Stereoselective Alkylierung an C(α) von Serin, Gycerinsaeure, Thereonin und Weinsaeure ueber heterocyclische Enolate mit exocyclischer Doppelbindung

Article abstract of DOI:10.1002/hlca.19870700426

The chiral, non-racemic title acids are converted to methyl dioxalene- (cf. 13), oxazoline- (4) and oxazolidine-carboxylates (cf. 9).Deprotonation by Li(i-Pr)2N at dry-ice temperature gives solutions of the litium enolates A-D with exocyclic enolate double bonds.These are stable enough with respect to β-elimination (Scheme 1) 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 Schemem 2), with diastereoselectivities above 90percent.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 tert butyl-substituted (pivalaldehyde-derived) acetal center (C and D, resp.).The products of alkylation can be hydrolyzed to give α-branched tartaric acid (Scheme 2), allothreonine (Scheme 3), serine (Scheme 4), and glycerine-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 taht the dioxolane-derived enolates A and D are alkylated preferentially from that face of the ring which is alredy substituted ('syn'-attack).The 'syn'-attack is postulated to arise from strong folding of the heterocyclic ring due to elelctronic repulsion between the enolate ?-system and non-bonding elelctron pairs on the heteroatoms (see Scheme 6).