Solid-liquid Phase-transfer Conditions Research Articles

Synthesis of α-d-galactose-based azacrown ethers and their application as enantioselective catalysts in Michael reactions

Crown ethers derived fromd-galactose generated good to excellent enantioselectivities in a few Michael reactions under solid–liquid phase transfer conditions.

Stereoselective Synthesis of Unsaturated and Functionalized l-NHBoc Amino Acids, Using Wittig Reaction under Mild Phase-Transfer Conditions

The stereoselective synthesis of a new amino acid phosphonium salt was described by quaternization of melting triphenylphosphine with the γ-iodo NHBoc-amino ester, derived from L-aspartic acid. The deprotection of the carboxylic acid function to afford the phosphonium salt with a free carboxylic acid group was achieved by a palladium-catalyzed desallylation reaction. This phosphonium salt was used in the Wittig reaction with aromatic or aliphatic aldehydes and trifluoroacetophenone, under solid-liquid phase-transfer conditions in chlorobenzene and in the presence of K(3)PO(4) as weak base, to afford the corresponding unsaturated amino acids without racemization. Thus, the reaction with substituted aldehydes allows to graft various functionalized groups on the lateral chain of the amino acid, such as trifluoromethyl, cyano, nitro, ferrocenyl, boronato, or azido. In addition, the reaction of the amino acid Wittig reagent with α,β-unsaturated aldehydes leads to amino acids bearing a diene on the lateral chain. Finally, this amino acid phosphonium salt appears to be a new powerful tool for the preparation of unsaturated and non-proteinogenic α-amino acids, directly usable for the synthesis of customized peptides.

Simultaneous C- and N-Alkylation of 2-Oxo-4,6-diaryl-1,2,3,4-tetrahydropyridine-3-carbonitrile Under Solid–Liquid Phase-Transfer Conditions

The alkylation of 2-oxo-4,6-diaryl-1,2,3,4-tetrahydropyridine-3-carbonitrile 1 has been carried out using different alkyl/arylating agents in solid–liquid phase-transfer catalysis conditions. The aim was to study the effect of steric hindrance offered by the aryl group in the sixth position of the pyridine ring on the ambient N- vs. O-alkylation ratio. Simultaneous C- and N-alkylation was encountered and confirmed by x-ray crystallography. Our study to gain exclusive regiocontrol for simultaneous alkylation was carried out. An alternative route for C‒C bond formation was also established by the removal of the cyano functionality.

Asymmetric Synthesis of α,α-Disubstituted α-Amino Acids via Enantioselective Alkylation of Azlactones under Biphasic Conditions Using P-Spiro Chiral Tetraaminophosphonium Salts as a Phase-Transfer Catalyst

Highly enantioselective alkylation of azlactones derived from α-amino acids has been achieved under solid-liquid phase-transfer conditions using P-spiro chiral tetraaminophosphonium salt as a catalyst. The resulting alkylated azlactones can be readily converted into the corresponding α,α-disubstituted α-amino acids through simple acidic hydrolysis.

Asymmetric catalysis of carbon–carbon bond forming reactions using amino acid-derived C1-symmetrical salen ligands

Four amino acids (alanine, valine, phenylalanine and phenylglycine) have been converted into C 1-symmetrical salen ligands and complexed to titanium, vanadium, copper and cobalt. The resulting complexes have been used as asymmetric catalysts for asymmetric cyanohydrin synthesis, asymmetric Strecker reactions, asymmetric synthesis of α-methyl amino acids and asymmetric Darzens condensations. Satisfactory levels of asymmetric induction were obtained from reactions in which the (salen)metal complex acts as a chiral Lewis acid, but low levels of asymmetric induction were obtained from reactions carried out under solid–liquid phase-transfer conditions.

N-Spiro Chiral Quaternary Ammonium Bromide Catalyzed Diastereo- and Enantioselective Conjugate Addition of Nitroalkanes to Cyclic α,β-Unsaturated Ketones under Phase-Transfer Conditions

[reaction, structure: see text] Conjugate addition of various prochiral nitroalkanes to cyclic alpha,beta-unsaturated ketones was found to be efficiently catalyzed by N-spiro C2-symmetric chiral quaternary ammonium bromide 1b possessing a 3,5-bis(3,4,5-trifluorophenyl)phenyl substituent under solid-liquid phase-transfer conditions to afford the corresponding gamma-nitro ketones in excellent chemical yields with unprecedented levels of diastereo- and enantiocontrol.

Asymmetric Phase-Transfer Catalyzed Glycolate Alkylation, Investigation of the Scope, and Application to the Synthesis of (−)-Ragaglitazar

[Reaction: see text]. Asymmetric glycolate alkylation using a protected acetophenone surrogate under solid-liquid phase-transfer conditions is a new approach to the synthesis of 2-hydroxy esters and acids. Diphenylmethyloxy-2,5-dimethoxyacetophenone 1 with a trifluorobenzyl cinchonidinium bromide catalyst 9 (10 mol %) and cesium hydroxide provided S-alkylation products 2 at -35 degrees C in high yield (80-99%) and with excellent enantioselectivities using a wide range of electrophiles (80-90% ee). Alkylated products were elaborated to useful alpha-hydroxy intermediates 3 using bis-TMS peroxide Baeyer-Villiger conditions and selective transesterification reactions. The ester products have been enantioenriched by simple recrystallization from ether to give a single isomer (99% ee). A tight ion-pair model is proposed for the observed S-stereoinduction that includes van der Waals contacts between the extended enolate and the isoquinoline of the catalyst. To demonstrate the utility of the new methodology, the anti-diabetes drug (-)-ragaglitazar 24 was synthesized in six steps from a key 2-alkoxy-3-p-phenoxypropionic acid 26 that was made using PTC glycolate alkylation.

Free Radical-Mediated Aryl Amination: A Practical Synthesis of (R)- and (S)-7-Azaindoline α-Amino Acid.

Two nonnatural proline derivatives, (S)- and (R)-7-azaindoline α-amino acid have been prepared and isolated as their trifluoroacetate salt on gram scale. The convergent sequence (6 steps from 2-bromopyridine) employs a combination of enantioselective phase transfer catalyzed glycine alkylation and free radical-mediated aryl amination. Implementation of the solid-liquid phase transfer conditions requires manual pulverization of cesium hydroxide, efficient mechanical stirring, and effective low temperature control. This large scale free radical cyclization protocol replaces benzene solvent with toluene without complication, and the crystalline nature of the intermediates and final product enables straightforward purification at each stage, including enantiomeric enrichment (89 to >99% ee for 4b).

Synthesis and Evaluation of Optically Pure Dioxolanes as Inhibitors of Hepatitis C Virus RNA Replication.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and evaluation of optically pure dioxolanes as inhibitors of hepatitis C virus RNA replication

A series of optically pure 1,3-dioxolane nucleoside mimics was synthesized by a synthetic route that allowed incorporation of a 5R-methyl substituent from commercially available starting materials. The pyrrolo[2,3-d]pyrimidine heterocycle was chosen as a substitute for the purine derivative. Coupling of the pyrrolo[2,3-d]pyrimidine and the dioxolane was performed under solid–liquid phase transfer conditions. The ability to inhibit HCV RNA replication was assessed in a cell based subgenomic replicon assay. None of the described compounds displayed significant anti-HCV activity.

Synthesis of novel bicycloalkane ring-fused pyridines via Michael addition reaction ofa,ß-Unsaturated Nitriles

Camphorylidene(cyano)thioacetamide (3) and camphorylidenemalononitrile (9) were easily prepared by the reaction of (+)-camphor (1) with cyanothioacetamide (2) and malononitrile (8), respectively, under solid-liquid phase-transfer catalyzed conditions. The reaction of the arylidene derivatives of malononitrile, cyanothioacetamide and cyanoacetamide with 3 and 9 leads to condensed 2-thioxo- and 2-oxo-pyridine derivatives. Treatment of the latter compounds with P4S10 causes transformation into the corresponding pyridinethiones.

Reaction of Amino Acid Salts with 4-Nitrophenyl Acetate under Solid-Liquid Phase Transfer Conditions

The reaction of amino acid salts with 4-nitrophenyl acetate in a system consisting of a solid phase and organic solvent with catalysis by crown ethers and quaternary onium salts may be carried out both on the phase separation surface and in the organic phase depending on the nature of the participants in the phase transfer catalysis reaction.

HETEROCYCLIZATION USING PHASE TRANSFER CATALYSIS: A SIMPLE AND CONVENIENT SYNTHESIS OF 2-AMINO-1-ARYL-5-OXO-4,5-DIHYDRO-1H-PYRROLE-3-CARBONITRILES

A simple and convenient synthesis of 2-amino-1-aryl-5-oxo-4,5-dihydro-1H-pyrrole-3-carbonitriles has been studied with and without phase transfer conditions. The best results were obtained using 18-crown-6 under solid-liquid phase transfer conditions in acetonitrile.

Aromatic nucleophilic fluorination with KF catalyzed by polymer-supported phosphonium salts under solid–solid–liquid phase transfer conditions

Fluorination of 2,4-dinitrochlorobenzene (DNCB) with solid KF was conducted in the presence of polymer-supported tetraphenylphosphonium chloride catalyst under solid–solid–liquid (S–S–L) phase transfer conditions. The triphase fluorination obeyed zero-order kinetics with respect to DNCB concentration and first-order kinetics with respect to the catalyst concentration. The apparent activation energy for the fluorination was estimated as about 40 kJ/mol. On the basis of these results, the ion exchange reaction between the Cl − ion of the supported catalyst and the F − ion of KF was concluded to be rate-determining in this S–S–L triphase fluorination. The addition effect of water on the triphase fluorination was discussed by means of both the prompted dissolution of solid KF and the decreased reactivity of the F − ion, induced by increased hydration.

Self-assembled ionophores as phase transfer catalysts

The nucleoside, 5′-( t-butyl-dimethylsilyl)-2′,3′-O-isopropylidene isoG 1, catalyzes the S N2 reactions of alkali and ammonium iodides with dodecyl mesylate 2 under both liquid-liquid and solid-liquid phase transfer conditions. IsoG 1 self-associates to give a complex that extracts the salts into CDCl 3 solution. Sodium iodide, in the presence of isoG 1, reacts faster with 2 than the other iodides under solid-liquid conditions. This reactivity difference is attributed to the open-faced structure of the ionophore-M + complex under solid-liquid conditions.

The Selective Reduction of Aldehydes Using Polyethylene Glycol-Sodium Borohydride Derivatives as Phase Transfer Reagents

A phase transfer reagent derived from PEG-sodium borohydride was developed which controlled both the activity and the amount of the reagent in the organic phase. Using this reagent under solid-liquid phase transfer conditions, it was found that aldehydes could be selectively reduced in the presence of ketones without concurrent reduction of the ketone group. The reactions were conducted at room temperature and were generally complete within two hours.

Studies on Glycosides XXI. Solid-Liquid Phase Transfer Catalyzed Reaction of Tetra-O-acetylglycopyranosyl Bromide with Active Methylene Compounds

2,3,4,6-Tetra-O-acetylglycopyranosyl bromide was reacted with active methylene compounds under solid-liquid phase-transfer catalyst conditions, involving anhydrous potassium phosphate as base and TBAB as catalyst in acetonitrile at room temperature, to give the corresponding tetra-O-acetylglycoside 2 in moderate yields.

A Direct Route to C-Vinylaziridines: Reaction of N-Sufonylimines with Allylic Ylides under Phase-Transfer Conditions or with Preformed Ylides at Low Temperature.

Allylic sulfonium salts 3, 5, 7, 11, 12, 13, and arsonium salt 14 react with aromatic, heteroaromatic, and alpha,beta-unsaturated N-sulfonylimines under solid-liquid phase-transfer conditions in the presence of KOH at room temperature to produce, respectively, vinyl-, (beta-phenylvinyl)-, and [beta-(trimethylsilyl)vinyl]aziridines in excellent yields within several minutes. In some cases, pyrroline compound 9 is obtained as a minor product. This aziridination reaction has also been carried out with preformed ylides, generated from sulfonium salts 3, 7, arsonium salt 14, and telluronium salts 15, 16 with a base in THF at -78 degrees C. In most examples, quantitative yields were achieved. However, the trans/cis selectivity of the reaction was not high in either case. A semistable allylic sulfonium ylide, i.e., dimethylsulfonium 3-(trimethylsilyl)allylide, was found to not undergo an expected [2,3]-sigma-rearrangement and so can also be used in this reaction.

Selective Mono- or Dialkoxylation of 2,4,6-Trichloro-1,3,5-triazine in Solid-Liquid Phase Transfer Conditions

Abstract In solid-liquid phase transfer conditions, both the primary and the secondary alcohols react cleanly with 2,4, 6-trichloro-1,3,5-triazine to give the corresponding mono or dialkoxy derivatives depending on the reagent molar ratio.

An efficient and highly stereoselective synthesis of trimethylsilylvinylcyclopropane derivatives via an organotelluronium salt: first example of catalytic Wittig-type cyclopropanation

A one-pot reaction of 3-trimethylsilylprop-2-enyl(diisobutyl)telluronium bromide 1 with α,β-unsaturated ketones gives, by way of Michael addition in the presence of caesium carbonate under solid–liquid phase-transfer conditions, trimethylsilylvinylcyclopropanes both in high to excellent yields and with high stereoselectivity. A similar high-yielding cyclopropanation occurs in THF/trace of water with diisobutyl telluride as catalyst in a one-pot reaction of (E)-3-bromo-1-trimethylsilylprop-1-ene with α,β-unsaturated ketones in the presence of caesium carbonate.