Metal-catalyzed reactions asymmetric

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

Pu and co-workers incorporated atropisomeric binaphthols in polymer matrixes constituted of binaphthyl units, the macromolecular chiral ligands obtained being successfully used in numerous enantioselective metal-catalyzed reactions,97-99 such as asymmetric addition of dialkylzinc reagents to aldehydes.99 Recently, they also synthesized a stereoregular polymeric BINAP ligand by a Suzuki coupling of the (R)-BINAP oxide, followed by a reduction with trichlorosilane (Figure 10).100... 

If kinetic resolution is being studied, the ratio of pseudo-e nantiomers can be measured by MS, allowing for the determination of ee-values (and/or of selectivity factors E). The same applies to the reaction of pseudo prochiral compounds. This system has been used successfully in the directed evolution of enantioselective enzymes. However, it should work equally well in the case of asymmetric transition metal catalyzed reactions. In the original version about 1,000 ee-deter-minations were possible per day (Figure 6).94 The second-generation version based on an 8-channel multiplexed spray system enables about 10,000 samples to be handled per day, the sensitivity being 2% ee.96... 

The use of chiral copper complexes in asymmetric synthesis was inaugurated in 1966 when the first homogeneous asymmetric metal-catalyzed reaction was reported a copper catalyzed cyclopropanation (2). At the end of 1999, more than 25 distinct reactions were reported wherein the use of a chiral copper complex had induced an enantioselective transformation. The field grew quickly and the best is most likely yet to come. 

The seminal report of an asymmetric homogeneous metal-catalyzed reaction described the copper-catalyzed group-transfer reaction from a diazoester to an alkene, Eq. 3 (2). This article provided experimental verification of the intervention of copper carbenoid olefin complexes in the catalytic decomposition of diazo com-... 

A diverse group of secondary and tertiary amines are readily synthesized from the reaction of primary and secondary amines with allylic carbonates in the presence of preformed iridium metalacycles, but the direct synthesis of primary amines via iridium-catalyzed allylic amination requires the use of ammonia as a nucleophile. The asymmetric allylation of ammonia had not been reported until very recently, and it is not a common reagent in other metal-catalyzed reactions. Nonetheless, Hartwig and coworkers developed the reactions of ammonia with allylic carbonates in the presence of la generated in situ [89]. Reactions conducted in the initial work led exclusively to the products from diallylation (Scheme 16). Further advances in... 

Carbon-carbon bond-forming reactions are one of the most basic, but important, transformations in organic chemistry. In addition to conventional organic reactions, the use of transition metal-catalyzed reactions to construct new carbon-carbon bonds has also been a topic of great interest. Such transformations to create chiral molecules enantioselectively is therefore very valuable. While various carbon-carbon bond-forming asymmetric catalyses have been described in the literature, this chapter focuses mainly on the asymmetric 1,4-addition reactions under copper or rhodium catalysis and on the asymmetric cross-coupling reactions catalyzed by nickel or palladium complexes. 

In addition to metal catalysts, organocatalysts could also be used in asymmetric cyanation reactions. Chiral Lewis bases, modified cinchona alkaloids, catalyzed asymmetric cyanation of ketones by using ethyl cyanoformate as the cyanide source (Scheme 5.34)." Similar to metal-catalyzed reactions, ethyl cyanoformate was first activated by chiral Lewis bases to form active nucleophiles. Various acyclic and cyclic dialkyl ketones were transformed into the desired products. Because of using... 

The development within the area of asymmetric 1,3-dipolar cycloadditions since the first edition of this series is too extensive to be completely covered in this chapter and we have therefore chosen selected examples to illustrate the different aspects of the subject. The examples have been chosen on the basis of general importance and also to complement recent monographs in the area. Special attention will be given to recent developments within the area of metal-catalyzed reactions. Intramolecular 1,3-dipolar cycloadditions are only briefly described. 

The development and application of catalytic enantioselective 1,3-dipolar cycloadditions is a relatively new area. Compared to the broad application of asymmetric catalysis in carbo- and hetero-Diels-Alder reactions (337,338), which has evolved since the mid-1980s, the use of enantioselective metal catalysts in asymmetric 1,3-dipolar cycloadditions remained almost unexplored until 1993 (5). In particular, the asymmetric metal-catalyzed reactions of nitrones with alkenes has received considerable attention during the past 5 years. 

Mark Elliott was born in Doncaster. He studied in Loughborough, where he obtained a BSc in 1991 and a PhD in 1994 working with Prof. C. J. Moody on transition-metal-catalyzed reactions of diazo compounds. After postdoctoral work with Prof A. Pfaltz, initially in Basel under the auspices of a Royal Society European Exchange Fellowship, and later at the Max-Planck Institute in Miilheim, he returned to the UK in 1996 to take up his current position as lecturer in chemistry at Cardiff His reseach interests include asymmetric heterocyclic chemistry, asymmetric catalysis, and natural product chemistry. 

Because vicinal diamines and 2-aminoalcohols are important components of natural products and medicinal agents, and used as ligands for metal-catalyzed reactions, especially in asymmetric synthesis, efficient methods for the compounds have been extensively investigated over the past decade. " ... 

The advancements in supramolecular catalysis are not limited to transitions-metal catalyzed reactions. Clarke and coworkers recently reported the preparation of a library of organocatalysts and their application in the asymmetric Michael addition of ketones to nitroalkenes [37]. They proposed use of a supramolecular catalyst formed... 

T. Hayashi and M. Kumada, Asymmetric Coupling Reactions, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 5, Chap. 5, Academic Press, New York, 1985 J. C. Fiaud, Mechanisms in Stereo-Differentiating Metal-Catalyzed Reactions. Enantioselective Palladium-Catalyzed Allylation, in A. F. Noels, M. Graziani, and A. J. Hubert, eds., Metal Promoted Selectivity in Organic Synthesis, p. 107, Kluwer Academic, Dordrecht, 1991. 

The range of alkenes that may be used as substrates in these reactions is vast Suitable catalysts may be chosen to permit use of ordinary alkenes, electron deficient alkenes such as a,(3-unsaturated carbonyl compounds, and very electron rich alkenes such as enol ethers. These reactions are generally stereospecific, and they often exhibit syn stereoselectivity, as was also mentioned for the photochemical reactions earlier. Several optically active catalysts and several types of chiral auxiliaries contained in either the al-kene substrates or the diazo compounds have been studied in asymmetric cyclopropanation reactions, but diazocarbonyl compounds, rather than simple diazoalkanes, have been used in most of these studies. When more than one possible site of cyclopropanation exists, reactions of less highly substituted alkenes are often seen, whereas the photochemical reactions often occur predominantly at more highly substituted double bonds. However, the regioselectivity of the metal-catalyzed reactions can be very dependent upon the particular catalyst chosen for the reaction. 

Novel methods for functionalizing piperidines at the 3- and 4-positions were also introduced. Mete and co-worker synthesized 3-diazo-piperidin-2-one and characterized its reactivity in transition-metal catalyzed reactions, particularly H-X insertion reactions and cyclopropanation reactions <02T3137>. Christoffers and co-workers developed an asymmetric Michael addition reaction with a chirally modified 4-piperidone-enamine. They were able to create a quaternary carbon center in >95% de and elaborate the compound on through classical means to the functionalized piperidine 107 (Scheme 21) <02EJ01505>. 

Asymmetric reaction is one of the most exciting features of catalyzed hydroboration since optically active phosphine ligands are the chiral auxiliaries most extensively studied for metal-catalyzed reactions (Scheme 13).134 The chiral ligands used for asymmetric hydroboration of alkenes include BINAP,136 1 03-106,167-170 QUINAP,171-173 107-109,172,174-176 and BDPP.177,178... 

In addition, the reader may realize that axis of rotation can still be present in some chiral Cp-metal complexes (e.g., a C2 axis in the enantiomeric forms in 22 and 23, a C5 axis in 24). With rotation axes present the systems are not asymmetric, only dissymmetric (i.e., lacking mirror symmetry). This is, however, sufficient to induce the existence of enantiomeric forms (218). Moreover, it is known from numerous examples that chiral ligands with C2 symmetry can provide for a higher stereoselectivity in (transition metal-catalyzed) reactions than comparable chiral ligands with a total lack of symmetry. The effect is explained by means of a reduced number of possible competing diastereomeric transition states (218). Hence, rotational symmetry elements may be advantageous for developing useful Cp-metal-based catalytic systems. 

In this review, we have shown the major advances in the growing field of cascade chemistry that have led to regio-, chemo-, and stereoselective formation of several new carbon-carbon and carbon-heteroatom bonds in a stepwise economical fashion by using transition metal-catalyzed reactions. These approaches have already allowed very impressive and rapid construction of unnatural and natural polycyclic compounds of very high molecular complexity. These initial achievements should stimulate the synthetic community to pursue further works notably to develop more efficient and selective strategies that involve new generations of versatile catalysts. Next endeavors will have to focus on green processes as well as asymmetric catalysis. 

Enantioselective catalysis exemplifies how a complex synthetic route to a chiral molecule can be simplified by catalytic methods, reducing the overall amount of waste and increasing yields. Only a few of the metal-catalyzed reactions have yet been applied industrially, mostly for the synthesis of pharmaceuticals, vitamins, agrochemicals, flavours and fragrances. They include, asymmetric oxidation, hydrogenation, isomerization, hydroformylation, and cyclopropanation (Chapters 2, 3, 4 and 5 Sections 2.7, 3.5, 3.6, 3.7, 4.6.7, 5.6). 

Oxidation is still less well developed than other metal-catalyzed reactions but the application is a very important one practically, so efforts are continuing. The mechanisms are hard to decipher, often being radical in character, but selective nonradical oxidations are becoming much more common. Asymmetric versions of oxidation catalysts have now appeared that have become very useftil in organic synthetic and commercial applications. 

Recent advances of the preparation of novel optically active organoselenimn compounds, mainly organic diselenides, and their application as chiral ligands to some transition metal-catalyzed reactions and also as procatalysts for asymmetric diethylzinc addition to aldehydes are reviewed. Recent results of catalytic reactions using some organoselenimn compounds such as aUylic oxidation of alkenes and its asymmetric version as well as epoxidation of alkenes are also summarized. 

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