Carboxy‐ and Cyano‐Hydroxylation of Alkenes. Synthesis of 3‐Hydroxy‐4‐amino Acids and Butyrolactones via the Isoxazoline Route

Abstract Dichloro‐ and dibromoformaldoximes are useful 1,3‐dipolar cycloaddition reagents. They are conveniently preparated in situ, in high yields by dihalogenation of glyoxalic acid aldoxime with N ‐bromo‐ and N ‐chlorosuccinimide or tert ‐butyl hypochlorite. Dehydrohalogenation with potassium hydrogen carbonate in the presence of alkenes gives 3‐halo‐isoxazolines in a one‐pot reaction. Reduction with iron pentacarbonyl gives β‐hydroxynitriles. Methoxylation and catalytic reduction give β‐hydroxy esters. Allyl alcohols and allylamines are transformed with halonitrile oxides into butyrolactones ( DL ‐angelica lactone) and DL ‐3‐hydroxy‐4‐amino acids (carnitine, 4‐amino‐3‐hydroxybutyric acid), respectively. The lactonization is best effected by heating the γ‐silyloxy ester in acetic acid with potassium hydrogen sulfate as catalyst. A synthesis of N ‐Boc‐dihydromuscimol is described.