Stereoselective synthesis of β-substituted-l-threonines from enantiopure 5-acetyl-2-isoxazolines

Enantiomerically pure, 3-methyl- or 3-ethoxycarbonyl-substituted (5S)- and (5R)-5-acetyl-2-isoxazolines were obtained from the corresponding racemic mixtures by means of an enzymatic reduction with baker’s yeast, followed by the separation of the enantiopure syn- and anti-alcohols and oxidation of the alcohol group. The reaction between these ketones and (2R)-Schöllkopf’s bislactim ether azaenolate was studied: using (5S)- and (5R)-3-methyl derivatives, two diastereoisomeric adducts were obtained in good yield and stereoselectivity, whereas reaction with the (5S)- and (5R)-3-ethoxycarbonyl derivatives led to a complex mixture of products. Subsequent controlled hydrolysis of the pyrazine ring led to β-(3-methyl-4,5-dihydro-isoxazol-5-yl)-l-threonines methyl ester together with the corresponding (R)-valine dipeptides.