Does a Concerted Non‐Insertive Mechanism Prevail over a σ‐Insertive Mechanism in Catalytic Cyclohydroamination by Magnesium Tris(oxazolinyl)phenylborate Compounds? A Computational Study

Abstract

The present study comprehensively explores alternative mechanistic pathways for intramolecular hydroamination of 2,2-dimethyl-4-penten-1-amine (1) by [{To(M)}MgMe] (To(M)=tris(4,4-dimethyl-2-oxazolinyl)phenylborate) (2) with the aid of density functional theory (DFT) calculations. A single-step amidoalkene → cycloamine conversion through a concerted proton transfer associated with N-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-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 [{To(M)}Mg-NHR] catalyst. The operative mechanism involves rapid equilibria of the {To(M)}Mg-amidoalkene resting state 3 with its amine adduct, easily accessible and thermodynamically disfavoured, hence reversible, 1,2-olefin insertion into the Mg-N amido σ-bond with ring closure at 3, linked to turnover-limiting Mg-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.

Highly Fluorinated Tris(indazolyl)borate Silylamido Complexes of the Heavier Alkaline Earth Metals: Synthesis, Characterization, and Efficient Catalytic Intramolecular Hydroamination

“…[72] This rate law is consistent with a mechanism implying a fast s-insertive pathway followed by rate-limiting aminolysis, as recently computed for both intraand intermolecular hydroamination. [73][74][75] Alternatively, it may also be accounted for by the interaction between two substrate molecules and the metal center, with the formation of a six-membered transition state involving concerted ring-closure and proton transfer, as the turnover-limiting step. [71] DFT computations performed on {Cpo…”

“…[73][74][75] The strontium analogue 3 was also evaluated in the intramolecular hydroamination reaction of S, displaying a much lower catalytic activity than its Ca analogue. The reaction with 50 equivalents of the aminoalkene at 25 8C only provided a conversion of 10 % in 7 min.…”

Recent Developments in Homogeneous Organomagnesium Catalysis

“…[9] Scheme5.The Hultzsch chiral catalyst 4 and its performance. [12] Later,T obisch published ac omputational paper, [13] in which he calculated both mechanisms using the system proposed by Sadow.H is very detailed investigations,h owever,l ed To bisch to propose a s-insertion mechanism, in contrast to the findings of Sadow.I nh is seminalp aper,T obisch was able to reconcileb oth the experimentala nd theoretical results. For the [tris(oxazolinyl)borate]magnesiums ystem by Sadow and coworkers, based on mechanistice xperiments, as ubstrate-assisted, concerted,n on-insertive mechanism was proposed, following the right route in Scheme6 with 7 as the key transition state (this type was originally introduced by Marks andc oworkers for the analogous lanthanide-catalyzed hydroaminations).…”

“…In contrast, if complex 10 is applied to the catalytic hydroboration of pyridines, the regioselectivity is not translatedf rom the Scheme7.The Hill catalyst 8 and as elected hydroamination reaction. [17] ChemCatChem 2016, 8, [10][11][12][13][14][15][16][17][18][19][20] www.chemcatchem.org stoichiometric reaction. [15] Scheme9.Proposed catalytic cycle for the magnesium-catalyzedhydroboration of pyridines.…”

Hydrophosphination of Styrene and Polymerization of Vinylpyridine: A Computational Investigation of Calcium-Catalyzed Reactions and the Role of Fluxional Noncovalent Interactions

“…Crucially, we provide a deeper level of understanding for each of the steps involved in the reaction pathways. While a number of DFT studies complementing experimental research related to Ae-catalysed hydroamination reactions have been conducted, [24][25][26][27] to the best of our knowledge, this is the first example of a theoretical evaluation of Ae-catalysed hydrophosphination of vinylarenes.…”