The Tandem Cope-Type Hydroamination/[2,3]-Rearrangement Sequence: A Strategy to Favor the Formation of Intermolecular Hydroamination Products and Enable Difficult Cyclizations

Abstract

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.

Theoretical study on the mechanism of the reaction for alkene hydroaminations catalyzed by chiral aldehyde

“…The first step is 1,2‐addition of 2 on IM0 forming a mixed aminal. Step two is intramolecular hydroamination or named Cope‐type hydroamination, and similar reactions have been studied by several groups . In the following analysis, four pathways are denoted as “Si‐2a,” “Si‐2b,” “Re‐2a,” and “Re‐2b”.…”

Second-order NMR spectra at high field of common organic functional groups

“…Since the triphenyl phosphonium group is extremely large, it seemed a likely candidate to give rise to strong secondorder spectra. n-Propyl triphenylphosphonium bromide 7 was prepared by a literature procedure, 45 and the methylene multiplet next to the phosphorus is displayed in Fig. 8 along with simulated spectra with and without phosphorus coupling.…”

Erratum: Acute toxicity of emamectin benzoate and its desmethyl metabolite to Eohaustorius estuarius

“…Hydroamination reactions of alkynes often resulted in the formation of unstable intermediates like enamines and imines and hence were reduced to the corresponding amines in a one‐pot procedure 7. Hydroaminations were also combined in a tandem process with several other reactions like Cope rearrangement,8 hydroarylation,9 hydrosilylation10 and with diverse addition reactions 11. We are interested in a combination of hydroamination and alkyne addition in a catalytic domino process yielding propargylamines.…”