Concerted Conjugate Addition of Nucleophiles to Alkenoates. Part I: Mechanism of N-Alkylhydroxylamine Additions

Abstract

Intermolecular conjugate additions of N-alkylhydroxylamines to α,β-unsaturated esters (alkenoates) produce β-hydroxyamino ester intermediates 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” mechanism 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 intermolecular conjugate additions of other nucleophiles. The stereochemistry of both α and β centers can be controlled to give a high level of selectivity even though simple substrates are used.