Computational Mechanistic Elucidation of the Intramolecular Aminoalkene Hydroamination Catalysed by Iminoanilide Alkaline-Earth Compounds

• Published in: Chemistry : a European journal 2015-04, Vol.21 (18), p.6765-6779
• Main Author: Tobisch, Sven
• Format: Article
• Language: English
• Subjects: alkaline-earth metals; Alkenes - chemistry; Amination; Amines - chemistry; Anilides - chemistry; Bonding; Catalysis; Catalysts; Chemistry; Closures; Computation; Cyclization; density functional calculations; Earth; homogeneous catalysis; hydroamination; Hydroxyapatite; Imines - chemistry; Metals, Alkaline Earth - chemistry; Models, Theoretical; Olefins; Organometallic Compounds - chemistry; Pathways; reaction mechanisms
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201500233

A comprehensive computational exploration of plausible alternative mechanistic pathways for the intramolecular hydroamination (HA) of aminoalkenes by a recently reported class of kinetically stabilised iminoanilide alkaline‐earth silylamido compounds [{N^N}Ae{N(SiMe3)2}⋅(thf)n] ({N^N}=iminoanilide; Ae=Ca, Sr, Ba) is presented. On the one hand, a proton‐assisted concerted NC/CH bond‐forming pathway to afford the cycloamine in a single step can be invoked and on the other hand, a stepwise σ‐insertive pathway that involves a fast, reversible migratory olefin 1,2‐insertion step linked to a less rapid, irreversible metalC azacycle tether σ‐bond aminolysis. Notably, these alternative mechanistic avenues are equally consistent with reported key experimental features. The present study, which employs a thoroughly benchmarked and reliable DFT methodology, supports the prevailing mechanism to be a stepwise σ‐insertive pathway that sees an initial conversion of the {N^N}Ae silylamido into the catalytically competent {N^N}Ae amidoalkene compound and involves thereafter facile and reversible insertive NC bond‐forming ring closure, linked to irreversible intramolecular AeC tether σ‐bond aminolysis at the transient {N^N}Ae alkyl intermediate. Turnover‐limiting protonolysis accounts for the substantial primary kinetic isotope effect observed; its DFT‐derived barrier satisfactorily matches the empirically determined Eyring parameter and predicts the decrease in rate observed across the series Ca>Sr>Ba correctly. Non‐competitive kinetic demands militate against the operation of the concerted proton‐assisted pathway, which describes NC bond‐forming ring closure triggered by concomitant amino proton delivery at the CC linkage evolving through a multi‐centre TS structure. Valuable insights into the catalytic structure–activity relationships are unveiled by a detailed comparison of [{N^N}Ae(NHR)] catalysts. Moreover, the intriguingly opposite trends in reactivity observed in intramolecular (Ca>Sr>Ba) and intermolecular (Ca