Chiral skeleton

In contrast to the extensive studies on phosphine-phosphites, the corresponding phosphine-phosphinites are rarely exploited. Laschat introduced this design with a bicydic chiral skeleton derived from (lS)-(+)-camphorsulfonic acid [127]. The Rh-complex based on dimesitylphosphinite 154b was found to be the most reactive catalyst, and was used to produce methyl N-2-acetamidodnnamate, with 89% ee. 

A number of dithioethers 169-173 (Fig. 27.16) based on the chiral skeleton of some well-known phosphines such as DIOP, Deguphos and BINAP, have been reported. The use of 1,4-dithioether ligands which lack contiguous chiral centers such as (+)-DiopsR2 169 [130], BINASR2 172 [131] and 173 [132] in the Ir- or... 

It is evident that the case o = n corresponds to chiral skeletons, which lead to chiral molecules even if all ligands are identical. 

For chiral classes we showed above, under the restriction to achiral ligands, that the chirality order has the lower limit n — 3 and the upper limit n which characterizes chiral skeletons. If chiral ligands are admitted we have the relation o o+ and therefore the same limits for o. 

The dissection of 22 leads on one hand to a chiral skeleton and a set of achiral ligands, and on the other hand to an achiral skeleton and a set of ligands that contains a chiral ligand. 

Amide-linked catenanes and rotaxanes can play a major role in the study of rare forms of chirality, e.g. topological chirality and cycloenantiomerism [60]. Resolution of enantiomeric catenanes, rotaxanes, and pretzelanes has been achieved by HPLC on chiral column materials, but further work must be performed to determine absolute configurations and to realize new chiral skeletons composed of achiral building blocks. Topological asymmetric synthesis still belongs to dreams of the future yet should be kept in mind. 

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. 

The naturally occurring cinchona alkaloids (Figure 8.1), as described in other chapters of this book, have proven to be powerful organocatalysts in most major chemical reactions. They possess diverse chiral skeletons and are easily tunable for diverse catalytic reactions through different mechanisms, which make them privileged organocatalysts. The vast synthetic potential of cinchona alkaloids and their derivatives in the asymmetric nucleophilic addition of prochiral C=0 and C=N bonds has also been well demonstrated over the last decade. 

Remark (The case of a chiral skeleton) If P = R, the skeleton of the molecule is chiral and so the total number of permutational isomers is... 

In addition to the previously discussed diphosphanes, some phosphinite-type ligands are among those that are considered as ligands of the state-of-the-art systems. The naturally abundant mono- and disaccharides provide a chiral skeleton for the facile synthesis of diphosphinites as 2,3-Carbophos and 3,4-Carbophos (34), tris-phosphinite, and glucophinite (35). 

Scheme 1.7 Diastereoselective methylation of 3-hydroxybutanoate 18 - an example of a diastereoselective conversion of a lithium enolate with a chiral skeleton.

However, diastereoselective transformations like this are not to be discussed within this monograph, as they do not fulfill the criteria of asymmetric synthesis, according to Marckwald s definition (in today s language) this would mean [...] those reactions, or sequences of reactions, which produce chiral nonracemic substances from achiral compounds with the intermediate use of chiral nonracemic materials, but excluding a separation operation [35]. Thus, diastereoselective conversions not included for that reason in this book are, for example, aldol additions, Mannich reactions, and Michael additions of enolates to ketones, imines, and cx,P-unsaturated carbonyl compounds, respectively, with any chiral skeleton. For such stereoselective enolate reactions that are not asymmetric syntheses, the reader is referred to the literature, which treated this topic in a comprehensive manner [36]. 

The strength of the Paterson approach is clearly due to the fact that this method is highly efficient for aldol additions of ketones with a chiral skeleton to chiral or achiral aldehydes, in the course of which the diisopinocampheylborane eno-lates exhibit distinct stereocontrol. An illustrative example thereof is shown in Scheme 4.67 by the stereodivergent aldol addition of enantiomerically pure ketone... 

As shown in the next chapters, some of these reactions were also successfully employed to access the chiral skeletons of complex natural products or biologically active molecules. The following chapters will therefore highlight the successful use of the three most prominent chiral ammonium salt PTC classes Cinchona alkaloids, Maruoka s catalysts, and Shibasaki s catalysts) to facilitate demanding stereoselective key steps in complex natural product syntheses and in the synthesis of biologically active (either natural or synthetic) compounds. 

Since 2(X)7, other chiral primary amines such as 35-39 (Fig. 5.1) have been synthesized and explored in the catalysis of asymmetric direct aldol reactions [21-23]. Maruoka developed primary amine catalysts 36 and 37 using a common chiral skeleton. Interestingly, these two catalysts demonstrated opposite chiral... 

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