Asymmetric catalysis

The preparation of 2-triazolyl- and 2-triazolylmethylpyrrolidines from L-proline and L-trans-4-hydroxyproline is described, along with their evaluation as chiral ligands in ruthenium-catalyzed asymmetric transfer hydrogenation. Modular evolution of the ligands by introduction of remote substituents is also presented, showing a surprisingly important effect on the performance of the ligands.

The synthesis of new modular chiral diphosphite ligands with C 2 -symmetry and carbohydrate backbone is reported. We also report here the synthesis of the corresponding rhodium complexes [RhA C H T U N G T R E N N U N G (COD)(L)]BF 4 (L = diphosphite). All these species have been characterised in solution by NMR spectroscopy and in some cases in the solid state by X-ray diffraction. The solution structures of the hydridorhodiumcarbonyl species [RhH(CO) 2 (L)], where L = diphosphites 12a-14a, 12b, have been studied using high-pressure NMR spectroscopy. The configuration and substitution of the remote stereo-centres in positions 2 and 5 of the tetrahydrofuran ring of the diphosphite ligands were observed to have a considerable influence on the results obtained in the rhodium-catalysed hydroformylation and hydrogenation reactions. Thus, the configuration of the major isomer obtained in the hydroformylation reaction may be controlled by changing the configuration of these stereocentres.

Enantioselective syntheses O 0031 Copper-Catalyzed Enantioselective Conjugate Addition of Grignard Reagents to α,β-Unsaturated Esters. -(LOPEZ, F.; HARUTYUNYAN, S. R.; MEETSMA, A.; MINNAARD, A. J.; FERINGA*, B. L.; Angew. Chem., Int. Ed. 44 (2005) 18, 2752-2756; Dep. Org. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.; Eng.) -Nuesgen 35-035

A family of enantiomerically pure ligands based on the cyclobutenedione structure, and containing either an enantiomerically pure amino alcohol or a diamine as the chiral element, has been synthesized. As first examples of their application, these versatile and modularly constructed ligands have been tested in the transfer hydrogenation of acetophenone and in the reduction using borane of this same substrate.

We reported recently that Schiff base 1 (Figure 1) is a remarkably general catalyst for the hydrocyanation of aldimines [1] and ketoimines, [2] producing Strecker adducts in >90% ee for most substrates examined (Equation 1). [3] This catalyst was identified and optimized from a parallel library of Schiff base derivatives that was synthesized and screened on solid phase. [1,4]

It is no longer necessary to use dialkylzinc reagents to obtain enantioselectivities >95% in the copper-catalyzed asymmetric conjugate addition of organometallic compounds to cyclic enones. We now report how this can be accomplished by using inexpensive and readily available Grignard reagents. Screening of bidentate ligands provided outstanding results with copper complexes of commercially available chiral ferrocenyl-based diphosphines, in particular TaniaPhos and JosiPhos derivatives. These catalysts tolerate a range of Grignard reagents and different cyclic enones as substrates, leading to high regioselectivities and unprecedented enantioselectivities. Moreover, the reactions are successful with moderate catalyst loading (5 mol %) under mild conditions and in the absence of additives.

The first decade of the 21 st century evidenced the explosive growth of homogeneous gold catalysis. The unique versatility and efficiency of gold metal complexes are clearly indicated by the numerous reports regarding their application in various organic transformations. Key to the success of homogeneous gold catalysis is the ability of gold(I) and gold(III) to act as soft carbophilic Lewis acids towards CÀC multiple bonds. This high carbophilicity translates to a relatively low oxophilic character and a kinetically labile carbon-metal bond, which allows efficient catalyst turnover. In addition, the high oxidation potential between gold(I) and gold(III) makes the gold catalysts inert from air oxidation. Therefore, compared with other transition metal catalysts, gold complexes could catalyze reactions under very mild conditions (tolerates air or moisture), giving excellent chemoselectivity, wide functional group compatibility and high efficiency.

To generalize the use of heterogeneous asymmetric catalysis we developed a new process to produce L L-DOPA via cinchonine mediated Pd/C asymmetric reduction of the corresponding cinnamic acid precursor. Reaction proceeded well giving rise to good optical yield (44%). The use of O,O 0 -dibenzyl groups in the substrate appears to be the key to this optical purity and deserves further investigation.

The key to waste minimization in fine chemicals manufacture is the widespread substitution of classical organic syntheses employing stoichiometric amounts of inorganic reagents with cleaner, catalytic alternatives. The E factors (by waste per kg product) of chemical processes increase dramatically on going downstream from bulk to fine chemicals and pharmaceuticals, mainly owing to the use of "stoichiometric" methods. The concept of atom efficiency is a useful tool for rapid evaluation of the amount of waste generated by alternative processes. The general theme of atom-efficient, catalytic processes is illustrated with industrially relevant examples. These include catalysis by solid acids and bases, catalytic reductions and oxidations, catalytic C-C bond formation, asymmetric catalysis, biocatalysis, and catalysis in novel media (aqueous and fluorous biphasic systems, supercritical fluids, and ionic liquids).

The use of fluorinated alcohols as solvents, cosolvents or additives in homogeneous catalysis is reviewed. The effect of these particular compounds on efficiency, regioselectivity and stereoselectivity of metal-catalyzed reactions, as well as on reactions mediated by organocatalysts, is described. Where available in several cases, the effect of fluorous alcohols on the catalytic mechanism is analyzed in detail and rationalized by their unique physical and chemical properties. In most instances, a comparison to the effect of commonly employed solvents is elaborated. 1 Introduction 2 Physical Properties of Fluorinated Alcohols 3 Applications in Homogeneous Catalysis 3.

The activity and stability under flow conditions of covalently and non-covalently silica supported proline and proline-like organocatalysts is herein described. The slow aldol reaction of cyclohexanone with pnitro benzaldehyde and the fast a-amination of isovaleraldehyde with dibenzyl azodicarboxylate have been selected as model reactions for this study. Prospects and limitations of the disclosed continuousflow organocatalytic approach are widely discussed.

Starting from inexpensive L-(+)-tartaric acid, it was possible to resolve and obtain pure both enantiomers of trans-cyclohexane-1,2-diamine 1 and thence both enantiomers of BINOL 2, two of the most powerful, chiral inducing backbones in asymmetric catalysis. The modified method is very economic, not only due to an almost doubling of the overall yields of enantiomerically pure compounds (86% 1, 83% 2) but also due to the easy recovery of resolving agent 1 [66% (R,R)-1, 79% (S,S)-1] in the BINOL resolution. An improvement in the yield of the preparation of racemic BINOL is also recorded.

Chemistry and pharmacological activity of various types of Mannich bases and their derivatives were well documented. A survey of the literature revealed extensive studies on the synthesis and reactivity of Mannich bases derived from ketones, amides, enamines, phenols and indoles of widely different structures, while comparatively little attention has been given to Mannich bases derived from nitroalkanes and related nitrocompounds. Mannich reactions using nitroalkanes and related compounds as substrates are of synthetic relevance and the products are promising as biologically active substances. It is known that the nitro group is an important constituent of many biologically significant heterocycles such as antibiotic drugs (nitrofurantoin and nitrofurazone). A number of nitro-heterocycles of pharmacological interest were also synthesized by Mannich reactions with suitable nitro-substrates. In view of this, and because of the widespread and increasing interest in the chemistry of Mannich bases, the present work is concerned with attempts to extend the scope of Mannich reactions with nitroalkanes to include the synthesis of a variety of nitro N-and S-heterocycles.

The octane enhancement of light straight run naphtha is one of the significant solid acid catalyzed processes in the modern oil refineries due to limitations of benzene, aromatics, and olefin content in gasoline. This paper aims to examine the role of various catalysts that are being utilized for the isomerization of light naphtha with an ambition to give an insight into the reaction mechanism at the active catalyst sites, and the effect of various contaminants on catalyst activity. In addition, different technologies used for isomerization process are evaluated and compared by different process parameters.

Enantioselective organocatalytic asymmetric Diels-Alder reactions provide a facile and efficient route to optically active functionalized cyclohexenes, which can be further transformed into a variety of important organic compounds. A variety of small organic molecules such as prolines, imidazolidinones, chiral Brønsted acids, guanidines, carbenes and Cinchona alkaloids can be used as different catalyst systems to induce enantioselectivity in the reaction. This review provides an overview of the history of the asymmetric organocatalyzed Diels-Alder reaction.

This review covers asymmetric organocatalytic methods leading to the enantioselective synthesis of carbocyclic and heterocyclic compounds, focusing on synthetically useful protocols, and is organized according to the different types of synthetic procedures affording cyclic frameworks: organocatalytic desymmetrizing cyclizations of prochiral substrates, in which at least one of the newly created stereogenic centers arises as a result of the desymmetrization, are discussed on the first place.

a,a-DiarylA C H T U N G T R E N N U N G (dialkyl)prolinol ethers constitute a potent organocatalyst family which has been shown to be very general for a broad range of reactions involving enamine and iminium ion activation or a combination of both. The reactions are characterized by an efficient steric control approach and can lead to a variety of a-, b-, g-, and a,b-functionalized carbonyl compounds with excellent stereocontrol. As a full expression of their catalytic activi-ty, these compounds are also excellent promoters of elegant cascade processes and valuable catalysts in watercompatible systems. Scheme 1. Organocatalyzed enantioselective anti-Mannich reaction of aldehydes with glyoxylate-derived imines. Scheme 2. Enantioselective aminomethylation reaction of aldehydes. Scheme 3. Enantioselective a-arylation of aldehydes with quinones. Scheme 4. a-Allylic alkylation of aldehydes. Scheme 5. Conjugate addition of aldehydes to nitroalkenes. Scheme 6. Conjugate addition of aldehydes to vinyl ketones catalyzed by 2, 5, and 6. Scheme 7. Conjugate addition of aldehydes to maleimides. 926 www.chemasianj.org Scheme 39. Organocatalytic asymmetric synthesis of 5-hydroxypyrrolidines and 3-substituted proline derivatives. Scheme 40. Organocatalytic Michael/Morita-Baylis-Hillman reaction. Scheme 41. The concept of iminium-enamine activation in domino processes for a,b-functionalization.

A new series of Schiff bases derived from Cinchona alkaloids were developed as chiral ligands for the copper(II)-catalyzed asymmetric Henry reaction. The optimized catalyst can promote the Henry reaction of both aromatic and aliphatic aldehydes with nitromethane or nitroethane. Those reactions can afford the chiral b-nitro alcohol adducts with high enantioselectivities.

A series of enantiopure ligands based on the aminoindanol scaffold, but differing in regio-and stereochemistry has been synthesized. These ligands have been conveniently derivatized and their catalytic efficiency in different enantioselective reactions has been screened to determine privileged candidates with respect to regio-and stereochemistry for each considered process. The nature of the amino substituent has been optimized for specific applications and this has led to the development of an efficient method for the preparation of bulky bicyclic amines by reductive amination.

The synthesis of the dihydrochloride salts of (R)-1 and (S)-1 2-(aminomethyl)piperidine is reported starting from either (S) or (R) lysine, respectively. A key step in the synthetic protocol involves the in situ formation of aziridinium 8, which then undergoes an intramolecular ring opening with concomitant piperidinium ring formation, in a stereoselective manner. The route offers a practical synthesis of (R)-1 and (S)-1, and it should make them more accessible for exploration in asymmetric catalysis or as building blocks in pharmaceutical research.

The design and the synthesis of a set of new chiral hydroxyalkyl-and hydroxyaryl-chelating diaminocarbene ligands is reported. Comparative catalytic studies show the importance of the scaffold design around the NHC unit to obtain a high enantiocontrol in Cu-catalyzed asymmetric conjugate addition (ACA). Whereas low selectivities are observed when the stereogenic centre is placed within the N-

The 4-nitrophenyl ether is an efficient directing group in the asymmetric aminohydroxylation reaction of homoallylic ether derivatives. Either regioisomeric product can be obtained with useful levels of enantioselectivity allowing for the short enantioselective synthesis of GABOB and homoserine derivatives. A model based on substrate-catalyst interactions is presented to explain the regio-and enantioselectivity of the aminohydroxylation reactions.

Dedicated to Professor Carmen N ajera on the occasion of her 60th birthday a b s t r a c t Asymmetric organocatalytic additions of anthrones to activated alkenes are discussed. The reaction between anthrone or dithranol and a,b-unsaturated aldehydes is catalyzed by diphenylprolinol trimethylsilyl ether in toluene at À40 C, giving the Michael adducts with good yields and enantioselectivities. Bifunctional amino-thioureas efficiently catalyze the additions of anthrones to both nitroalkenes and maleimides, and high enantioselectivities can be achieved in both instances at room temperature. In the case of nitroalkenes, a Michael addition takes exclusively place. Anthrone generally gives DielseAlder cycloadducts in the reaction with maleimides, while dithranol affords the Michael adducts. Transition state working models in which the bifunctional catalyst binds simultaneously to the alkene and to the anthrone enolate account for the stereochemical outcome of these additions.

A family of eight neutral, pseudotetrahedral piano-stool ruthenium complexes C, of the type [RuCl 2 (pcymene)(PArPhR)] (Ar ¼ 1-naphthyl, 9-phenanthryl and 2-biphenylyl; R ¼ Me, i-Pr, OMe, eCH 2 SiMe 3 and eCH 2 SiPh 3 ) have been prepared and characterised, including the X-ray crystal structure for C6 (Ar ¼ 2-biphenylyl; R ¼ i-Pr). These complexes catalyse the asymmetric hydrogen transfer reaction of acetophenone in refluxing 2-propanol in the presence of potassium tert-butoxyde, reaching full conversions and up to 45% ee after 24 h towards the S enantiomer of 1-phenylethanol. Cationic complexes formed upon treatment of C with one equivalent of AgSbF 6 or (Et 3 O)PF 6 are active in the cyclopropanation reaction of styrene and a-methylstyrene by ethyl diazoacetate. Low to moderate conversions (up to 58%), diastereoselectivities (up to 40% de), and moderate enantioselectivities (up to 69% ee) have been found. For both reactions, bulky complexes and C6 in particular lead to the best results.

Asymmetric allylation of aromatic aldehydes 1 with allyltrichlorosilane (2) can be catalyzed by new terpene-derived bipyridine N,N 0 -dioxides 12-15 and an axially chiral biisoquinoline dioxide 17b with good enantioselectivities. Dioxides have been found to be more reactive catalysts than their monooxide counterparts.

CITATIONS 91 READS 102 6 authors, including: Some of the authors of this publication are also working on these related projects: Metal and chemical hydrides as hydrogen (energy) storage materials View project Yaroslav Filinchuk Université Catholique de Louvain 244 PUBLICATIONS 5,991 CITATIONS SEE PROFILE All content following this page was uploaded by Yaroslav Filinchuk on 28 December 2016.

The synthesis of a variety of new 4,5-disubstituted [2.2]paracyclophane derivatives has been achieved employing different crosscoupling reactions. By this methodology, a heteroatom-variation of successful catalyst ligands was achieved, giving rise to a modular ligand system. The X-ray structure of 4-hydroxy-5-(1 0 -hydroxy-1 0 -phenylethyl)-[2.2]paracyclophane was determined to elucidate the configuration. Additionally, a diastereoselective synthesis of planar-and central-chiral 4-([2.2]paracyclophanyl)ethylamine was achieved, thus resulting in a planar-and central-chiral phenyl ethylamine analogue.

The enantioselective addition of allylstannanes to glyoxylates and glyoxals, as well as simple aromatic and aliphatic aldehydes, catalyzed by chiral (salen)Cr(III) complexes, has been studied. The reaction proceeded smoothly for the reactive 2-oxoaldehydes and allyltributyltin in the presence of small amounts (1-2 mol %) of (salen)Cr(III)BF 4 (1b) under mild, undemanding conditions. However, in the case of other simple aldehydes, the use of high-pressure conditions is required to obtain good yields. Classic chromium catalyst 1b, easily prepared from the commercially available chloride complex 1a, affords homoallylic alcohols usually in good yield and with enantiomeric purity of 50-79% ee. The stereochemical results are rationalized on the basis of the proposed model.

A new class of chiral C2-symmetric dipyridylmethane ligands was prepared from naturally occurring monoterpenes, according to a method based on a double Michael–azaannellation–aromatization sequence. These ligands were assessed in the enantioselective palladium-catalyzed allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethylmalonate and in the copper-catalyzed cyclopropanation of styrene with ethyl diazoacetate. Enantioselectivity up to 88% ee was obtained.

The first example of a highly enantioselective organocatalytic aziridination of a-substituted a,b-unsaturated aldehydes is presented. The reaction is catalyzed by simple chiral amines and gives access to highly functional terminal azirdines containing an a-tertiary amine stereocenter in high yields and enantiomeric ratios (95.5:4.5-98:2).

Synthesis. -A novel enantiopure 4-aminopyridine catalyst is developed and applied to the kinetic resolution of secondary aryl alcohols. -(NGUYEN, H. V.; MOTEVALLI, M.; RICHARDS*, C. J.; Synlett 2007, 5, 725-728; Sch. Biol. Chem. Sci., Queen Mary Westfield Coll., London E1 4NS, UK; Eng.) -Mais 29-030

vided by the polymer backbone have shown a synergistic effect, which has led to remarkably high catalytic activity and enantioselectivity. [5a-g] Catalysis mediated by primary or secondary amines include reactions that take place via enamine and iminium ion intermediates. Among these processes, Michael reactions represent a powerful synthetic tool for the assembly of 1,5difunctionalized compounds (Scheme 1). Within the wide application range of these chemical transformations, their use as the first step in cascade processes, or use of a combination of the two catalysis mechanisms in tandem sequences, has aroused a great deal of interest because complex molecular frameworks can be constructed in simple, one-pot operations. Of particular interest are catalysts derived from (S)-a,a-diarylprolinol silyl ethers, independently introduced by Jørgensen and Hayashi for the enantioselective organocatalyzed a-sulfenylation of aldehydes and asymmetric Michael addition of aldehydes to nitroalkenes, respectively. The steric effect caused by the bulky substituent placed at C2 on the pyrrolidine ring controls the enantioselectivity of the reactions very efficiently.

We report on the synthesis, metal coordination, and catalytic impact of histidylidene, a histidine-derived N-heterocyclic carbene (NHC) ligand. The histidinium salt 3, comprising methyl substituents at both heterocyclic nitrogens and protected at the C-and N-terminus of the amino acid, was rhodated and iridated by a transmetallation protocol using Ag 2 O. Ambient temperature and short reaction times were pivotal for full retention of configuration at the α-carbon. The stereospecificity of the reaction was conveniently probed by 31 P NMR spectroscopy after transmetallation with rhodium(I) and coordination of enantiopure (S)-Ph-binepine. The histidylidene rhodium complexes are highly efficient catalysts for the mild hydrosilylation of ketones. For the cationic complexes [Rh(cod)(histidylidene)( phosphine)] + , lowering the temperature shifted the rate-limiting step of the catalytic reaction to an earlier stage that is not enantioselective. Hence the asymmetric induction-which is governed by the chiral phosphine-did not improve at low temperature.

Dedicated to Professor Wolfgang A. Herrmann on the occasion of his 60th birthday Noteworthy efforts have been devoted to the development of efficient catalytic asymmetric reductions employing benign and environmentally available biometals such as iron, zinc, and copper. The preparation of enantiomerically pure secondary alcohols is of special significance because these intermediates constitute valuable building blocks for the manufacture of pharmaceuticals, agrochemicals, and advanced materials. Catalytic asymmetric hydrogenation of prochiral ketones is the most direct route to optically active alcohols, however, hydrosilylation of carbon-carbon and carbonheteroatom bonds is a promising alternative to asymmetric hydrogenation because of the mild conditions and operational simplicity. The earliest reports on hydrosilylation appeared three decades ago, and known asymmetric hydrosilylations of prochiral ketones rely on precious metals such as rhodium, ruthenium, and iridium. Less expensive metals such as titanium, zinc, tin, and copper have also been explored. Each method has its virtues as well as its limitations. The limitations include either the cost of the metal catalyst, the toxicity of the residual metal in the product, the operational difficulties (e.g. low temperatures ranging from À50 to À70 8C), or the use of complex ligand systems.