Experimental and Computational Mechanistic Studies of the β‐Diketiminatoiron(II)‐Catalysed Hydroamination of Primary Aminoalkenes

Abstract

A comprehensive mechanistic study by means of complementary experimental and computational approaches of the exo‐cyclohydroamination of primary aminoalkenes mediated by the recently reported β‐diketiminatoiron(II) complex B is presented. Kinetic analysis of the cyclisation of 2,2‐diphenylpent‐4‐en‐1‐amine (1 a) catalysed by B revealed a first‐order dependence of the rate on both aminoalkene and catalyst concentrations and a primary kinetic isotope effect (KIE) (kH/kD) of 2.7 (90 °C). Eyring analysis afforded ΔH≠=22.2 kcal mol−1, ΔS≠=−13.4 cal mol−1 K−1. Plausible mechanistic pathways for competitive avenues of direct intramolecular hydroamination and oxidative amination have been scrutinised computationally. A kinetically challenging proton‐assisted concerted N−C/C−H bond‐forming non‐insertive pathway is seen not to be accessible in the presence of a distinctly faster σ‐insertive pathway. This operative pathway involves 1) rapid and reversible syn‐migratory 1,2‐insertion of the alkene into the Fe−Namido σ bond at the monomer {N^N}FeII amido compound; 2) turnover‐limiting Fe−C σ bond aminolysis at the thus generated transient {N^N}FeII alkyl intermediate and 3) regeneration of the catalytically competent {N^N}FeII amido complex, which favours its dimer, likely representing the catalyst resting state, through rapid cycloamine displacement by substrate. The collectively derived mechanistic picture is consonant with all empirical data obtained from stoichiometric, catalytic and kinetics experiments.

Alkene Hydroamination via Earth‐Abundant Transition Metal (Iron, Cobalt, Copper and Zinc) Catalysis: A Mechanistic Overview

“…The formation of iron amido complexes I ( I _Me and I _Ph), isolated and characterized as centrosymmetric amido‐bridged dimers [ I ] 2 , advocate the amine deprotonation pathway by the alkyl catalyst (Scheme , bottom and Scheme ). Additionally, the formation of insertive products from direct reactivity of isolated dimer [ I _Ph] 2 without the assistance of an additional proton source and the syn ‐stereochemistry of the cyclization are in favor of a C−N bond formation proceeding by alkene migratory 1,2‐insertion via a stepwise σ‐insertive mechanism . This insertive‐type mechanism has been previously proposed for hydroamination reactions catalyzed by rare earth and alkaline metal complexes .…”

“…The catalytic efficiency of complex [ I _Ph] 2 was similar to that of complex 2a‐Fe suggesting the participation of the latter in the catalytic cycle . The detailed computational survey of the conceivable mechanistic avenues for the hydroamination pathway suggests that an alternative concerted pathway is less favored in the presence of a more kinetically accessible σ‐insertive mechanism . This concerted pathway evolving concomitant C−N/C−H bond formation via a multi‐center transition state structure, was put forward as a distinct operating hydroamination mechanism for some rare earth‐, alkaline‐ and Group 4 metal‐based catalysts…”

“…However, this selectivity enrichment was achieved at the expense of the reaction rate. More recently, a combined experimental and computational mechanistic study of this transformation promoted by catalyst 2a‐Fe (without cyclopentylamine) was undertaken . Kinetic analysis of the cyclohydroamination reaction of 2,2‐diphenylpent‐4‐en‐1‐amine provides the empirical second‐order rate law v=k[ 2a‐Fe ] 1 [aminoalkene] 1 , a primary KIE ( k H / k D ) of 2.7 (90 °C) and the activation entropy value of Δ S ≠ =−13.4 cal mol −1 K −1 .…”

“…Kinetic analysis of the cyclohydroamination reaction of 2,2‐diphenylpent‐4‐en‐1‐amine provides the empirical second‐order rate law v=k[ 2a‐Fe ] 1 [aminoalkene] 1 , a primary KIE ( k H / k D ) of 2.7 (90 °C) and the activation entropy value of Δ S ≠ =−13.4 cal mol −1 K −1 . These data suggest a higher‐order transition state associated with the turnover‐limiting step of the catalytic cycle involving the participation of a single adducted aminoalkene and the breaking of an N−H bond . The formation of iron amido complexes I ( I _Me and I _Ph), isolated and characterized as centrosymmetric amido‐bridged dimers [ I ] 2 , advocate the amine deprotonation pathway by the alkyl catalyst (Scheme , bottom and Scheme ).…”

“…On the basis of these accumulated experimental and computational data, a stepwise σ‐insertive mechanism is proposed by the authors as the operating mechanism for the cyclohydroamination reaction catalyzed by 2a‐Fe (without cyclopentylamine) as displayed in Scheme ( bottom ) for substrate 1b . Initial σ‐bond metathesis between 2a‐Fe and aminoalkene 1b delivers the catalytically relevant monomeric species I _Me, which is in equilibium with its amido dimer [ I _Me] 2 being likely the catalyst resting state.…”