The tandem Cope-type hydroamination/[2,3]-rearrangement sequence: a strategy to favor the formation of intermolecular hydroamination products and enable difficult cyclizations.
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.
Bourgeois
Joffré
J
Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada, K1N 6N5.
Dion
Isabelle
I
Cebrowski
Pamela H
PH
Loiseau
Francis
F
Bédard
Anne-Catherine
AC
Beauchemin
André M
AM
D000586:Amination; D000588:Amines / Q000737:chemistry*; D003500:Cyclization; D006859:Hydrogen / Q000737:chemistry*; D006865:Hydrogenation; D015394:Molecular Structure
D000588:Amines; D006859:Hydrogen