Chirality transfer chelated-enforced

The asymmetric alkylation of a carbonyl group is one of the most commonly used chirality transfer reactions. The chirality of a substrate can be transferred to the newly formed asymmetric carbon atom through this process. In surveying chiral enolate systems as a class of nucleophile, three general subdivisions can be made in such asymmetric nucleophilic addition reactions intra-annular, extra-annular, and chelation enforced intra-annular. 

Chelation-Enforced Intra-annular Chirality Transfer... 

Scheme 2-11. Chelation-enforced intra-annular chirality transfer.

Prolinol-Type Chiral Auxiliaries. In this section, applications of chelation-enforced chirality transfers with nitrogen derivatives are discussed... 

The previous section discussed chelation enforced intra-annular chirality transfer in the asymmetric synthesis of substituted carbonyl compounds. These compounds can be used as building blocks in the asymmetric synthesis of important chiral ligands or biologically active natural compounds. Asymmetric synthesis of chiral quaternary carbon centers has been of significant interest because several types of natural products with bioactivity possess a quaternary stereocenter, so the synthesis of such compounds raises the challenge of enantiomer construction. This applies especially to the asymmetric synthesis of amino group-substituted carboxylic acids with quaternary chiral centers. 

Hereinafter, the extra- and intra- annular chirality transfer (CT) classification defined by Evans402 will be employed provided the original stereocenter is linked to the enol moiety by one or two points of anchorage, with the possibility of chelate-enforced chirality transfer due to internal chelation with heteroatoms (Figure 4)410. 

FIGURE 4. Intra-, extra-annular and chelate-enforced chirality transfer (CT the symbol 9 represents the chiral information)410... 

In recent years, investigations of the diastereoselectivity and enantioselectivity of alkylations of metal enolates of carboxylic acid derivatives have become one of the most active areas of research in synthetic organic chemistry. Intraannular, extraannular and chelate-enforced intraannular chirality transfer may be involved in determining the stereochemistry of these alkylations. 

Extraannular and chelate-enforced intraannular chirality transfer in enolate alkylations of carboxylic acid derivatives may occur in cases where (i) the chiral center, e.g. a 3-carbon atom, is present and remains in the carboxylic portion of the molecule or (ii) the substrate contains a chiral auxiliary, e.g. the alcohol portion of an ester or the amine portion of an amide, which is removed after the alkylation to generate a chiral carboxylic acid. Alkylations of the former type will be discussed in this section. Alkylations of systems containing chiral auxiliaries are described in Section 1.1.6.4. 

Alkylations of acyclic enolates containing a collection of chiral auxiliary groups have been used successfully for the asymmetric synthesis of carboxylic acids. The chiral, nonracemic substrates that have been used include amides, imides, esters, imine derivatives of glycinates and acyl derivatives of chiral transition metals. In these systems either extraannular or chelate-enforced intraannular chirality transfer may control the sense of the alkylation step. 

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