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Keywords:

  • alkaline-earth metals;
  • density functional calculations;
  • hydroamination;
  • magnesium;
  • reaction mechanisms

Abstract

The present study comprehensively explores alternative mechanistic pathways for intramolecular hydroamination of 2,2-dimethyl-4-penten-1-amine (1) by [{ToM}MgMe] (ToM=tris(4,4-dimethyl-2-oxazolinyl)phenylborate) (2) with the aid of density functional theory (DFT) calculations. A single-step amidoalkene [RIGHTWARDS ARROW] cycloamine conversion through a concerted proton transfer associated with N[BOND]C ring closure has been explored as one possible mechanism; its key features have been described. This non-insertive pathway evolves via a six-centre TS structure featuring activation of the olefin unit towards nucleophilic amido attack outside the immediate vicinity of the metal centre by amino proton delivery and describes a viable mechanistic variant for alkaline-earth metal-mediated aminoalkene hydroamination. However, herein is presented sound evidence for the operation of the Mg[BOND]N amido σ-bond insertive mechanism, its turnover-limiting activation barrier is found to be 5.0 kcal mol−1 lower than for the non-insertive mechanism, for the cyclohydroamination of 2,2-disubstituted 4-aminoalkenes by a [{ToM}Mg[BOND]NHR] catalyst. The operative mechanism involves rapid equilibria of the {ToM}Mg[BOND]amidoalkene resting state 3 with its amine adduct, easily accessible and thermodynamically disfavoured, hence reversible, 1,2-olefin insertion into the Mg[BOND]N amido σ-bond with ring closure at 3, linked to turnover-limiting Mg[BOND]C azacycle tether aminolysis by an adduct substrate molecule, followed by facile cycloamine liberation to regenerate the active catalyst species 3. The following aspects are in support of this scenario: 1) the derived rate law is consistent with the experimentally obtained empirical rate law; 2) the reasonable agreement between the computationally estimated and the observed value of the primary KIE; 3) the assessed effective activation barrier for turnover-limiting aminolysis matches empirically determined Eyring parameters remarkably well; and 4) the observed resistance of isolated 3 to undergo amidoalkene cycloamine/cycloamido transformation until further quantities of substrate is added is consistently explained. The herein unveiled insights into the structure–reactivity relationships will undoubtedly govern the rational design of alkaline-earth metal-based catalysts and likely facilitate further advances in the area.