Intra-annular chirality transfer

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. 

The definition of intra-annular chirality transfer can be best established by the following examples (Scheme 2-1)7 ... 

The examples in Scheme 2-1 show that in intra-annular chirality transfer the resident asymmetric center connects to the enolate through annular covalent bonds. The geometric configuration of the enolate can be either immobile or irrelevant to the sense of asymmetric induction. 

Chelation-Enforced Intra-annular Chirality Transfer... 

As a result of the combination of intra- and extra-annular chirality transfer, a productive approach has been developed for the design of chiral enolate systems in which a structurally organized diastereofacial bias is established, as illustrated in the equations in Scheme 2-11. A lithium-coordinated five-membered or six-membered ring fixes the orientation between the inducing asymmetric center and the enolate20 ... 

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

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... 

---