Influence of hydroxylamine conformation on stereocontrol in Pd-catalyzed isoxazolidine-forming reactions.
Palladium-catalyzed carboamination reactions between N-Boc-O-(but-3-enyl)hydroxylamine derivatives and aryl or alkenyl bromides afford cis-3,5- and trans-4,5-disubstituted isoxazolidines in good yield with up to >20:1 dr. The diastereoselectivity observed in the formation of cis-3,5-disubstituted isoxazolidines is superior to selectivities typically obtained in other transformations, such as 1,3-dipolar cycloaddition reactions, that provide these products. In addition, the stereocontrol in the C-N bond-forming Pd-catalyzed carboamination reactions of N-Boc-O-(but-3-enyl)hydroxylamines is significantly higher than that of related C-O 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 Boc group is placed in a perpendicular orientation relative to the plane of the developing ring, which derives from the conformational equilibria of substituted hydroxylamines.
Lemen
Georgia S
GS
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
Giampietro
Natalie C
NC
Hay
Michael B
MB
Wolfe
John P
JP
D000586:Amination; D002384:Catalysis; D003500:Cyclization; D019811:Hydroxylamine / Q000737:chemistry*; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis*; D010165:Palladium; D013237:Stereoisomerism
D010080:Oxazoles; C064210:oxazolidine; D019811:Hydroxylamine; D010165:Palladium