Dominique Cahard

Asymmetric Construction of Stereogenic Carbon Centers Featuring a Trifluoromethyl Group from Prochiral Trifluoromethylated Substrates

Department of Chemistry, Tianjin University, Tianjin 300072, China; Department of Applied Chemistry, China Agricultural University, Beijing 100193, China; UMR 6014 CNRS, Laboratoire COBRA de l’IRCOF, Université et INSA de Rouen, Rue Tesniere, F-76130 Mont Saint Aignan, France; and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China

Ionic liquids and chirality: opportunities and challenges

This review deals with recent advances in the investigation of ionic liquids (ILs) in the field of chirality, i.e. asymmetric synthesis and new chiral solvents.

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

Summary Since the discovery by Yagupolskii and co-workers that S-trifluoromethyl diarylsulfonium salts are effective for the trifluoromethylation of thiophenolates, the design and synthesis of electrophilic trifluoromethylating reagents have been extensively researched in both academia and industry, due to the significant unique features that trifluoromethylated compounds have in pharmaceuticals, agricultural chemicals, and functional materials. Several effective reagents have been developed by the groups of Yagupolskii, Umemoto, Shreeve, Adachi, Magnier, Togni and Shibata. Due to the high stability and reactivity of these reagents, a series of Umemoto reagents, Togni reagent and Shibata reagent are now commercially available. In this review, we wish to briefly provide a historical perspective of the development of so-called “shelf-stable electrophilic trifluoromethylating reagents”, although this field is in constant development.

Chiral dipeptide mimics possessing a fluoroolefin moiety: a relevant tool for conformational and medicinal studies

The replacement of the amide bond in a peptide backbone is a promising strategy in peptidomimetic drug research. Over the various amide bond surrogates, the fluoroolefin moiety has been successfully developed as an effective mimic. Today, fluorine-containing compounds account for a large proportion of new active molecules in life sciences. The synthesis of fluoroolefin peptide mimics is not a trivial task and innovative approaches often need to be addressed, in particular for the stereocontrol of the double bond configuration and the chiral centres adjacent to the fluoroalkene. These fluorinated peptidomimetics have been synthesised and evaluated as metabolically stable and/or conformationally constrained analogs of enzyme inhibitors, and as tools for probing the function, structure, and binding process of receptors.

Enantioselective Base‐Free Electrophilic Amination of Benzofuran‐2(3H)‐ones: Catalysis by Binol‐Derived P‐Spiro Quaternary Phosphonium Salts

However, enantioselective synthesis of such significant chiral benzofuran-2(3H)-ones remains a considerable challenge. Catalytic enantioselective introduction of substituents at the C3 position represents the most direct approach to chiral benzofuranones. For instance, Vedejs et al. and Hill and Fu have presented the asymmetric Black rearrangement of Oacylated benzofuranones by means of chiral derivatives of 4dimethylaminopyridine (DMAP) to afford enantioenriched C-acylated isomers with up to 98 % enantiomeric excess. Very recently, two other groups reported the enantioselective conjugate addition reactions of benzofuran-2(3H)-ones to a,b-unsaturated carbonyl compounds, in which chiral thioureas and amines were used as catalysts. Enantioselective introduction of a heteroatom group at the C3 position would substantially broaden the benzofuranone chemistry and offer more functionalized chiral products. Herein, we present a hitherto unknown catalytic enantioselective amination of benzofuranones by employing a new class of rigid chiral Pspiro quaternary phosphonium salts as organocatalysts. Over the past decades, organocatalysis that exploits the use of chiral quaternary ammonium salts has emerged as an area of intense interest in asymmetric synthesis owing to its operational simplicity and mild reaction conditions. 8] A number of quaternary ammonium salt catalysts have demonstrated useful levels of enantioselectivity in a wide range of asymmetric reactions. Furthermore, a recent breakthrough in this field involved the design and application of chiral quaternary phosphonium salts in catalytic asymmetric synthesis. For examples, the group of Ooi developed a series of P-spiro tetraaminophosphonium salts as chiral Brønsted acids for substrate recognition and functional-group activation through hydrogen bonding. Maruoka and co-workers reported other chiral quaternary tetraalkylphosphonium salts and their use in asymmetric phase-transfer catalysis. Despite the above mentioned progress, this field is still in its infancy and the construction of new phosphonium catalysts is still in great demand to meet the need of many challenging asymmetric reactions. Since 1,1’-binaphthyl-based enantiopure chiral materials are among the most readily available privileged sources of chirality, chemical modification of binaphthyls resulting in the formation of new modular structures for catalytic application has been a proven strategy for the development of novel chiral catalysts. We envisioned that the introduction of two chiral 2,2’-bis(methylene)-1,1’-binaphthyl moieties onto a phosphorus center would form a rigid P-spiro tetraalkylphosphonium framework, thus enabling a high level of asymmetric induction. A series of novel homochiral tetraalkylphosphonium bromides 1 possessing a [7.7] spirocyclic core were readily prepared by the reaction of (S)-4,5-dihydro-3Hdinaphtho[2,1-c :1’,2’-e]phosphepine with (S)-3,3’-disubstituted 2,2’-bis(bromomethyl)-1,1’-binaphthyls and purified in analytically pure form after one simple recrystallization. Crystals suitable for X-ray diffraction analysis were obtained for the quaternary phosphonium salt 1a. The ORTEP view of this structure is shown in Figure 2. As expected, the two binaphthylmethylene units are twisted at the phosphorus center. The dihedral angle between the planes of the two naphthyl units is 69.18. It was expected that the conformational rigidity imposed by the P-spiro scaffold could potenFigure 1. Examples of chiral benzofuran-2(3H)-ones.

Electrophilic Fluorination Mediated by Cinchona Alkaloids: Highly Enantioselective Synthesis of α‐Fluoro‐α‐phenylglycine Derivatives

A decisive step forward: A one-step fluorination on modified cinchona alkaloids produced a new range of enantiopure fluorinating agents that display high enantioselectivities in electrophilic fluorination. The first enantioselective synthesis of N-protected α-fluorophenylglycine derivatives was achieved with an enantiomeric excess up to 94 % [Eq. (a); R=Et, CN; HMDS=hexamethyldisilazanide].

Palladium(II)-Catalyzed Directed Trifluoromethylthiolation of Unactivated C(sp3)–H Bonds

The synthesis of trifluoromethylthiolated aliphatic acid derivatives by Pd-catalyzed C(sp(3))-H bond functionalization was developed. Using a bidentate directing group, the direct and selective introduction of a SCF3 moiety was possible on a range of amides with remarkable selectivity for C(sp(3))-centers with an electrophilic SCF3 source and pivalic acid as an additive. This work constitutes an example of the unactivated C(sp(3))-SCF3 bond formation by C-H activation offering a new access to relevant molecules.

New polymer-supported chiral phase-transfer catalysts in the asymmetric synthesis of α-amino acids: the role of a spacer

Abstract Polymer-supported cinchona alkaloid salts with different spacers were used as phase-transfer catalysts in the asymmetric C -alkylation of N -diphenyl methylene glycine tert -butyl ester. Various catalysts and alkylation conditions were studied, the best result being 81% e.e. with cinchoninium iodide bound to polystyrene with a four-carbon spacer.

Ruthenium‐Catalyzed Redox Isomerization of Trifluoromethylated Allylic Alcohols: Mechanistic Evidence for an Enantiospecific Pathway

Transfer news: A synthetic approach to chiral β-CF(3)-substituted saturated carbonyl compounds has been developed in which ruthenium complexes efficiently catalyze the redox isomerization of CF(3)-bearing allylic alcohols by an intramolecular suprafacial enantiospecific 1,3-hydrogen transfer (see scheme). This method was used for the enantioselective synthesis of (S)-CF(3)-citronellol.

Poly(ethylene glycol) supported cinchona alkaloids as phase transfer catalysts: application to the enantioselective synthesis of α-amino acids

We have demonstrated that quaternary ammonium salts of cinchona alkaloids grafted to a poly(ethylene glycol) matrix are efficient homogeneous catalysts in the enantioselective alkylation of glycine Schiff base derivatives. The role of the solvent, the molecular weight of the polymer and the anchorage site on the alkaloid were investigated, leading to ees up to 81%.