Julien Legros

Solvent-Promoted and -Controlled Aza-Michael Reaction with Aromatic Amines

1,4-Addition of anilines onto Michael acceptors proceeds easily in specific polar protic solvents, without any promoting agent. According to the solvent and to the electrophile, the selectivity of the reaction can be finely tuned. With methyl acrylate as electrophile, only monoaddition takes place in water, while the diadduct is yielded in hexafluoroisopropyl alcohol (HFIP). The use of methyl vinyl ketone as a partner affords the monoadduct in water, the diadduct in trifluoroethanol (TFE), and the quinoline in HFIP.

Influence of the structure of polyfluorinated alcohols on Brønsted acidity/hydrogen-bond donor ability and consequences on the promoter effect.

The influence of substituents on the properties of tri- and hexafluorinated alcohols derived from 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) was examined. Measurements of specific solvent-solute interactions revealed that H-bond donation (HBD) of fluorinated alcohols is sensitive to the steric hindrance of the OH group, whereas their Brønsted acidity is dependent only on the number of fluorine atoms. For hexafluorinated alcohols (HFAs), their association with amines characterized by X-ray diffraction showed that the balance between HBD and acidity is influenced by their structure. Moreover, the ability of HFAs to donate H-bonds is exerted in synclinal (sc), synperiplanar (sp), and also antiperiplanar (ap) conformations along the C-O bond. Comparison of the effects of fluorinated alcohols as promoting solvents in three reactions is reported. The positive correlation between rate constants and H-bonding donation ability for sulfide oxidation and imino Diels-Alder reaction brings to light the role of this property, while acidity might have a minor influence. In the third reaction, epoxide opening by piperidine, none of these properties can clearly be put forward at this stage.

Synthesis of pyrazoles through catalyst-free cycloaddition of diazo compounds to alkynes

The synthesis of pyrazoles via1,3-dipolar cycloaddition of diazo compounds to alkynes proceeds easily by heating. With α-diazocarbonyl substrates the reactions are conducted under solvent-free conditions affording the pyrazole products in high yields without any work up or purification.

Urea-Hydrogen Peroxide/Hexafluoro-2-propanol: An Efficient System for a Catalytic Epoxidation Reaction without a Metal

Hexafluoro-2-propanol (HFIP) exhibits a unique ability to release and activate H2O2 from the urea-hydrogen peroxide adduct (UHP). This UHP/HFIP system was investigated in epoxidation of olefins, using various fluoroketones as catalysts. With reactive olefins, no catalyst was required. With monosubstituted olefins, epoxides were obtained in high yields by using catalytic amounts (3−5%) of perfluorodecan-2-one. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Fluorous 4‐N,N‐Dimethylaminopyridine (DMAP) Salts as Simple Recyclable Acylation Catalysts

The recyclability of organicand metal-based catalysts is of prime interest for the development of sustainable synthesis processes. Since the pioneering work of the groups of Litvinenko and Steglich, who independently reported organocatalyzed acylation reactions with 4-N,N-dimethylaminopyridine (DMAP), dialkylaminopyridines still remain in the limelight. Thus, remarkable developments are regularly reported, as exemplified by the emergence of more potent analogues, even chiral, as catalysts for a diverse range of reactions. Unfortunately, these powerful organocatalysts exhibit acute dermal toxicity, whereas the corresponding salts only produce local irritation by skin contact. To avoid dissemination of these harmful chemicals in the environment, recyclable 4-aminopyridines have been prepared through immobilization on organic or inorganic supports. Although some remarkable systems emerged, those exhibiting significant activity coupled with complete recyclability are scarce. In 2007, Gun ko, Connon, and coworkers reported a very elegant magnetic-nanoparticle-supported DMAP that can be used several times without loss in activity and that is simply recovered by using an external magnet. 12] However, a limit in the molecular weight of the support is highly desirable to avoid the use of a quantity of immobilized catalyst larger than that of the substrate. Alternatively, fluorous techniques also offer a very attractive way to selectively recover a compound tagged with perfluorinated chains from a complex reaction mixture. Although this strategy originally involved fluorous solvents or silica, the current trend tends toward simple solubility modulation of fluorous catalysts in conventional media, for recovery through precipitation. In the field of catalysis, the fluorous approach has been widely applied to metal catalysts by means of fluorinated ligands. In contrast, reports on fluorous organocatalysis are still scarce, 19] and the field is only at an early stage of development. In this context, we recently reported the preparation of an efficient fluorous aminopyridine for esterification of hindered alcohols, which suffered from poor recyclability. We now report the use of an easily accessible fluorous salt of DMAP, 1-Rf, as an active and recyclable acylation catalyst, under simple conditions.

A database of dispersion-induction DI, electrostatic ES, and hydrogen bonding α1 and β1 solvent parameters and some applications to the multiparameter correlation analysis of solvent effects.

For about 300 solvents, we propose a database of new solvent parameters describing empirically solute/solvent interactions: DI for dispersion and induction, ES for electrostatic interactions between permanent multipoles, α1 for solute Lewis base/solvent Lewis acid interactions, and β1 for solute hydrogen-bond donor/solvent hydrogen-bond acceptor interactions. The main advantage over previous parametrizations is the easiness of extension of this database to newly designed solvents, since only three probes, the betaine dye 30, 4-fluorophenol, and 4-fluoroanisole are required. These parameters can be entered into the linear solvation energy relationship A = A0 + di(DI) + eES + aα1 + bβ1 to predict a large number of varied physicochemical properties A and to rationalize the multiple intermolecular forces at the origin of solvent effects through a simple examination of the sign and magnitude of regression coefficients di, e, a, and b. Such a rationalization is illustrated for conformational and tautomeric equilibria and is supported by quantum-mechanical calculations.

An efficient and robust fluoroketone catalyst epoxidation

The fluoroalkylketone 2 is an efficient catalyst in the epoxidation reaction using Oxone® as oxidant. In hexafluoro-2-isopropanol (HFIP), the ketone can be used in a catalytic amount (1 or 5 mol%) with only 1.5 equiv. of Oxone®. The reaction gave good yields of epoxides for a number of olefin substrates, included low reactive ones.

Benefits of a Dual Chemical and Physical Activation: Direct aza-Michael Addition of Anilines Promoted by Solvent Effect under High Pressure.

The unique combination of hexafluoroisopropanol (HFIP) employed as solvent and hyperbaric conditions (10-15 kbar) allows unprecedented 1,4-addition of poor nucleophiles, such as aromatic amines, onto sluggish (cumbersome) Michael acceptors without any promoter or workup.

Selective monomethylation of primary amines with simple electrophiles

Direct monomethylation of primary amines with methyl triflate was achieved with high selectivity (up to 96%). The key point of this single methyl transfer stems from the use of HFIP as the solvent that interferes with amines and avoids overmethylation.

Trifluoromethylcyclohexane as a new solvent? Limits of use

Abstract Reactivity and stability of trifluoromethylcyclohexane (TFMC) has been investigated towards various reagents, in order to evaluate its possible use as solvent. TFMC is stable in most oxidizing conditions, indicating the protective effect of a fluoroalkyl substituent towards oxidation, and surprisingly, it is also very stable towards strong bases. TFMC has also been assessed as a chlorinated solvent substitute in some reactions. It is clearly adapted as a CCl 4 substitute in allylic bromination reaction.