Alkylation studies of 5-exo-methylene substituted isoxazolidines

Abstract

1,3-bipolar cycloaddition of nitrones to phenylsulphonylallene gives in high yield and with complete regiospecificity 5-methyleneisoxazolidines. These on treatment with base and subsequent reaction with electrophiles afford both α- and γ-substituted products. With methyl iodide as the electrophile, only the α-methylated product was isolated. In contrast, reaction of the 5-exo-methylene-4-phenylsulphonylisoxazolidine with allyl bromide afforded the γ-allylated product. Formation of this was shown to be via direct γ-attack, rather than by α-attack, followed by a 3,3-sigmatropic rearrangement. Further studies show that the product ratio is controlled by a sensitive interplay between thermodynamic and steric factors and is very dependent on the nature of the electrophile used.