In the same manner that the Nasobem, Stiimpke's mythical creature, teaches his child the peculiar way of life of the species Nasobema lyricum, the work of Seebach et al. on the self-regeneration of stereocenters has been governed by a fanciful idea. On the way, many tricks have been learned and much knowledge gained. Finally, they have come back down to earth and find themselves once again in the unimaginative world of enantiomer separation for the synthesis of enantiomerically pure compounds. In order to replace a substituent at a single stereogenic center of a chiral molecule without racemization, a temporary center of chirality is first generated diastereoselectively, the original tetragonal center is then trigonalized by removal of a substituent, a new ligand is introduced, again diastereoselectively, and finally, the temporary center is removed. By means of these four steps (the "Self-Regeneration of Stereocenters", SRS), 2-and 3-amino-, hydroxy-, and sulfanylcarboxylic acids have been successfully alkylated with formation of tertiary carbon centers and without the use of a chiral auxiliary. Use of this methodology has allowed the potential of these inexpensive chiral building blocks to be expanded considerably. This article aims to demonstrate (using, in part, examples from natural product syntheses) that chiral heterocyclic acetals with enamine, enol ether, enolate, dienolate, enoate, radical, and acyliminium functionalities and also those that are potential reactants for Michael additions and pericyclic processes (for example, electron-rich and electronpoor dienophiles and dienes) are now easily accessible, more often than not, in both enantiomeric forms. Stereogenic nitrogen atoms of aziridines, boron atoms of cyclic or linear systems, and stereogenic planes of x-complexes can also be used as the temporary chirality element in other approaches to the realization of the SRS principle. Enantiomerically pure derivatives of, for example, glycine, hydroxy-and sulfanylacetic acid, 3-aminopropanoic acid, and 3-oxocarboxylic acids can be prepared by resolution of racemic mixtures via diastereoisomeric salts or by chromatography on a chiral column. Hence, the extensive reactivity of compounds developed to test the SRS principle and, above all, the outstanding stereoselectivities of the reactions can be put to good use even when no suitable chiral precursor is availabl-ven though this amounts to an abandonment of the principle! The readily available 2-tertbutyl-l,3-imidazolidin-3-one, -0xazolid-in-5-one, -dioxin-3-one, and -hydropyrimidinone (all of which contain a single stereogenic center at the acetal C atom) can thus be used in the preparation of a vast range of 2-amino-and 3-hydroxycarboxylic acids, and no chiral auxiliary has to be removed or regenerated during these procedures. (One example is the synthesis of 4-fluoro-MeBmt, a derivative of the C, amino acid found in cyclosporin.) In the final chapter we will discuss the most useful findings gained from investigations into both the self-regeneration of ste...
