Facilitating the Ferration of Aromatic Substrates through Intramolecular Sodium Mediation

Abstract

Exploiting cooperative effects between Na and Fe II centres present in tris(amide) ferrate complexes has led to the chemoselective ferration of pentafluorobenzene, benzene, toluene, anisole, and pyridine being realised at room temperature. The importance of this bimetallic partnership is demonstrated by neither the relevant sodium amide (NaHMDS or NaTMP) nor the Fe II amide Fe(HMDS) 2 efficiently metallating these substrates under the conditions of this study. By combining NMR studies with the isolation of key intermediates and DFT calculations, we offer a possible mechanism for how these reactions take place, uncovering a surprising reaction pathway in which the metals cooperate in a synchronised manner. Although the isolated products are formally the result of Fe-H exchange, theoretical calculations indicate that the aromatic substrates undergo Na-H exchange followed by fast intramolecular transmetallation to Fe, thus stabilizing the newly generated aryl fragment.Heterobimetallic amide bases containing a complementary combination of an alkali metal with a less electropositive metal, such as Mg or Zn, have emerged as a powerful class of reagents for selectively deprotonating functionalised arenes. [1] Profiting from the cooperation between the two metals, these bimetallic strategies can offer greater functional group tolerance and special regioselectivities that conventional single-metal bases cannot match. [2] Through the isolation

Lateral Metallation and Redistribution Reactions of Sodium Ferrates Containing Bulky 2,6‐Diisopropyl‐N‐(trimethylsilyl)anilide Ligands

“…It should also be noted that the ferration of pentafluorobenzene by 1 is synergistic in origin since [Fe{N(SiMe 3 )Dipp} 2 ] on its own cannot selectively deprotonate this substrate; whereas the stronger base NaHMDS metallates this substrate albeit nonselectively generating a mixture of decomposition products including saline NaF. Formation of 4 can be envisaged to occur via a similar mechanism to that we have recently reported for [NaFe(HMDS) 3 ] (I), [23] with initial coordination of C 6 F 5 H to Na in 1 which induces the shift of one bridging HMDS amide to Na, facilitating the NaÀ H exchange which is immediately followed by a fast intramolecular trapping of the C 6 F 5 aryl anion by the Fe(II) centre (see Scheme S1 in Supporting Information).…”

“…Our previous reactivity and computational studies on heteroleptic sodium ferrates containing both HMDS and TMP groups have shown that in solution [NaFe (TMP)(HMDS) 2 ] is actually in equilibrium with their homoleptic analogues [NaFe(HMDS) 3 ] (I) and [NaFe(TMP) 3 ]. [23] A similar process can be proposed to occur for 1 although in this case the steric demand imposed by the N(SiMe 3 )Dipp ligand could favour the cleavage of putative complex [NaFe(HMDS){N(SiMe 3 ) Dipp} 2 ] into its single-metal components NaHMDS and complex Fe{N(SiMe 3 )Dipp} 2 which can be detected spectroscopically (Scheme 1 and S13 in Supporting Information). It should also be noted that Mulvey has reported that related Na and K magnesiate complexes [M I Mg{N(SiMe 3 )Dipp} 2 (nBu)] 1 undergo redistribution in d 8 -THF solution furnishing the relevant alkalimetal amide and [M I N(SiMe 3 )Dipp] and BuMg{N(SiMe 3 )Dipp}.…”

“…Our previous studies in this area have demonstrated reactions to be strongly dependent on the nature of the amide employed. [23] Pentafluorobenzene (C 6 F 5 H) and pyridine (py) were chosen as model substrates. The former is highly activated in terms of pK a value of its sole H centre; [41] whereas the latter is a sensitive electron-deficient substrate for which metallation using conventional polar organometallics can be particularly challenging due to the fragility of their metallated intermediates as well as the difficulty in controlling the regioselectivity of the metal-H exchange.…”

“…[17,19] Recent studies by our group and others have shown that combining iron(II) amides (or alkyls) with a group 1 metal reagent lead to the formation of bimetallic bases (via cocomplexation) capable of promoting FeÀ H exchange reactions of different aromatic substrates. [20][21][22][23][24] Notably, Klett, Mulvey and co-workers have reported a powerful Na/Fe amide combination capable of regioselective 1,4-dideprotonation of benzene. [20] Knochel has detailed a trimetallic system formulated as (TMP) 2 Fe•MgCl 2 • 2 LiCl (TMP = 2,2,6,6-tetramethylpiperidide) for the ferration of a variety of substituted arenes, which in turn undergo cross-couplings with aryl halides.…”

“…[21] Through our own investigations we have found homoleptic sodium ferrates [MFe (HMDS) 3, ] (M = Li, Na) particularly effective for ortho-metallation of sensitive, activated fluoroarenes. [22,24] While structural studies confirm that the products of these reactions are formally the result of a direct FeÀ H exchange, recent mechanistic studies [23] have proposed a cooperative pathway where initially sodiation of the substrate takes place, followed by fast transmetallation to Fe forming more covalent FeÀ C bonds that stabilise the sensitive aryl fragments. Since this process occurs in a bimetallic structure it has been coined intramolecular trans-metaltrapping.…”