The tandem hydroamination/Meisenheimer rearrangement sequence was developed to address the issue of unfavorable reaction thermodynamics for intermolecular reactions of alkenes and to improve the scope of Cope-type hydroaminations. This tandem sequence allows intermolecular reactions of N-alkyl-N-methallylhydroxyl-amines to be energetically more favorable: the N-oxide intermediate formed via Cope-type hydroamination, which can revert to the starting materials via a Cope elimination, can form a more stable neutral product via a [2,3]-Meisenheimer rearrangement. This tandem sequence also leads to increased efficiency in intramolecular systems as illustrated by syntheses of two alkaloids (coniine and norreticuline) featuring difficult hydroamination key steps.

Amination O 0268The Tandem Cope-Type Hydroamination/[2,3]-Rearrangement Sequence: A Strategy to Favor the Formation of Intermolecular Hydroamination Products and Enable Difficult Cyclizations. -The process allows intermolecular reactions of N-alkyl-N-methallylhydroxylamines to be energetically more favorable: the N-oxide intermediate formed via Cope-type hydroamination can form a more stable neutral product via a [2,3]-Meisenheimer rearrangement. This tandem sequence also leads to increased efficiency in intramolecular systems as is illustrated by synthesis of the alkaloids N-acetyl coniine (XVII) and norreticuline (XXII). -(BOURGEOIS, J.; DION, I.; CEBROWSKI, P. H.; LOISEAU, F.; BEDARD, A.-C.; BEAUCHEMIN*, A. M.; J. Am. Chem. Soc. 131 (2009) 3, 874-875; Dep. Chem., Univ. Ottawa, Ottawa, Ont. K1N 6N5, Can.; Eng.) -Bartels 22-044

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