Radovan Šebesta

Catalysts with ionic tag and their use in ionic liquids

The concept of homogeneous supported catalysts has emerged as a useful alternative to homogeneous as well as heterogeneous catalysis, possibly combining positive aspects of both. Designing catalysts with respect to not only their catalytic activity but also their physical-chemical properties, appears to be a possible way towards sustainable chemical synthesis. Such tailored catalytic systems would ideally have high catalytic activities and some property enabling their efficient recycling. We reviewed the field of specifically designed ionic catalysts used mostly in ionic liquids.

Organocatalyst Efficiency in the Michael Additions of Aldehydes to Nitroalkenes in Water and in a Ball‐Mill

The enantioselective organocatalytic Michael addition in aqueous solution was compared with the reaction performed under solvent‐free ball‐milling conditions. A range of pyrrolidine‐derived organocatalysts were tested in the addition of aldehydes to nitroalkenes. Both procedures afforded good yields, diastereoselectivities, and enantioselectivities. The best catalyst in aqueous media was O‐lauroyl‐trans‐4‐hydroxyproline, whilst the ball‐milling technique was most‐efficient with α,α‐diphenyl‐2‐pyrrolidinemethanol trimethylsilyl ether.

Enantioselective One-Pot Conjugate Addition of Grignard Reagents to Cyclic Enones Followed by Amidomethylation

Enantioselective conjugate addition of Grignard reagents to enones, catalyzed by Cu-Taniaphos or Josiphos complex, affords chiral enolates. Ensuing one-pot Mannich reaction with TiCl(4)-generated imine leads to aminocarbonyl compounds with benzyloxycarbonyl-protected nitrogen. Both diastereomers of these compounds are isolated in moderate yields but high enantiomeric purities (up to er 97.5:2.5).

Enantioselective organocatalysis using SOMO activation

Enamines, formed from the corresponding carbonyl compounds and appropriate chiral amine catalysts, can be oxidized to radical cation species. These radical cations can be intercepted by a range of SOMO-philic reagents, such as alkenes, arenes and some heteroatom based reagents. This methodology affords diversely substituted chiral carbonyl compounds. Organo-SOMO activation expanded the scope of enamine/iminium based organocatalytic transformations and it enables new reaction partners to be combined efficiently.

Experimental and Theoretical Studies in Hydrogen-Bonding Organocatalysis

Chiral thioureas and squaramides are among the most prominent hydrogen-bond bifunctional organocatalysts now extensively used for various transformations, including aldol, Michael, Mannich and Diels-Alder reactions. More importantly, the experimental and computational study of the mode of activation has begun to attract considerable attention. Various experimental, spectroscopic and calculation methods are now frequently used, often as an integrated approach, to establish the reaction mechanism, the mode of activation or explain the stereochemical outcome of the reaction. This article comprises several case studies, sorted according to the method used in their study. The aim of this review is to give the investigators an overview of the methods currently utilized for mechanistic investigations in hydrogen-bonding organocatalysis.

Enantioselective Cu-Catalyzed Functionalizations of Unactivated Alkenes

Copper hydride or copper boranyl species have already been used in reactions with Michael acceptors. Recently, notable advances have been described and the methodology extended to unactivated alkenes as well. In situ generated copper hydride ligated with chiral ligands is able to catalyze enantioselective aminations of alkenes. Furthermore, transient organocopper species formed upon initial hydrocupration of the alkene can be intercepted by other electrophiles such as imines, organohalides, or boranes.

Enantioselective addition of oxazolones to N-protected imines catalysed by chiral thioureas

Hydrogen bond-catalysed aza-Mannich addition of oxazolones to various protected aldimines has been developed. The resulting, highly functionalized, oxazolones contain a quaternary stereogenic centre and can serve as precursors for chiral α,β-diamino acids with different protecting groups on each amino group. The process benefits from the versatile bifunctional thiourea catalysts, which effect the formation of these products in high yields and stereoselectivities.

Organocatalytic SOMO reactions of copper(I)-acetylide and alkylindium compounds with aldehydes

The derivatisation of aldehydes in their α-position is an important facet of organic synthesis. Organocatalytic radical reactions afford α-functionalised aldehydes via a SOMO activation pathway. New organo-SOMO reactions of aldehydes with copper(I)-acetylide and alkylindium reagents are detailed. These reactions proceed well under the catalysis of chiral imidazolidinones. The corresponding functionalised aldehydes were obtained with acceptable yields, but with only low enantiomeric ratios.

Methyltrioxorhenium-catalysed oxidation of secondary amines to nitrones in ionic liquids

Nitrones serve as starting materials for the synthesis of many heterocycles. Oxidation of secondary amines using hydrogen peroxide and the catalytic amount of methyltrioxorhenium in ionic liquids is a useful method for the preparation of nitrones. Ultrasonic irradiation and ionic liquids have a positive influence on the reaction. The nitrones required were isolated in good yields. Corresponding hydroxylamines, which can be easily oxidised to nitrones, often accompanied the main products. Methyltrioxorhenium in ionic liquids was re-used in several reaction cycles without any deteriorating effect on the course of the reaction.

Asymmetric Copper-catalyzed 1,4-Additions and Allylic Substitutions with Nucleophiles Formed by the Hydrometalation of Alkenes

The need for enantiomerically pure pharmaceuticals, agrochemicals, food additives, and other chiral compounds propels research in the area of asymmetric catalysis. Metal catalyzed 1,4-addition and allylic substitution of organometallic nucleophiles to Michael acceptors are among the principal transformations for the synthesis of chiral compounds, applicable also at industrial scale. Typically, complexes of soft transition metals, such as copper, and rhodium, are used to catalyze these reactions. Particularly copper-catalyzed conjugate addition and allylic substitution share a number of common features, because they have similar transition states. A variety of nucleophiles can be employed, such as organolithium, Grignard, organozinc, organoaluminium, organoboron, and other reagents. However, the majority of these reagents have to be synthesized prior to conjugate addition or allylic substitution itself. In addition, these reagents are usually highly reactive and do not tolerate many common functional groups. Practical applications limit also their sensitivity to air and moisture or the necessity to work at low temperatures. Therefore, a method that would enable convenient formation of benign organometallic species from simple and inexpensive precursors, and be compatible with metal-catalyzed asymmetric 1,4-conjugate addition, would be of great value. Alkenes are the simplest and most convenient sources of carbon synthons. So, are there any methods available to transform them into suitable organometallic reagents applicable to asymmetric metal-catalyzed conjugate additions? One can think of numerous hydrometalation or carbametalation reactions, which are quite common among organometallic compounds. However, only some of them are of practical synthetic value. Furthermore, in comparison to hydrometalations of alkynes, which leads to alkenyl metal species, alkene hydrometalations often suffer from rapid b-hydride elimination, a reverse reaction to hydrometalation. Therefore the choice of suitable hydrometalating reactions, applicable to alkenes, is limited to hydroboration and hydrozirconation. Although both of these reactions have been known for long time, their utilization for in situ generation of sp carbon nucleophiles for asymmetric 1,4-addition reaction or allylic alkylation has been unknown. There is, undoubtedly, great synthetic potential in this methodology, as it considerably broadens the scope of these asymmetric transformations. The primary reason is that other sp-hybridized carbon nucleophiles such as organolithium, Grignard, organoaluminium, or dialkylzinc reagents are very reactive and, thus, have low tolerance for many functional groups. Another important feature of this approach is increased effectiveness in terms of step economy, because required organometallic reagent is prepared in situ or at least without the need for its isolation and purification. Therefore, combination of hydrometalation of alkenes with enantioselective Cu-catalyzed 1,4-addition and allylic substitution constitutes an important advance in the field of asymmetric catalysis (Scheme 1).