Chiral catalysts: overview

During our research in this field of small-ring heterocycles we found that functionahzed aziridines are attractive chiral catalysts, e.g., in the diethylzinc addition to aldehydes. Aspects of such uses of aziridines will be discussed as well. This overview does not pretend to be an exhaustive coverage of all existing literature on small-ring aza-heterocycles as that would require a separate monograph. Instead, emphasis is put on functionahzed three-membered aza-heterocycles, that were investigated in the author s laboratory [1], and relevant related literature. The older literature on these heterocycles is adequately summarized in some extensive reviews [2]. Chiral aziridines have been reviewed recently by Tanner [3], by Osborn and Sweeney [4], and by McCoull and Davis [5]. 

Asymmetric catalysis is a vital and rapidly growing branch of modern organic chemistry. Within this context, Ti- and Zr-based chiral catalysts have played a pivotal role in the emergence of a myriad of efficient and enantioselective protocols for asymmetric synthesis. In this chapter, a critical overview of enantioselective reactions promoted by chiral Zr-based catalysts is provided. Since an account of this type is most valuable when it provides a context for advances made in a particular area of research, when appropriate, a brief discussion of related catalytic asymmetric reactions promoted by non-Zr-based catalysts is presented as well. 

For general overviews on polymer-supported catalysis, see a) Chiral Catalyst Immohilization and Recycling (Eds. D. E. DeVos, I. F. ). Vankelecom,... 

In order to place later chapters in proper context, the first chapter offers a comprehensive overview of industrially important catalysts for oxidation and reduction reactions. Chapters 2 and 3 describe the preparation of chiral materials by way of the asymmetric reduction of alkenes and ketones respectively. These two areas have enjoyed a significant amount of attention in recent years. Optically active amines can be prepared by imine reduction using chiral catalysts, as featured in Chapter 4, which also discloses a novel reductive amination protocol. 

Enantioselective synthesis is a topic of undisputable importance in current chemical research and there is a steady flow of articles, reviews and books on almost every aspect involved. The present overview will concentrate on the application of solid chiral catalysts for the enantioselective synthesis of chiral molecules which are a special class of fine chemicals. Included is an account on our own work with the cinchona-modified Pt catalysts. Excluded is the wide field of immobilized versions of active homogeneous complexes or of bio-catalysts. During the preparation of this survey, several reviews have been found to be very informative [1-14]. 

In summary, the C-H insertion chemistry of rhodium carbenoids is a very powerful method for transformation of C-H bonds. Highly regioselective and stereoselective reactions are possible and several classes of chiral catalyst are capable of very high asymmetric induction. The chemoselectivity in this chemistry is exceptional, as illustrated by the numerous intermolecular and intramolecular reactions described in this overview. Most notably, this chemistry offers new and practical strategies for enantioselective synthesis of a variety of natural products and pharmaceutical agents. 

In particular, reduction of unsymmetric ketones to alcohols has become one of the more useful reactions. To achieve the selective preparation of one enantiomer of the alcohol, chemists first modified the classical reagents with optically active ligands this led to modified hydrides. The second method consisted of reaction of the ketone with a classical reducing agent in the presence of a chiral catalyst. The aim of this chapter is to highlight one of the best practical methods that could be used on an industrial scale the oxazaborolidine catalyzed reduction.1 1 This chapter gives an introductory overview of oxazaborolidine reductions and covers those of proline derivatives in-depth. For the oxazaborolidine derivatives of l-amino-2-indanol for ketone reductions see Chapter 17. 

This article provides a brief overview of the recently developed diversity-based approaches in the screening and identification of effective metal-based chiral catalysts for enantioselective synthesis. This first wave of reports indicates... 

A concise overview of recycling modes for chiral catalysts, including enzymes, is given by Kragl et al. [15]. The technical aspects of the application of continuously operated chemical membrane reactors was covered by Woltinger et al. [16, 17]. 

A review of enantioselective hydrogenation of enamines (including A-acyl enamines and unfunctionalized enamines and imines including A-aryl/alkylimines and activated imines and N-H imines, which are poor substrates because of their electron-rich nature) using chiral Rh-, Ru-, Ti-, and Ir-catalysts and some other chiral catalysts has been published it provides an overview for the synthesis of chiral amines and focuses on the development of chiral metal catalysts for such transformations ... 

From this short overview it appears that the majority of the recent studies on enantioselective cycloisomerizations have been focused so far on asymmetric Alder-ene type cyclizations with Pd and Rh catalysts, since these reactions represent an economical access into synthetically usefiil cyclopentene and cyclohexene frameworks (Sects. 10.2.1 and 10.3.1). For these processes, efficient chiral catalysts have been afforded mainly by atropisomeric diphosphines, but also DuPHOS, Skewphos and phosphine-oxazolines can occasionally represent suitable auxiliaries. 

Abstract After an overview of chiral urea and thiourea synthetic methods, this review describes the main applications of urea and thiourea complexes in asymmetric catalysis. Some recent examples of thioureas as catalysts are also presented. Coordination chemistry of ureas and thioureas is briefly discussed. 

An overview of the catalytically active M-L systems is presented in terms of both achiral and chiral reactions. Where deemed appropriate, reference is also made to organometallic and organolanthanide catalysts, as well as (briefly) H—X addition to C=0. 

Abstract An overview of the area of organocatalytic asymmetric acyl transfer processes is presented inclnding O- andiV-acylation. The material has been ordered according to the structnral class of catalyst employed rather than reaction type with the intention to draw mechanistic parallels between the manner in which the varions reactions are accelerated by the catalysts and the concepts employed to control transfer of chiral information from the catalyst to the substrates. 

An overview of the results of the enantioselective sulfoxidation utilizing various chiral metal catalysts is given in Table 28. 

Enantioselective catalytic alkylation is a versatile method for construction of stereo-genic carbon centers. Typically, phase-transfer catalysts are used and form a chiral ion pair of type 4 as an key intermediate. In a first step, an anion, 2, is formed via deprotonation with an achiral base this is followed by extraction in the organic phase via formation of a salt complex of type 4 with the phase-transfer organocata-lyst, 3. Subsequently, a nucleophilic substitution reaction furnishes the optically active alkylated products of type 6, with recovery of the catalyst 3. An overview of this reaction concept is given in Scheme 3.1 [1],... 

The first example of a catalytic asymmetric Horner-Wadsworth-Emmons reaction was recently reported by Arai et al. [78]. It is based on the use of a chiral quaternary ammonium salt as a phase-transfer catalyst, 78, derived from cinchonine. Catalytic amounts (20 mol%) of organocatalyst 78 were initially used in the Homer-Wadsworth-Emmons reaction of ketone 75a with a variety of phospho-nates as a model reaction. The condensation products of type 77 were obtained in widely varying yields (from 15 to 89%) and the enantioselectivity of the product was low to moderate (< 43%). Although yields were usually low for methyl and ethyl phosphonates the best enantioselectivity was observed for these substrates (43 and 38% ee, respectively). In contrast higher yields were obtained with phosphonates with sterically more demanding ester groups, e.g. tert-butyl, but ee values were much lower. An overview of this reaction and the effect of the ester functionality is given in Scheme 13.40. 

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