Concerted conjugate addition of nucleophiles to alkenoates. Part I: Mechanism of N-alkylhydroxylamine additions

Intermolecular conjugate additions of N-alkylhydroxylamines to alpha,beta-u nsaturated esters (alkenoates) produce beta-hydroxyamino ester intermediate s which cyclize to isoxazolidinones. The mechanism of the addition step was investigated by using deuterated starting materials. A five-atom-centered transition state was proposed to explain the stereoselective incorporation of deuterium atoms into the resulting isoxazolidinones. This "concerted" me chanism was further supported by the fact that hydroxylamines could add to trisubstituted alkenoates, resulting in the stereospecific synthesis of 3,4 -dialkyl 5-isoxazolidinones. The use of sterically hindered alkenoates can produce conjugate addition products which are rarely obtained from the inte rmolecular conjugate additions of other nucleophiles. The stereochemistry o f both alpha and beta centers can be controlled to give a high level of sel ectivity even though simple substrates are used.