Trifluoromethyl Imines Research Articles

Regio- and Enantioselective Palladium-Catalyzed Asymmetric Allylation of N-Fluorenyl Trifluoromethyl Imine.

A palladium-catalyzed asymmetric allylation of N-fluorenyl trifluoromethyl imine with allylic acetates is disclosed. This method provides scalable and efficient access to polysubstituted chiral α-trifluoromethyl amines bearing two adjacent stereocenters and one allyl group in high yields with excellent regio-, diastereo-, and enantioselectivity. Importantly, this method also provides a powerful strategy for the synthesis of both regioisomeric products and the regioselectivity is controlled by the chiral catalysts and optically active substrates.

Direct Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Esters/Lactones via Umpolung Strategy.

Enabled by the discovery of new cinchonium salts and coadditives, a direct and efficient asymmetric access to trifluoromethylated γ-amino esters/lactones has been realized through the enantioselective and diastereoselective umpolung reaction of trifluoromethyl imines with acrylates or α,β-unsaturated lactones as carbon electrophiles. At 0.5-5.0 mol % catalyst loadings, the newly developed catalytic system activates a variety of imine substrates as unconventional nucleophiles to mediate highly chemo-, regio-, diastereo-, and enantioselective C-C bond forming reactions. The developed synthetic protocol represents an excellent strategy to target a series of versatile and enantiomerically enriched γ-amino esters/lactones in good to excellent yields from the readily available starting materials. Additionally, we found that the epi-vinyl catalysts based on cinchonidine and quinine promote a similarly high enantioselective reaction generating the opposite configuration of chiral products in a highly efficient manner, which allows convenient access to either the R- or S-enantiomer of the chiral amine products in high yields and excellent enantioselectivities.

Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives.

Novel cinchona alkaloid derived chiral phase-transfer catalysts enabled the highly chemo-, regio-, diastereo-, and enantioselective umpolung addition of trifluoromethyl imines to α,β-unsaturated N-acyl pyrroles. With a catalyst loading ranging from 0.2 to 5.0 mol %, this new catalytic asymmetric transformation provides facile and high-yielding access to highly enantiomerically enriched chiral trifluoromethylated γ-amino acids and γ-lactams.

Catalytic Asymmetric Synthesis of Trifluoromethylated γ‐Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives

AbstractNovel cinchona alkaloid derived chiral phase‐transfer catalysts enabled the highly chemo‐, regio‐, diastereo‐, and enantioselective umpolung addition of trifluoromethyl imines to α,β‐unsaturated N‐acyl pyrroles. With a catalyst loading ranging from 0.2 to 5.0 mol %, this new catalytic asymmetric transformation provides facile and high‐yielding access to highly enantiomerically enriched chiral trifluoromethylated γ‐amino acids and γ‐lactams.

Catalytic Asymmetric Synthesis of Chiral γ-Amino Ketones via Umpolung Reactions of Imines.

The first direct catalytic asymmetric synthesis of γ-amino ketones was realized by the development of a highly diastereoselective and enantioselective C-C bond-forming umpolung reaction of imines and enones under the catalysis of a new cinchona alkaloid-derived phase-transfer catalyst. In a loading ranging from 0.02 to 2.5 mol %, the catalyst activates a broad range of trifluoromethyl imines and aldimines as nucleophiles to engage in chemo-, regio-, diastereo- and enantioselective C-C bond-forming reactions with acyclic and cyclic enones, thereby converting these readily available prochiral starting materials into highly enantiomerically enriched chiral γ-amino ketones in synthetically useful yields. Enabled by this unprecedented umpolung reaction of imines, conceptually new and concise routes were developed for the asymmetric synthesis of nitrogen-heterocycles such as pyrrolidines and indolizidines.

Cinchonium Betaines as Efficient Catalysts for Asymmetric Proton Transfer Catalysis: The Development of a Practical Enantioselective Isomerization of Trifluoromethyl Imines.

We have developed a new class of cinchonium betaine catalysts bearing both a base moiety and an aromatic moiety as an N-substituent of the quinuclidine motif. These cinchonium betaines were found to promote proton transfer catalysis with 1000-5000 turnovers per 24 h, thereby enabling us to realize highly efficient enantioselective isomerization of trifluoromethyl imines to provide a practical access to optically active trifluoromethylated amines.

Asymmetric Synthesis of Trifluoromethylated Amines and Their Derivatives

Trifluoromethylated amines, especially optically active ones, are very important synthetic building blocks in the design of bioactive products. Over the past decades, the development of highly efficient methods for asymmetric synthesis of Trifluoromethylated amines and their derivatives has attracted a continuing interest. A brief overview will give an insight into the asymmetric synthesis of trifluoromethylated amines and their derivatives from trifluoromethyl imines, nucleophilic trifluoromethylation tamed, fluorine-containing allylic esters, and by enzymatic catalysis. Keywords: Trifluoromethylated amines, asymmetric synthesis, nucleophilic addition, hydrogenation.

Diastereoselective addition of some carbanions to an optically active trifluoromethyl imine derivative

Optically active trifluoromethyl 2-ethoxy-1-phenylethyl-1-imine can react with various carbanions diastereoselectively, and in hetero Diels–Alder addition and in Mannich reaction, it can be derived to the corresponding products with high optical purity.

ChemInform Abstract: Asymmetric Synthesis of Trifluoromethylated Amines via Catalytic Enantioselective Isomerization of Imines.

AbstractAn unprecedented, organocatalytic and highly enantioselective isomerization of trifluoromethyl imines is developed.

Asymmetric synthesis of trifluoromethylated amines via catalytic enantioselective isomerization of imines.

A new approach toward the asymmetric synthesis of optically active trifluoromethylated amines was enabled by an unprecedented, highly enantioselective catalytic isomerization of trifluoromethyl imines with a new chiral organic catalyst. Not only aryl but also alkyl trifluoromethylated amines could be obtained in high enantioselectivities.

ChemInform Abstract: Chiral Phosphoric Acid Catalyzed Transfer Hydrogenation: Facile Synthetic Access to Highly Optically Active Trifluoromethylated Amines.

AbstractThe desired products can be prepared from trifluoromethyl imines or trifluoromethyl ketones in the presence of organocatalyst BPA.

ChemInform Abstract: Synthesis of Optically Active Trifluoromethyl Substituted Diaziridines and Oxaziridines.

(E)-Trifluoromethyl imines were considered as ideal substrates to be transformed into the corresponding diaziridines by a direct amination reaction with nosyloxycarbamates. The diastereoselective induction was strongly controlled by the N-substituent. Similar results were obtained in the epoxidation reactions performed on the same substrates using m-CPBA as oxidant. Starting from enantiopure imines chiral diaziridines or oxaziridines were obtained with very high enantiopurity.

Synthesis of optically active trifluoromethyl substituted diaziridines and oxaziridines

( E)-Trifluoromethyl imines were considered as ideal substrates to be transformed into the corresponding diaziridines by a direct amination reaction with nosyloxycarbamates. The diastereoselective induction was strongly controlled by the N-substituent. Similar results were obtained in the epoxidation reactions performed on the same substrates using m-CPBA as oxidant. Starting from enantiopure imines chiral diaziridines or oxaziridines were obtained with very high enantiopurity.

ChemInform Abstract: Solvent‐Free Stereoselective Synthesis of (E)‐Trifluoromethyl Imines and Hydrazones.

AbstractA simple synthesis of the title compounds is achieved through uncatalyzed condensation of trifluoromethyl carbonyl compounds or their hemiacetals with primary amines.

Solvent-Free Stereoselective Synthesis of (E)-Trifluoromethyl Imines and Hydrazones

A new, green and efficient strategy for the synthesis of trifluoromethyl ketimines, aldimines, and hydrazones starting from the corresponding trifluoromethyl carbonyl compounds or their hemiacetals is reported. The condensation reactions were performed under solvent-free conditions with a range of amines or hydrazines and proceeded with high stereoselectivity, always giving only the E-isomer in very good yields.

The Chemistry of Trifluoromethyl Imines and Related Acetals Derived from Fluoral

AbstractFor Abstract see ChemInform Abstract in Full Text.

The chemistry of trifluoromethyl imines and related acetals derived from fluoral

Trifluoromethylated nitrogen-containing molecules have been shown to have important biological effects and their synthesis is in the focus of the pharmaceutical industry. In the last few years, simple nitrogen derivatives of fluoral, i.e. imines, acetals and oxazolidines, have emerged as powerful building blocks to synthesize these target molecules and relevant precursors. This review summarizes the chemistry of these "N-derivatives of fluoral", with special highlight on the syntheses of peptidomimetic units (amino alcohols, amino acids...) and heterocycles (piperidines, beta-lactams...).

BF3‐Promoted Aromatic Substitution of N‐Alkyl α‐Trifluoromethylated Imine: Facile Synthesis of 1‐Aryl‐2,2,2‐trifluoroethylamines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

BF3-Promoted Aromatic Substitution of N-Alkyl α-Trifluoromethylated Imine: Facile Synthesis of 1-Aryl-2,2,2-trifluoroethylamines

Abstract The aromatic substitution of three representative N-alkyl trifluoromethyl imines 1a–c (R: a, benzyl; b, benzhydryl; c, methyl), obtained from primary alkyl amines and trifluoroacetaldehyde ethyl hemiacetal, was used to investigate the preparation of 1-aryl-2,2,2-trifluoroethylamines. In the presence of BF3·OEt2, the reaction of imine 1 with various aromatic compounds proceeded smoothly at room temperature, giving N-alkyl-1-aryl-2,2,2-trifluoroethylamines in moderate-to-high yields. Moreover, successful regioselective removal of N-benzyl and N-benzhydryl groups was achieved by hydrolysis in hydrochloric acid or by palladium-catalyzed hydrogenolysis.

ChemInform Abstract: Extending the Scope of Ruppert′s Reagent: Trifluoromethylation of Imines.

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