Letter Cite This: ACS Catal. 2019, 9, 6080−6086
pubs.acs.org/acscatalysis
Generation of Carbon Radical from Iron-Hydride/Alkene: ExchangeEnhanced Reactivity Selects the Reactive Spin State Hao Jiang,†,‡ Wenzhen Lai,‡ and Hui Chen*,† †
Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Photochemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China ‡ Department of Chemistry, Renmin University of China, Beijing 100872, P. R. China
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ABSTRACT: Iron-hydride and alkene constitute a promising pair of reactants to access alkyl carbon radicals. However, the fundamental mechanistic scenario remains unclear. High-level coupled cluster calculations reported in this work demonstrate that for iron(III)-hydrides, hydrogen atom transfer (HAT) is favored over hydrometalation. The oxidation state of iron makes a remarkable difference in the reactivity of the iron-hydride such that ferric FeIII−H is much more reactive in HAT than ferrous FeII−H. Akin to iron(IV)-oxo, exchangeenhanced reactivity (EER) dictates the intrinsic spin HAT reactivity of iron(III)hydride. However, it is not two-state reactivity (TSR) but single-state reactivity (SSR) that operates in HAT with iron(III)-hydride. The reactivity insights gained herein for alkyl liberation from iron-alkyls may have profound mechanistic implications on the iron-dependent bioorganometallic radical chemistry in radical SAM enzymes. KEYWORDS: hydrogen atom transfer, iron-hydride, alkyl radical, exchange-enhanced reactivity, single-state reactivity, two-state reactivity, spin state, oxidation state
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Scheme 1. Mechanistic Scenario of Alkyl Radical Generation from (a) Iron-hydride/alkene (b) Iron-oxo/ alkane
adical generation is the initiating step in radical reactions. As a basis for radical chemistry, a new radical generation strategy and its mechanistic understanding are of fundamental importance.1 Bearing a variety of radical coupling and relay transformations, alkyl carbon radicals constitute versatile reactive intermediates to construct aliphatic C−C and C−X (X = heteroelement) bonds in organic and organometallic chemistry.2 To provide alkyl radicals, first-row base metals like manganese, iron, cobalt, nickel, and copper have special advantage because of their tendency to mediate single-electron redox processes, rather than two-electron redox processes often mediated by their second/third-row congeners of noble metals. In particular, growing out of the seminal work of Drago and Mukaiyama on cobalt catalysis in the 1980s,3 the reactions based on iron-hydrides and alkenes recently became an appealing approach to access alkyl radicals for utilizing their rich chemical transformations,4−9 including the applications in total synthesis of medicinal natural products like Vinblastine by Boger.9b However, the mechanistic understanding for this radical-generating process is not well-established yet, which hinders the further development of this fascinating chemistry. Generally, two mechanistic pathways can be envisioned in alkyl radical generation from iron-hydride and alkene. One is inner-sphere migratory insertion (MI) of alkene into a Fe−H bond (i.e., hydrometalation), which furnishes alkyl-iron species, followed by Fe−C bond homolytic cleavage to generate alkyl radical in a stepwise manner (Scheme 1a). The other, which was first noted by Norton,10 but did not © 2019 American Chemical Society
draw broad attentions in the community of homogeneous catalysis and organometallic chemistry until very recently as Received: April 25, 2019 Revised: May 23, 2019 Published: June 7, 2019 6080
DOI: 10.1021/acscatal.9b01691 ACS Catal. 2019, 9, 6080−6086
Letter
ACS Catalysis
is separated from the intermediate-spin and low-spin states by large gaps of tens of kcal/mol (the electronic configurations of three spin states of 1 are shown in Figure 2). Along HAT
suggested by Shenvi and Herzon with the corresponding cobalt and manganese catalysts,11 is outer-sphere hydrogen atom transfer (HAT) from iron-hydride to alkene to directly render an alkyl radical (Scheme 1a).2c,4 Interestingly, HAT is the dominant pathway in bioinorganic aliphatic C−H activations by heme and nonheme high-valent iron-oxo species,12,13 which also generate alkyl radical (Scheme 1b). In contrast to the extensive theoretical studies available on HAT by iron-oxo species that have shed light on their reactivities over multiple spin states of iron by the concept of exchange-enhanced reactivity (EER),13,14 there is still no theoretical work addressing the fundamentally important reaction mechanism to produce alkyl radical from ironhydride/alkene. In particular, currently we almost know nothing about the roles and effects of the oxidation and spin states of iron in HAT from iron-hydride to alkene, as well as the possibility of the existence of EER (Scheme 1a). Considering that there is still no direct experimental observation and characterization of the presumed iron-hydride in the reactions, theoretical modeling would become a suitable approach to provide the highly desired mechanistic information. To reliably solve these conundrums, high-level ab initio calculations are necessary to circumvent the caveat of current DFT methods on spin-state energetics involving first-row transition metals.15 In this work, following our continuous interests to understand the fascinating (bio)chemistry and reactivity of iron,16 in particular for HAT,17 by combining high-level ab initio coupled cluster (CC) and DFT approaches,18 we for the first time clarify the mechanistic scenario for alkyl radical generation from iron-hydride/alkene, whereby the reactivity is regulated by iron spin and oxidation states. Furthermore, the factors revealed herein that control the kinetics and thermodynamics of alkyl liberation from iron-alkyl species may have profound implications to carbon radical chemistry of the emerging bioorganometallic iron-alkyl intermediates, so-called Ω, in radical SAM enzymes.19 To resolve the key mechanistic issue of HAT vs MI in alkyl radical generation, we first explored ferric iron(III)-hydride (1) bearing the experimentally often used β-diketonate ligands4−7 featuring an oxygen-rich coordination environment and a weak ligand field. In agreement with this feature, we found that among the three spin states of Fe(III)-H (doublet, quartet, sextet), 1 clearly has a high-spin ground state (Figure 1), which
Figure 2. Electronic configurations of three spin states of Fe(III)-H species 1.
pathway from 1 to ethylene to render alkyl radical, the highspin sextet state has the lowest HAT transition state (TS) 6 TS1−2, with a free energy barrier of 24.0 kcal/mol (the frontier orbitals with interaction between Fe−H and CC moieties for TS1−2 are depicted in Figure 3). The identification of the
Figure 3. Frontier orbitals with interaction between Fe−H and CC moieties in three spin states of HAT transition state TS1−2.
high-spin state as the dominant state in HAT is also supported by the calculated H/D kinetic isotope effect (KIE) of 1.6, 1.9, and 2.4 for sextet, quartet, and doublet, respectively, when compared with the experimental value of 1.5.5d HAT on the high-spin state is exergonic by 16.1 kcal/mol, which causes reverse HAT kinetically impossible by having a prohibitively high barrier of around 40 kcal/mol. This result is in line with the previous experimental conjecture that HAT in such system is irreversible, which is the basis of Baran’s rationalization for the observed normal KIE (>1) rather than the inverse KIE (
