Bromocyclization of Unsaturated Oximes. Synthesis of Five-Membered Cyclic Nitrones (Pyrroline N-Oxides)

Abstract

The cyclization of a ribose-derived pentenose oxime with various halogen electrophiles showed bromine to be the most effective reagent, leading to 80% of L-lyxo/D-ribo-pyrroline N-oxides in an 84:16 diastereomeric ratio. In order to explore the scope of this facile process, several other γ,δ - unsaturated oximes were submitted to this reaction. Depending on the substitution pattern, 23 - 87%, yields of pyrroline N-oxides of were registered. With α-allyl-β -ketoester oximes the alkoxycarbonyl group proved a similar (ethoxy) or even better (t-butoxy) trapping nucleophile, leading preferentially to the corresponding bromolactone oxime. - With 2,2-dimethyl-3-butene aldoxime, the corresponding 3-bromopyrroline N-oxide was formed, due to a formal, unusual N-endo cyclization to the chain terminus. This was exploited for a new access to six-membered nitrones from a γ,δ -pentene aldoxime, with addition of Br/OH to the C=C of the 4-pentenal first, and oximation/cyclization following then

Crystal structure of (2RS)-2-bromomethyl-4,4-dimethyl-3,4-dihydro- 2H-pyrrole 1-oxide hemi(hydrobromide), C7H12BrNO · ½HBr

“…The title compound has been obtained by bromocyclization of 2,2-dimethyl-4-pentenal oxime [1][2][3][4][5][6][7]. The crystallization of the product from dichloromethane furnished the title nitrone in the form of colorless crystals (m.p.…”

Crystal structure of rel-(2R,3S)-2-bromomethyl-3-phenyl-3,4-dihydro- 2H-pyrrole 1-oxide, C11H12BrNO

“…The title compound has been obtained by bromocyclization of 3-phenyl-4-pentenal oxime [1][2][3][4][5][6][7]. The two diastereoisomers (ratio 40:60) were separated by column chromatography (ethyl acetate/methanol), whereby crystallization of the major isomer from dichloromethane furnished the title nitrone in the form of colorless crystals (m.p.…”

Crystal structure of rel-(2R,3S)-2-bromomethyl-3-phenyl-3,4-dihydro- 2H-pyrrole 1-oxide, C11H12BrNO

“…The title compound has been obtained by bromocyclization of 3-phenyl-4-pentenal oxime [1][2][3][4][5][6][7]. The two diastereoisomers (ratio 40:60) were separated by column chromatography (ethyl ace- (2) …”