ISSN:
0170-2041
Keywords:
D- or L-Threonines
;
Aldol additions
;
Diastereoselective coupling of trigonal centers
;
1,3-Oxazolidin-5-ones
;
1,3-Oxazolidin-2-ones, 5-substituted, 4-carboxylic acid
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Lithium enolates of (R)- or (S)-oxazolidinones 1 (specified in the title) are generated with lithium hexamethyldisilazanide (LHMDS) in THF at -75°C and added to aliphatic or aromatic aldehydes (products 2-18 of hydroxyalkylation, yields mostly over 80%, diastereoselectivities usually over 98%; Scheme 2). The adducts can be cleaved to give threonine analogs (19-32) under salt-free conditions (H2/Pd-C, then H2O and evaporation of the solvents, Scheme 3). In some cases, the primary adducts may cyclize with elimination of benzyl alcohol to give bicyclic carbamates 33 which, in turn, can be hydrolyzed to 5-substituted trans-2-oxo-1,3-oxazolidine-4-carboxylic acids 34 (Scheme 4). - The essentially complete threo selectivity of the coupling step is proved by NMR spectroscopy and by chemical correlations. The stereochemical course of the reaction is opposite to that observed with carbocyclic enolates; possible reasons for this behavior are discussed (Scheme 5). - The starting material rac-1, prepared from glycine, pivalaldehyde and benzyl chloroformate, is readily resolved by chromatography on preparative scale by using the stationary phase Chiraspher® and a Prepbar® system (Scheme 1); the undesired enantiomer may be recycled by thermal racemization (heating at reflux in CH3CN for 8 h).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jlac.1991199101184
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