Asymmetric Phase-Transfer Catalysis Research Articles

Light-mediated catalytic enantioselective difluoroalkylation of β-ketoesters via phase-transfer catalysis

Asymmetric phase-transfer catalysis has been used to control the moderately enantioselective addition of difluoroalkyl radicals to the enolates of β-ketoesters.

New Trends in Asymmetric Phase Transfer Catalysis

AbstractPhase Transfer Catalysis (PTC) is a powerful tool to perform reactions in a practical fashion, both in laboratory and industrial scale. Significant cost savings and major process improvements can be achieved in reactions performed under PTC conditions. In the last few years remarkable results in stereoselective reactions were achieved using chiral, non‐racemic quaternary ammonium salts. Moreover, the use of bulky, chiral phosphate anions paired with achiral cations to generate lipophilic ion pairs allowed to design new avenues for the stereoselective construction of important building blocks. Hydrogen bond interactions were also shown to provide new pathways for asymmetric nucleophilic substitutions using insoluble reagents under PTC conditions. This Review will focus on recent advances in developing practical synthetic routes to construct molecules in a stereoselective fashion under PTC conditions.

Copper(I)-catalyzed asymmetric alkylation of α-imino-esters

Asymmetric alkylation of enolates is one of the most direct and important reactions to prepare α-chiral carbonyl compounds. Except for the classical methods that rely on the use of chiral auxiliaries, asymmetric catalysis emerged as a powerful tool, especially asymmetric phase-transfer catalysis. However, in the field of transition metal catalysis, only limited success with asymmetric alkylation of enolates was achieved. Hereby, we disclose a copper(I)-catalyzed asymmetric alkylation of α-imino-esters with various alkyl halides, including allyl bromides, propargyl bromide, benzyl bromides, α-bromo carbonyl compounds, and alkyl iodides. Both linear and cyclic α-imino-esters serve as competent pronucleophiles in the alkylation, which affords α-amino acid derivatives bearing either a trisubstituted or a tetrasubstituted stereogenic carbon center in high to excellent enantioselectivity. Control experiments indicate that the α-imino-ester is activated by a chiral copper(I)-phosphine complex through coordination, thus enabling facile deprotonation to provide a stabilized copper(I)-enolate in the presence of a mild base. Finally, the mildly basic nature allows the asymmetric alkylation of chiral dipeptides with excellent both chemo- and enantioselectivities.

Synthesis of cyclic amino acid baikiain via asymmetric phase transfer catalysis

AbstractThe synthesis of the cyclic, naturally occurring amino acid baikiain from glycine and cis‐1,4‐butenediol is reported. The key step of the synthesis is an enantioselective phase transfer catalyzed allylation of the benzophenone imine of glycine t‐butyl ester, catalyzed by a cinchonidine quaternary ammonium salt, which provided the allylated glycine in 82% yield and 80% e.e. Further deprotection and hydrolysis of the Schiff base followed by an intramolecular Mitsunobu ring closure reaction yielded the corresponding piperidine ring system in 77% yield, which by hydrolysis yielded baikiain hydrochloride in 36% overall yield. Hydrogenation of the double bond could provide access to (S)‐pipecolic acid, which is also an important chiral synthon.

Recent Asymmetric Phase-Transfer Catalysis with Chiral Binaphthyl-Modified and Related Phase-Transfer Catalysts over the Last 10 Years.

In this personal account, we describe our recent advances in the three types of phase-transfer catalysis for various transformations including asymmetric induction: Firstly, asymmetric phase-transfer catalysis with Maruoka-type C2 -symmetric chiral biaryl-modified tetraalkylammonium salts and phosphonium salts; Secondly, asymmetric phase-transfer catalysis under base-free and neutral conditions; Thirdly, hydrogen-bonding catalysis using tetraalkylammonium and trialkylsulfonium salts. These three different strategies are illustrated by using various phase-transfer catalyzed transformations.

Design of Maruoka catalysts for asymmetric Phase-Transfer catalysis

Design of Maruoka catalysts for asymmetric Phase-Transfer catalysis

Enantioselective halogenation via asymmetric phase‐transfer catalysis

AbstractThe asymmetric phase‐transfer catalysis (PTC) is a flourishing field of contemporary synthetic organic chemistry, and this prominent methodology has been tremendously successful in enantioselective halogenations. Both electrophilic and nucleophilic reaction manifolds were enabled through the exploitation of highly ordered ion pairing and/or hydrogen‐bonding interactions around a carefully designed chiral phase‐transfer catalyst with an insoluble halogenating reagent as well as a suitable substrate. Fluorination has been the most fruitful, and encouraging results have also been documented with heavier halogens. This review surveys examples of various enantioselective halogenations via the asymmetric PTC from its beginning to prosperity over the past decade.

Atropselective synthesis of N-aryl pyridones via dynamic kinetic resolution enabled by non-covalent interactions.

The dynamic kinetic resolution of C-N atropisomeric pyridones was achieved via asymmetric phase-transfer catalysis, exploiting a rotational barrier-lowering hydrogen bond in the starting materials. X-ray and NMR experiments revealed the presence of a barrier-raising ground state CH⋯π interaction in the product, supported by DFT calculations. A co-crystal of the quinidine-derived phase-transfer catalyst and substrate reveals key substrate-catalyst non-covalent interactions.

Asymmetric epoxidation of enones: effect of surfactants, radical scavengers and morphology of catalysts on reaction rates, chemical yields and enantioselectivities in phase-transfer catalysis

Highly enantioselective epoxidation of enones has been accomplished with asymmetric phase-transfer catalysis using Cinchona alkaloid-derived meta-dimer catalysts.

Phase-transfer catalysis and the ion pair concept

AbstractThis review outlines the recent advances in the field of asymmetric phase-transfer catalysis and the ion-pair concept including alkylation of amino acids and peptides, oxyindoles and other substrates, conjugate additions, fluorinations, photo-induced phase-transfer catalysis, Nitro-Mannich reactions, heterocyclizations and cycloadditions for the preparation of heterocycles, derivatization of isoxazoles, umpolung conjugate addition of imines and other three asymmetric reactions.

Chiral Phase-Transfer Catalysts with Hydrogen Bond: A Powerful Tool in the Asymmetric Synthesis

Asymmetric phase-transfer catalysis has been widely applied into organic synthesis for efficiently creating chiral functional molecules. In the past decades, chiral phase-transfer catalysts with proton donating groups are emerging as an extremely significant strategy in the design of novel catalysts, and a large number of enantioselective reactions have been developed. In particular, the proton donating groups including phenol, amide, and (thio)-urea exhibited unique properties for cooperating with the phase-transfer catalysts, and great advances on this field have been made in the past few years. This review summarizes the seminal works on the design, synthesis, and applications of chiral phase-transfer catalysts with strong hydrogen bonding interactions.

Enantioselective Mannich reaction of γ-malonate-substituted α,β-unsaturated esters with N-Boc imines catalyzed by chiral bifunctional thiourea-phosphonium salts

A novel enantioselective Mannich reaction of γ-malonate-substituted α, β-unsaturated esters with N-protected arylaldimines was realized by using asymmetric phase-transfer catalysis (APTC). With amino acid-derived bifunctional thiourea-phosphonium salts as a catalyst, a series of enantio-enriched Mannich products could be synthesized under very mild and simple reaction conditions with high yields and enantioselectivities.

NL2+ Systems as New-Generation Phase-Transfer Catalysts

Phase-transfer catalysts (PTCs), currently, are one of the most important tools of chemists for performing organic reactions. PTCs accelerate several types of reactions in biphasic systems, giving excellent yields of the desired product. Most of the PTCs belong to the general formula NR4+X-. In the recent past, several compounds possessing a novel scaffold with the general formula NL2+X- have been reported as PTCs. In the NL2+ species, a nitrogen atom with a formal positive charge accepts electron density from electron-donating ligands. Electronic structure studies reported in the literature confirmed the possibility of L → N coordination (donor-acceptor) interactions in these species, and thus, this class of compounds are known as divalent NI compounds. These species are reported to exhibit better catalytic potential in comparison to the traditional NR4+ systems. Some of the NL2+ systems are found to be useful in asymmetric phase-transfer catalysis. Thus, these systems offer extensive opportunities for exploring the catalytic properties and novel mechanistic aspects associated with their unique electronic structure. In this paper, the synthesis, electronic, and structural properties and the applications in catalysis of the NL2+-based PTCs are reviewed with their bright future scope in catalytic organic chemistry.

Enantioselective Alkylation of N-Arylhydrazones Derived from α-Keto Esters and Isatin Derivatives through Asymmetric Phase-Transfer Catalysis.

The phase-transfer-catalyzed asymmetric alkylation reactions of N-arylhydrazones derived from α-keto-esters and isatin derivatives afford enantioenriched azo compounds that bear a tetra-substituted carbon stereocenter in good yields with high chemo- and enantioselectivity. The alkylation products can be readily converted into chiral amino esters, hydrazine derivatives, and aza-β-lactams without loss of enantiopurity.

ChemInform Abstract: A New Generation of Chiral Phase‐Transfer Catalysts

AbstractReview: 44 refs.

ChemInform Abstract: Contemporary Asymmetric Phase Transfer Catalysis: Large‐Scale Industrial Applications

AbstractReview: [70 refs.

Contemporary Asymmetric Phase Transfer Catalysis: Large-Scale Industrial Applications

Asymmetric phase transfer catalysis has been recognized as an approach that is greener and more sustainable than synthetic alternatives and has evolved into one of the most practical methods in challenging enantioselective synthesis. An overview of the current status of asymmetric phase transfer catalysis in industry is presented by summarizing research progress from both journal publications and patent applications.

Enantioselective Synthesis of Dialkylated α-Hydroxy Carboxylic Acids through Asymmetric Phase-Transfer Catalysis.

In the presence of an L-tert-leucine-derived urea-ammonium salt as phase-transfer catalyst, a highly enantioselective alkylation of 5H-oxazol-4-ones with various benzyl bromides and allylic bromides has been developed to furnish catalytic asymmetric synthesis of biologically important dialkylated α-hydroxy carboxylic acids with a broad scope. This is the first example of an L-amino acid-derived urea-ammonium salt being used as a phase-transfer catalyst with excellent catalytic efficiency.

Asymmetric Phase-Transfer Catalysis with Homo- and Heterochiral Quaternary Ammonium Salts: A Theoretical Study

A thorough theoretical study of phase-transfer quaternary ammonium catalysts designed by the Maruoka group has been performed in an attempt to gain better understanding of the properties and catalytic behavior of the homo- and heterochiral forms of these systems. The conformationally flexible analogue is found to easily undergo interconversion from the homo- to the heterochiral form driven by the higher thermodynamic stability of the heterochiral isomer and resulting in alternation in catalytic behavior. Theoretical calculations of (1)H NMR spectra of the two isomers for different model systems are in good agreement with the experimental data, allowing us to conclude that the upfield shift of signals for the benzylic protons in the heterochiral form could be explained by an increase in the shielding effect of the aromatic parts of the system around these protons due to the conformational changes. By applying the automated transition state (TS) search procedure for the alkylation of glycine derivatives catalyzed by the homo-/heterochiral form of a conformationally rigid analogue, we were able to locate more than 40 configurations of the TS structures. In brief, the homochiral form was theoretically confirmed to catalyze the formation of the predominant R-product, while for the heterochiral form the catalytic activity is found to depend on two factors: (i) formation of a tight ion pair between the catalyst and the glycine derivative, which results in a decrease in the reaction rate, in agreement with the experimental data, and formation of only the R-product, and (ii) the possibility that the reaction occurs without the initial formation of the ion pair or after its dissociation, in which case the formation of an S-product is predominant. The combined effects of both factors would explain the lower reaction rate and the poor enantioselectivity observed experimentally for the heterochiral form.

Enantioselective Addition of Thiols to Imines Catalyzed by Thiourea–Quaternary Ammonium Salts

Asymmetric phase-transfer catalysis was first applied to the synthesis of chiral N,S-acetals by using amino acid-based bifunctional thiourea-ammonium salt catalysts. The reaction could be performed on the gram scale to give up to 93% ee and 99% yield with