Cinchona chirality inducers

As mentioned in the previous section, nowadays, readily available and inexpensive cinchona alkaloids with pseudoenantiomeric forms, such as quinine and quinidine or cinchonine and cinchonidine, are among the most privileged chirality inducers in the area of asymmetric catalysis. The key feature responsible for their successful utility in catalysis is that they possess diverse chiral skeletons and are easily tunable for diverse types of reactions (Figure 1.2). The presence of the 1,2-aminoalcohol subunit containing the highly basic and bulky quinuclidine, which complements the proximal Lewis acidic hydroxyl function, is primarily responsible for their catalytic activity. 

Cinchona alkaloids have characteristic structural features for their diverse conformations and self-association phenomena. Therefore, knowledge of their real structure in solution can provide original information on the chiral inducing and discriminating ability of these alkaloids. 

Cinchona Alkaloid Derivatives as Chirality Inducers in Metal-Catalyzed Reactions... 

Cinchona Alkaloids and their Derivatives as Chirality Inducers in Metal-Promoted Enantioselective Carbon-Carbon and Carbon-Heteroatom Bond Forming Reactions... 

This chapter has presented the current stage in the development of metal-promoted asymmetric C—C and C—X bond forming reactions, in which cinchona alkaloids are utilized as chirality inducers. As shown in many of the examples discussed above, cinchona alkaloids and their derivatives have great potential to serve as chiral ligands or cobase catalysts in diverse metal-promoted asymmetric C—C and C—X bond forming reactions. However, despite the scientific achievements that have been made... 

The appendix lists selected examples of cinchona-promoted asymmetric reactions. The table is organized according to the reaction types. Detailed information on the reaction procedures and the availability of cinchona-based chiral inducers is found in the corresponding chapter(s) and reference(s). 

This multiauthor handbook will cover the whole spectrum of cinchona alkaloid chemistry ranging from the fundamentals to industrial applications. This book is organized in four units, namely, the use of cinchona alkaloids as chirality inducers in metal-promoted reactions (Chapters 2-4), the use of cinchona alkaloids as chiral organocatalysts (Chapters 5-11), the organic chemistry of cinchona alkaloids themselves (Chapter 12), and the use of cinchona alkaloids as chiral discriminating agents... 

Abid, M. and Torok, B., Cinchona alkaloid induced chiral discrimination for the determination of the enantiomeric composition of a-trifluoro-methylated-hydroxyl compounds by NMR spectroscopy. Tetrahedron Asymm., 16,1547,... 

An attractive alternative to these novel aminoalcohol type modifiers is the use of 1-(1-naphthyl)ethylamine (NEA, Fig. 5) and derivatives thereof as chiral modifiers [45-47]. Trace quantities of (R)- or (S)-l-(l-naphthyl)ethylamine induce up to 82% ee in the hydrogenation of ethyl pyruvate over Pt/alumina. Note that naphthylethylamine is only a precursor of the actual modifier, which is formed in situ by reductive alkylation of NEA with the reactant ethyl pyruvate. This transformation (Fig. 5), which proceeds via imine formation and subsequent reduction of the C=N bond, is highly diastereoselective (d.e. >95%). Reductive alkylation of NEA with different aldehydes or ketones provides easy access to a variety of related modifiers [47]. The enantioselection occurring with the modifiers derived from NEA could be rationalized with the same strategy of molecular modelling as demonstrated for the Pt-cinchona system. 

The notable mode of stereoselectivity of Cinchona alkaloids is presented by its psendoenantiomeric pairs which can be employed to generate either enantiomer of chiral prodnct. Key moieties that are central to Cinchona alkaloids are the quinuclidine nitrogen and the adjacent C(9)-OH (the N-C(8)-C(9)-OH moiety) (Fig. 2). In psendoentiomeric alkaloids in the natural open conformation, the torsion angle N-C(8)-C(9)-0 are opposite in sign Q and CD are (-), and thereby induce selectivity for one enantiomer, whereas QD and C are (-I-) and afford the other enantiomer [28, 29],... 

The efficiency with which modified Cinchona alkaloids catalyze conjugate additions of a-substituted a-cyanoacetates highlights the nitrile group s stereoselective role with the catalyst. Deng et al. [60] utilized this observation to develop a one-step construction of chiral acyclic adducts that have non-adjacent, 1,3-tertiary-quatemary stereocenters. Based on their mechanistic studies and proposed transition state model, the bifimctional nature of the quinoline C(6 )-OH Cinchona alkaloids could induce a tandem conjugate addition-protonation reaction to create the tertiary and quaternary stereocenters in an enantioselective and diastereoselective manner (Scheme 18). 

Chiral phase transfer catalysts have been exploited in a wide range of reactions which involve anionic intermediates. Remarkably, quaternary ammonium salts of 1 and 2 have been shown to induce asymmetry in many different synthetic reactions, and the cinchona alkaloids appear to be a charmed template for the design of effective phase transfer catalysts [14],... 

Reagent-Induced Enantioface Differentiating Osmylations 4.4.4.1. Chiral Ligands for Catalytic Osmylations 4.4.4.I.I. Cinchona Alkaloid Derivatives as Chiral Ligands... 

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