The Cope hydroamination reaction does not require catalyst, proceeds with high stereoselectivity, and is applicable to highly substituted alkenes that are challenging substrates in direct hydroamination (Eq. 23). Synthetic applications of this reaction are limited to monosubstituted hydroxylamines, as disubstituted hydroxylamines react reversibly to afford -oxides. The sensitivity of many hydrazines and hydroxylamines to oxidation also presents a significant limitation.
Mechanisms of hydroaminations catalyzed by late transition metals are not as well understood as the mechanisms discussed above. Nonetheless, it is generally believed that these reactions involve either amine activation via N-H insertion or alkene activation via π-coordination. Intermolecular hydroamination of norbornene catalyzed by an iridium(I) complex provides an example of the former (Eq. 4). Oxidative addition of the amine is followed by insertion of the alkene and reductive elimination.
alkenes reactions and synthesis - [PPT Powerpoint]
In general, hydroaminations present issues of site selectivity (Markovnikov/anti-Markovnikov) and enantioselectivity. Site selectivity is a function of the unsaturated substrate as well as the catalyst. The scope of enantioselective hydroamination is very broad; however, a particular catalyst system is typically limited to a fairly narrow range of substrates.
electrophilic addition mechanism steps addition …
As a consequence of the importance of nitrogen-containing compounds in biological and pharmaceutical applications, methods for the construction of carbon-nitrogen bonds have been heavily studied for at least 150 years. Hydroamination, the addition of HNR2 across a carbon-carbon π bond, is in principle one of the most atom-economical methods for the synthesis of this class of compounds. Catalytic hydroaminations of alkenes, allenes, and dienes (which may be inter- or intramolecular) afford amines, imines, and enamines (Eq. 1).
cis-Alkene synthesis by olefination
The scope of amine substrates includes ammonia, primary and secondary aliphatic and aromatic amines, azoles, hydrazines, and -protected amines. Transition metal, rare earth, and alkali metal catalysts have been applied successfully, although the appropriate choice of catalyst depends on the unsaturated and amine substrates.
Alkene Synthesis & Reactions - [PDF Document]
Mechanisms of alkene hydroaminations depend strongly on the catalyst system employed. Catalysts that include electropositive elements such as alkali, alkaline earth, and rare earth metals typically operate through a metal-amido species that undergoes nucleophilic addition to the alkene (Eq. 2). The site selectivity of this addition depends on the substitution of the alkene: whereas aliphatic alkenes typically undergo Markovnikov addition, aromatic alkenes more commonly engage in anti-Markovnikov addition due to stabilization of the resulting benzylic metal intermediate.
Alkynes: Reactions and Synthesis - Chemgapedia
Hydroaminations of allenes catalyzed by Group 4 metals proceed by a different mechanism involving a metal intermediate (Eq. 3). After formation of a bis-amido precursor, α-elimination generates the metal imido species, which engages in [2+2] cycloaddition with the allene substrate. Protonation then generates an enamido complex with an additional amido ligand; α-elimination then regenerates the metal-imido species.