Asymmetric Organocatalysis Under Mechanochemical Conditions.

Asymmetric organocatalysis is a robust methodology providing access to numerous valuable compounds while having green chemistry principles in mind. The realization of organocatalytic transformation under solvent-free mechanochemical conditions brings additional benefits in terms of yields, selectivities, and, last but not least overall improved sustainability. This overview describes developments in the use of mechanochemistry as a vehicle for asymmetric organocatalytic transformations.

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates.

Herein, we present the synthesis and utilization of derivatives of 4-benzo[][1,4]thiazine-3-carboxylic acid. These benzothiazine compounds were assembled via the coupling of aminothiols and bromopyruvates. Oxidative dimerization of these starting materials was also observed and the corresponding benzothiazine dimers were isolated.

Organocatalytic Diastereodivergent Enantioselective Formal oxa-Diels-Alder Reaction of Unsaturated Ketones with Enoates Under Liquid-Assisted Grinding Conditions.

Chiral heterocycles occur in many compounds of interest, but their efficient synthesis is challenging. This study concerns the enantioselective and diastereoselective synthesis of densely substituted chiral pyran derivatives. Diastereodivergence of the oxa-Diels-Alder reaction is achieved by using either a bifunctional amino-thiourea or a monofunctional quinine organocatalyst under ball-milling conditions.

-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts.

The synthesis of bifunctional -sulfinylureas and thioureas with an appended pyrrolidine unit is presented. These organocatalysts were evaluated in Michael additions of aldehydes to nitroalkenes both under solvent-free conditions and in solution. The -sulfinylurea catalyst was more efficient than the corresponding thiourea.

Green Asymmetric Organocatalysis.

Asymmetric organocatalysis is becoming one of the main tools for the synthesis of chiral compounds that are needed as medicines, crop protection agents, and other bioactive molecules. It can be effectively combined with various green chemistry methodologies. Intensification techniques, such as ball milling, flow, high pressure, or light, bring not only higher yields, faster reactions, and easier product isolation, but also new reactivities.

Why do thioureas and squaramides slow down the Ireland-Claisen rearrangement?

A range of chiral hydrogen-bond-donating organocatalysts was tested in the Ireland-Claisen rearrangement of silyl ketene acetals. None of these organocatalysts was able to impart any enantioselectivity on the rearrangements. Furthermore, these organocatalysts slowed down the Ireland-Claisen rearrangement in comparison to an uncatalyzed reaction.

Bifunctional Amine-Squaramides as Organocatalysts in Michael/Hemiketalization Reactions of β,γ-Unsaturated α-Ketoesters and α,β-Unsaturated Ketones with 4-Hydroxycoumarins.

The catalytic efficiency of various amine-squaramides was tested in Michael/hemiketalization reactions of 4-hydroxycoumarines with two types of enones. Tertiary amine-squaramide organocatalysts afforded the best results regarding both activity and enantioselectivity when β,γ-unsaturated α-ketoesters were used as the Michael acceptors (yields up to 98%, enantioselectivities up to 90% ee). On the other hand, the primary amine-squaramides are the best choice for related reactions of 4-hydroxycoumarins with enones.

Asymmetric organocatalytic SOMO reactions of enol silanes and silyl ketene (thio)acetals.

Organocatalytic SOMO reactions can provide access to various α-functionalized carbonyl compounds. Chiral imidazolidinones catalysed the organo-SOMO reactions of aldehydes and ketones with cyclic and acyclic enol silanes. The resulting chiral dicarbonyl compounds were obtained in yields of up to 80% and enantiomeric purities of up to 90% ee.

Ferrocene phosphane-heteroatom/carbon bidentate ligands in asymmetric catalysis.

Chiral ferrocene derivatives belong to privileged ligand classes for asymmetric transition metal catalysed reactions. Hetero-bidentate phosphane ligands are hybrid ligands, which combine the properties of phosphorus with those of other donor atoms. This feature creates further asymmetry around the metal centre, which may be helpful for increasing the stereoinduction.

Michael additions of methylene active compounds to chalcone in ionic liquids without any catalyst: the peculiar properties of ionic liquids.

Michael additions of malonodinitrile as well as several other reagents to chalcone have been found to proceed well in pure ionic liquids, without the addition of any catalyst. The catalytic effect of the residual acidity caused by hydrolysis of ionic liquids anions was excluded because HCl in dichloromethane did not catalyse the Michael addition of malonodinitrile. Piperidine was tested as the catalyst and was found to be a much better catalyst in ionic liquids than in dichloromethane.

Michael addition of thiols to alpha-enones in ionic liquids with and without organocatalysts.

Seventeen organocatalyts were tested for their ability to catalyst the addition of thiophenols to chalcones in [bmim]PF6. The products were isolated in high yield after a short reaction time, but no stereoselectivity was observed. The reactions also proceeded (without any stereoselectivity) in four other ionic liquids.

The sonochemical arylation of active methylene compounds.

The sonochemical arylation of active methylene compounds with haloarenes have been studied. The reaction course was found to be dependent on the electron-withdrawing properties of substituent and the leaving group of haloarenes as well as of the character of active methylene compounds. The results of the sonochemical experiments were just slightly better than in the classical ones's, exception being reactions with phenylsulfonylacetonitrile.

Ultrasound effect on the aromatic nucleophilic substitution reactions on some haloarenes.

The sonochemical nucleophilic aromatic substitutions on haloarenes with different amines have been studied. A beneficial ultrasound effect was observed and high yields of the products were obtained after 15-30 min sonication. The reaction course of the nucleophilic aromatic substitution was found to be strongly dependent on nucleophilicity, bulkiness, and boiling point of amines as well as on the electron-withdrawing property of the substituents on the haloarenes.