The chiral, non-racemic title acids are converted to methyl dioxolane-(cJ 13), oxazoline-(4) and oxazolidinecarboxyiates (cf 9). Deprotonation by Li(i-Pr),N at dry-ice temperature gives solutions of the lithium enolates A-D with exocyclic enolate double bonds. These are stable enough with respect to 8-elimination (Scheme I ) to be alkylated with or without cosolvents such as HMPA or DMPU. The products are formed in good to excellent yields and, with the exception of the tartrate-derived acetonide (see Scheme 2), with diastereoselectivities above 90%. While the tartrate-and threonine-derived enolates (A and B, resp.) are chiral due to the second stereogenic center of the precursors, the serine-and glyceric-acid-derived enolates are non-racemic due to a ferr butyl-suhstituted (pivalaldehyde-derived) acetal center (C and D, resp.). The products of alkylation can be hydrolyzed to give a-branched tartaric acid (Schewze 2), allothreonine (Scheme 3 ) , serine (Scheme 4 ) , and glyceric-acid derivatives (Scheme 5 ) with quaternary stereogenic centers. The configurations of the products are determined by NOE-NMR measurements and by chemical correlation. These show that the dioxolane-derived enolates A and D are alkylated preferentially from that face of the ring which is already substituted ('8yn'-attack), while the dihydrooxazol-and oxazolidine-derived enolates B and C are alkylated from the opposite face ('unfi'-attack). The 'syn'-attack is postulated to arise from strong folding of the heterocyclic ring due to electronic repulsion between the enolate n-system and non-bonding electron pairs on the heteroatoms (see Scheme 5).A) Einleitung. -Enolate mit Abgangsgruppen in y-Stellung zum 0-Atom, also in Allyl-Position zur Enolat-Doppelbindung, sind gewohnlich nicht stabil, es tritt Elimination unter Bildung eines a,P -ungesattigten Carbonyl-Derivates ein (vgl. Aldol-+Enon). Man kann verschiedene Effekte nutzen, um diese Elimination zu unterdriicked), z.

Synthesis of Enantiornerically Pure, a-Alkylated Lysine, Ornithine, and Tryptophan DerivativesThe imidazolidinones 9 and 10 as well as the oxazolidinone 18a were prepared in several steps by known methods from lysine and ornithine with an overall yield of cu. 20%. After double deprotonation with LDA, the corresponding dianionic derivatives could be diastereoselectively alkylated with electrophiles (MeI, C,H,CH,Br, C,H,CHO, CH,CHO). Acid hydrolysis led to the two enantiomeric 2-methyl-and 2-benzyllysines and to the enzyme inhibitor (S)-2-methylornithine. Several a-alkylated tryptophan derivatives were obtained through alkylation of the heterocycles derived from various amino acids with l-(tert-butyloxycarbonyl)-3-(bromomethyl)indole (26). Alkaline hydrolysis of the five-membered auxiliary ring of 30b followed by treatment with HCI afforded (S)-2-methyltryptophan (31

101ChemInform Abstract Deprotonation of the heterocycles (I) (accessible from tartaric acid), (VIII) or (XII) (both available from threonine), (XVIII) (obtained by formylation of a mixture of the serine-derived compounds (XV) and (XVI)), or (XXI) (from serine via glyceric acid) gives solutions of the respective lithium enolates, e.g. (III), with exocyclic enolate double bonds. These are stable enough with respect to β-elimination to be alkylated with various reagents such as (II), (IX), or (XXII) with or without cosolvents such as HMPA. While the tartrate-and threonine-derived enolates (type (III)) are non-racemic due to the second stereogenic center of the precursors, the serine-and glyceric-acid-derived enolates are non-racemic due to a tert.-butyl-substituted (pivalaldehyde-derived) acetal center. The products of alkylation (IV) + (V), (X), (XIII), (XIX), (XXIII) can be hydrolyzed to give the compounds (VI) + (VII), (XI), (XIV), (XX), or (XXIV) with quaternary stereogenic centers. The stereochemical outcome of these reactions and the mechanistic factors involved are discussed in detail.

The imidazolidones (V) (accessible from lysine (Ia) or ornithine by known methods) can be diastereoselectively alkylated with the electrophiles (III), (VIII), or (IX) to give the products (IV), (VI), or (VII) depending on the reaction conditions.

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