications of these new CILs derived from natural amino acids. This is a current area of research that is poised for rapid development and expansion.

Stereoselective syntheses of quaternary substituted α-amino acids using oxazol-5-(4H)-ones

Abstract: Quaternary α-amino acids play vital roles in protein and synthetic chemistries. Stereoselective access to such molecules has been an intensive focus of research in recent years, and new methods are continuously being explored. The present mini-review gives an overview of stereoselective syntheses of quaternary α-amino acids produced from racemic oxazolones.

Strategies in optical resolution: a practical guide

Abstract: Despite the dramatic development of enantioselective synthesis and chromatographic separation methods, resolution still remains the most inexpensive and operationally simplest method for producing pure enantiomers on a large scale. No extreme conditions or expensive reagents are required and the expensive resolving agents can be eventually recovered. This review presents guidelines for selecting the optimal method for resolving a given racemate and is based mainly on the authors long experience in the resolution of industrially important molecules. Methods for predicting the efficiency of the resolution based on the analysis of physico-chemical properties of the reactants are also described.

Synthesis of enantiopure triazolium salts from pyroglutamic acid and their evaluation in the benzoin condensation

Abstract: A family of enantiopure 1,2,4-triazolium salts were prepared starting from the inexpensive (S)-pyroglutamic acid. After treatment with base, the corresponding N-heterocyclic carbenes were tested as organocatalysts in the asymmetric benzoin condensation and gave good yields and up to 95% ee.

Enantioselective synthesis of naphthopyran derivatives catalyzed by bifunctional thiourea-tertiary amines

Abstract: An efficient bifunctional thiourea catalyzed addition–cyclization reaction of 2-naphthol with α,α-dicyanoolefins is realized under mild conditions to afford the corresponding naphthopyran derivatives in high yields and moderate enantioselectivities. Additionally, the development of an asymmetric three-component one-pot procedure for the synthesis of naphthopyran derivatives is also reported.

Enantiomer selective acylation of racemic alcohols by lipases in continuous-flow bioreactors

Abstract: Continuous-flow mode enantiomer selective acetylations of racemic 1-phenylethanol, 1-cyclohexylethanol, and 1-phenylpropan-2-ol ( rac - 1a – c , respectively) with vinyl acetate were performed in small stainless steel packed-bed reactors filled with different commercial lipase preparations. In several lipase-filled columns, highly enantiomer selective ( E > 100) kinetic resolutions of these alcohols were achieved. In most cases, comparison of the continuous-flow and batch mode (shake flask) biotransformations indicated similar enantiomer selectivities ( E ) but higher productivities (specific reaction rate: r ) in the corresponding continuous-flow reaction. The effect of temperature (0–60 °C) and pressure (1–120 bar) on the continuous-flow acetylation of racemic 1-phenylpropan-2-ol was investigated in an immobilized Candida antarctica lipase B (CaLB) filled reactor. Pressure had no significant effect on r and E . Expectedly, a monotonous increase of specific reaction rate ( r ) was observed within this temperature range. Most surprisingly, the enantiomer selectivity had a maximum ( E ∼ 25, at 20 °C) and a minimum ( E ∼ 7, at 50 °C). The continuous-flow reactions in CaLB-filled columns were successfully applied for preparative scale kinetic resolutions of rac - 1a – c .

Recent advances in the stereoselective synthesis of trans-3,4-disubstituted-piperidines : applications to (-)-paroxetine

Abstract: Piperidine ring systems are the key structural elements in a vast array of natural products as well as in a large class of biologically active natural products, being also often embedded within scaffolds recognized as privileged structures by medicinal chemists. Accordingly, new stereoselective routes to substituted piperidines are of widespread interest. An overview of the asymmetric synthetic routes to trans -3,4-disubstituted piperidines, featuring the substitution pattern of (−)-paroxetine [(3 S ,4 R )-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine], a well-known selective serotonin reuptake inhibitor (SSRI) used worldwide as an antidepressant in humans, is presented. This review is mainly focused on the enantioselective routes to (−)-paroxetine, which has become a very popular synthetic target to test the efficiency of new methodologies. Some recent stereoselective approaches to the racemic compound are also included.

Chiral catalysts for the asymmetric cycloaddition of carbon dioxide with epoxides

Abstract: Several chiral BINADCo(III)X (BINAD = Bis(1,1′-2-hydroxy-2′-alkoxy-3-naphthylidene)-1,2-cyclohexanediamine, X = OAc, CF3CO2, CCl3CO2, OTs, p-NO2PhCO2) complexes were synthesized and used to catalyze the asymmetric cycloaddition of carbon dioxide with epoxides under mild condition to afford chiral cyclic carbonates. The best catalyst of (S,S,S,S)-BINADCo(III)(OAc) 9b and phenyltrimethylammonium tribromide (PTAT) can provide propylene carbonate with the highest ee being 95% at −20 °C.

Convenient enantioselective synthesis of β-trifluoromethyl-β-aminoketones by organocatalytic asymmetric Mannich reaction of aryl trifluoromethyl ketimines with acetone

Abstract: The l -proline-catalyzed asymmetric Mannich reaction has been performed between aryl trifluoromethyl ketimines and acetone to provide, for the first time, chiral β-aryl-β-trifluoromethyl-β-aminoketones in high yields and with 74–92% enantiomeric excesses.

Protonated ( S )-prolinamide derivatives—water compatible organocatalysts for direct asymmetric aldol reaction

Abstract: Protonated chiral (S)-prolinamide derivatives have been developed as water compatible highly efficient organocatalysts for a direct enantioselective aldol reaction. A simple protonated (S)-prolinamide organocatalyst prepared from l -proline and 3-nitroaniline catalyzes the aldol reaction of unmodified ketones and a variety of aromatic aldehydes yielding aldol product in high yield with enantioselectivities of up to 98% and diastereoselectivity of up to >99:1.

Organocatalyzed Friedel–Craft-type reaction of 2-naphthol with β,γ-unsaturated α-keto ester to form novel optically active naphthopyran derivatives

Abstract: A novel bifunctional thiourea–tertiary-amine-catalyzed enantioselective Friedel–Craft-type addition reaction of 2-naphthol with β,γ-unsaturated α-keto ester was developed. Subsequent dehydration of the reaction adducts with a catalytic amount of concentrated H2SO4 in a one-pot fashion readily afforded a series of new optically active naphthopyran derivatives with moderate to good yields (up to 91%) and enantioselectivities (up to 90%).

Asymmetric bioreduction of α,β-unsaturated nitriles and ketones

Abstract: Two applications for the asymmetric reduction of activated alkenes employing isolated enoate reductases are reported. A series of α,β-unsaturated nitriles were shown to be converted to the optically active nitrile products in high yields and excellent enantioselectivities (up to 99% ee). In addition, the reduction of 2,3-disubstituted cyclopentenones was shown to provide almost exclusively trans -2,3-disubstituted cyclopentanones in high yield and enantiopurity (94% ee).

Asymmetric Henry reaction catalyzed by a copper tridentate chiral schiff-base complex

Abstract: A series of copper-tridentate chiral Schiff-base complexes were prepared and employed in an asymmetric Henry reaction, affording the corresponding adducts in good yields and with high enantioselectivities (up to 96% ee).

Per-6-amino-β-cyclodextrin catalyzed asymmetric Michael addition of nitromethane and thiols to chalcones in water

Abstract: An environmentally benign and enantioselective Michael addition of nitromethane/thiols to trans-chalcone catalyzed by per-6-amino-β-cyclodextrin (per-6-ABCD) is carried out in water at room temperature with good yield and enantiomeric excess. The catalyst is recovered and reused without loss in its activity.

Asymmetric reduction of aryl imines using Candida parapsilosis ATCC 7330

Abstract: A highly enantioselective one pot, novel biocatalytic method for the asymmetric reduction of aryl imines is reported. Treatment of aryl imines with Candida parapsilosis ATCC 7330 in aqueous medium produces the enantiomerically pure ( R )-secondary amines in moderate to good yields (55–80%) with excellent enantiomeric excesses (95–>99%).

Asymmetric Henry reaction catalyzed by chiral secondary diamine-copper(II) complexes

Abstract: The enantioselective Henry reaction was efficiently carried out under mild reaction conditions in 96% ethanol. The chiral C 2 -symmetric, secondary bisamines based on the 1,2-diaminocyclohexane framework and copper(II) acetate were found to promote the asymmetric nitroaldol reaction. Aromatic and aliphatic aldehydes were reacted with nitromethane to provide the corresponding β-nitroalcohols in very good yields and enantioselectivities up to 94%.

Direct asymmetric three-component Mannich reactions catalyzed by a siloxy serine organocatalyst in water

Abstract: A siloxy- l -serine organocatalyst has been developed to catalyze the asymmetric three-component Mannich reactions in the presence of water via a biphasic system, furnishing the Mannich products in good yields and high enantioselectivities.

New pyrrolidine-triazole-based C2 symmetric organocatalysts and their utility in the asymmetric Michael reaction of β-nitrostyrenes and the synthesis of nitrochromenes

Abstract: The synthesis of new C2 symmetric bis(pyrrolidine-triazole)-based organocatalysts and their utility in the asymmetric Michael reaction of β-nitrostyrenes with very high diastereo- and enantioselectivity in water without any additives is reported. The asymmetric synthesis of nitrochromenes is also illustrated.

A mild and efficient procedure for asymmetric Michael additions of cyclohexanone to chalcones catalyzed by an amino acid ionic liquid

Abstract: A mild and efficient procedure for Michael additions of cyclohexanone to chalcones has been developed. In the presence of amino acid ionic liquid [EMIm][Pro] (200 mol %), cyclohexanone reacted with various chalcones to afford Michael adducts in high yields (85–98%) and moderate to good enantioselectivities (16–94% ee), accompanied by an unexpected solvent-dependent inversion of the enantioselectivity.

Calixarene-based chiral phase-transfer catalysts derived from cinchona alkaloids for enantioselective synthesis of α-amino acids

Abstract: The synthesis of the first calixarene-based chiral phase-transfer catalysts derived from cinchona alkaloids has been achieved in two steps from p-tert-butylcalix[4]arene. The catalytic efficiency of the chiral calix[4]arenes 3a–c was evaluated by carrying out the phase-transfer alkylation of N-(diphenylmethylene)glycine ethyl ester with benzyl bromide. Various factors that affect the chemical yield and enantioselectivity were also examined. Benzylation of glycine imine 4 using calix[4]arene-based dimeric catalyst 3a as a chiral phase-transfer catalyst in toluene/CHCl3 mixture (7:3 v/v) at 0 °C gave the best enantioselectivities and yields in the presence of aqueous NaOH.

Novel carbohydrate-based chiral ammonium ionic liquids derived from isomannide

Abstract: This report describes the synthesis and characterization of novel carbohydrate-based chiral ammonium ionic liquids using isomannide as a biorenewable substrate. The diastereomeric interactions of these chiral ammonium ionic liquids with racemic Mosher’s acid salt have been studied using NMR, which indicates their participation in chiral discrimination and shows their potential applications in chiral resolution.

Enantioselective synthesis of polysubstituted prolines by Binap-silver-catalyzed 1,3-dipolar cycloadditions

Abstract: This work has been supported by the DGES of the Spanish Ministerio de Educacion y Ciencia (MEC) (Consolider INGENIO 2010 CSD2007-00006, CTQ2007-62771/BQU, and CTQ2004-00808/BQU), Generalitat Valenciana (CTIOIB/2002/320, GRUPOS03/134 and GV05/144), and by the University of Alicante. M.G. Retamosa thanks the University of Alicante for a predoctoral fellowship.

Alternative and complementary approaches to the asymmetric synthesis of C3 substituted NH free or N-substituted isoindolin-1-ones

Abstract: Complementary synthetic approaches to enantiomerically pure C3 alkylated or arylated NH free or N-substituted isoindolinones have been developed. The key step is elaboration of diversely substituted 2-alkyl- and arylbenzylamines, which can be submitted to a bis-metallation process followed by interception with a carbonylating agent. They can be also converted into N -alkylbromobenzylcarbamates or into bromobenzyldicarbamates and the assembly of the titled compounds can be readily ensured by reliance upon the Parham cyclization process.

Highly stereoselective Pictet–Spengler reaction of d-tryptophan methyl ester with piperonal: convenient syntheses of Cialis (Tadalafil), 12a-epi-Cialis, and their deuterated analogues

Abstract: The acid-catalyzed Pictet–Spengler reaction of d -tryptophan methyl ester with piperonal in acetic acid has been reported, the best stereoselectivity (cis/trans = 92:8) was obtained with benzoic acid as the catalyst. The Pictet–Spengler reaction of d -tryptophan methyl ester hydrochloride with piperonal in various solvents has been extensively studied, the solvent-dependence of stereoselectivities could be principally attributed to the solubility-difference between cis and trans products 5-HCl in the used solvent, the best stereoselectivity (cis/trans = 99:1) was obtained using nitromethane or acetonitrile as the solvent. A base-catalyzed epimerization at 12a-position of Cialis 1 (tadalafil) in a DMSO-containing solvent was also exploited. Cialis, 12a-epi-Cialis 2, deuterium-labeled 3,3,12a-d3-Cialis 3, and 3,3,12a-d3-12a-epi-Cialis 4 were efficiently synthesized from d -tryptophan methyl ester hydrochloride.

Chiral palladium-pincer complex catalyzed asymmetric condensation of sulfonimines and isocyanoacetate

Abstract: This thesis is focused on the development of new pincer complex-catalyzed transformations. Optimization of the catalytic properties (fine-tuning) was directed to increase the catalytic activity as well as the chemo-, stereo- and enantioselectivity of the complexes. This was achieved by varying the heteroatoms in the terdentate pincer ligand, by changing the electronic properties of the coordinated aryl moiety and by implementing chiral functionalities in the pincer complexes. In the cross-coupling reaction of vinyl epoxides and aziridines with organoboronic acids the chemoselectivity of the reaction could be increased by employment of pincer complexes instead of commonly used Pd(0) catalysts. Furthermore, the introduction of a methoxy substituent in the aromatic subunit of the complex considerably increased the activity of the pincer complex catalyst. Fine-tuning of the enantioselectivity in electrophilic allylation reactions was achieved by using a wide variety of new BINOL- and biphenanthrol-based pincer complexes. The highest enantioselectivity (85% ee) was obtained by applying biphenanthrol-based pincer complexes. Stereoselective pincer complex-catalyzed condensation of sulfonylimines with isocyanoacetate could be achieved under mild reaction conditions. By application of chiral PCP catalysts, 2-imidazolines could be obtained with up to 86% ee. A new pincer complex-catalyzed C-H bond functionalization based reaction between organonitriles and sulfonylimines affords homoallylic amines and beta-aminonitriles in high yields. The asymmetric version of this process affords beta-aminonitriles with up to 71% ee. In the last chapter, a pincer complex-catalyzed redox coupling reaction is described. In this highly regio- and stereoselective process the integrity of the pincer catalysts is fully retained. This catalytic reaction proceeds with a high level of functional group tolerance, as allylic acetate and aryl halide functionalities are retained.

Silica-supported pyrrolidine–triazole, an insoluble, recyclable organocatalyst for the enantioselective Michael addition of ketones to nitroalkenes

Abstract: A highly efficient, silica-supported organocatalyst for the Michael addition of ketones to nitroalkenes is successfully developed. A 1,2,3-triazole ring, constructed via a click 1,3-dipolar cycloaddition, plays a dual role of grafting the chiral pyrrolidine onto the silica surface and of providing a structural element complementary to the pyrrolidine. The supported catalyst demonstrated high activity and enantioselectivity; furthermore, it can be readily reused four times without significant loss of catalytic activity.

Ruthenium(II) and rhodium(III) catalyzed asymmetric transfer hydrogenation (ATH) of acetophenone in isopropanol and in aqueous sodium formate using new chiral substituted aromatic monosulfonamide ligands derived from (1R,2R)-diaminocyclohexane

Abstract: A series of aromatic monosulfonamide ligands derived from (1 R ,2 R )-diaminocyclohexane were synthesized with electron withdrawing and donating groups. These were complexed with Rh(Cp ∗ ) or Ru(arene) and their catalytic efficiencies were compared in the ATH of acetophenone using sodium formate/water or isopropanol/KOH as the hydrogen source. Results suggest that substituents on the benzene ring of the sulfonamide have very little electronic impact on the enantioselectivity and mechanism of the reaction.

Synthesis of highly enantiomerically enriched amines by the diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines

Abstract: The reaction of triorganozincates with (R)-N-(tert-butanesulfinyl) imines gives the expected α-branched sulfinamides in good to excellent yields with diastereomeric ratios of up to 98:2. The N-sulfinyl group of the products can be easily removed by acidic treatment, affording the corresponding chiral primary amines in enantiomeric excesses of up to 96%. The reactivity and the selectivity shown by the triorganozincates are different from the ones observed with the corresponding Grignard reagents, which allows, in several cases, the preparation of both enantiomers of an amine from the same imine substrate. When mixed triorganozincates are used, one can take advantage of the slow transfer rate of the methyl group to use it as a non-transferable one. Both aromatic and aliphatic aldimines, as well as activated ketimines, are good substrates for these addition reactions.

Asymmetric transfer hydrogenation of ketones with a polyethylene glycol bound Ru catalyst in water

Abstract: A new polyethylene glycol supported Ru catalyst was synthesized and applied in the asymmetric transfer hydrogenation of various aromatic ketones in water with high chemical yields and enantioselectivities without adding any surfactants. The catalyst could be easily recycled several times without a significant loss of enantioselectivity and activity.