Influence of Hydroxylamine Conformation on Stereocontrol inPd-Catalyzed Isoxazolidine-Forming Reactions

摘要

Palladium-catalyzed carboamination reactions between N-Boc-O-(but-3-enyl)hydroxylamine derivativesand aryl or alkenyl bromides afford cis-3,5- and trans-4,5-disubstituted isoxazolidines in good yield withup to >20:1 dr. The diastereoselectivity observed in the formation of cis-3,5-disubstituted isoxazolidinesis superior to selectivities typically obtained in other transformations, such as 1,3-dipolar cycloadditionreactions, that provide these products. In addition, the stereocontrol in the C-N bond-forming Pd-catalyzedcarboamination reactions of N-Boc-O-(but-3-enyl)hydroxylamines is significantly higher than that of relatedC-0 bond-forming carboetherification reactions of N-benzyl-N-(but-3-enyl)hydroxylamine derivatives.This is likely due to a stereoelectronic preference for cyclization via transition states in which the Bocgroup is placed in a perpendicular orientation relative to the plane of the developing ring, which derivesfrom the conformational equilibria of substituted hydroxylamines.