Stereoselective Electrophilic Cyclisation of O-Homoallyl Hydroxylamine Derivatives­

Abstract

Electrophilic cyclisations of various O-homoallyl hydroxylamine derivatives are discussed. Non-protected O-homoallyl hydroxylamines undergo oxidative cyclisations to isoxazolines. The new isoxazoline synthesis comprises an initial electrophilic cyclisation to form intermediate isoxazolidines, which are subsequently oxidized to isoxazolines. Cyclisations can be conducted with various electrophiles (t-BuOCl, PhSeBr, NBS and NIS). Oxidation can be suppressed if the starting O-homoallyl hydroxylamines are N-sulfonylated. The electrophilic cyclisation then provides N-sulfonylated isoxazolidines with moderate cis-selectivity (up to 7:1). Electrophilic cyclisation of N-acylated O-homoallyl hydroxylamines provides isoxazolines or isoxazolidines depending on the reaction conditions (reagents). The t-BuOCl-mediated cyclisation affords isoxazolines via an oxidative cyclisation, whereas the NIS-induced reaction provides the 5-exo-cyclisation product with high stereoselectivity (cis:trans = 13:1).

Key words

stereoselective synthesis - electrophilic additions - isoxazolidines - isoxazolines - oxidative cyclisations

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9

Janza, B. unpublished results.

10

To the best of our knowledge, there is only one report describing the electrophilic cyclisation of homoallyloxyamines, see Ref. [8b]

12

Similar electrophilic cyclisation/oxidation reactions have been observed in Se-induced 5-endo-type cyclisations of hydrazines, see Ref. [4b]

18

All the cyclisations were performed using racemic olefins. In the schemes only one enantiomer is shown.