Radicals derived from Lewis acid/base pairs

Abstract

While conventional approaches to stabilizing main group radicals have involved the use of Lewis acids or bases, this tutorial review focuses on new avenues to main group radicals derived from combinations of donor and acceptor molecules. Reactions involving the use of both classical Lewis acid–base adducts and frustrated Lewis pair systems are discussed and the subsequent reactivity is considered.

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Liu Leo Liu

Liu Leo Liu is a post-doctoral fellow in Prof. Stephan's group at the University of Toronto. Prior to this, he received his PhD degree in 2016 from a joint program under the supervision of Prof. Yufen Zhao at Xiamen University (2011–2013, 2015–2016) and Prof. Guy Bertrand at University of California, San Diego (2013–2015). He was awarded the National Scholarship for outstanding PhD students in 2014 from the Chinese Ministry of Education. He has published over 50 peer-reviewed papers, and his research spans synthetic and computational chemistry with the focus of unusual main group compounds.

Douglas W. Stephan

Douglas W. Stephan began independent career at the University of Windsor (1982). In 2008 he moved to the University of Toronto as a Professor and Canada Research Chair. A highly successful researcher in inorganic chemistry/catalysis, he is best known for articulating the concept of “frustrated Lewis pairs”. Stephan has received a number of awards. He was named a Fellow of the Royal Society of Canada (2005), a Fellow of the Royal Society (2013, London), a Corresponding Member of North-Rhein-Westfaelia Academy (2014, Germany), and an Einstein Visiting Professor at the Technical University of Berlin (2016–2019) and made the Thomson Reuters Highly Cited List (2014–2018).

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Key learning points

1. The development of Lewis pair chemistry has contributed to advancements in generation of persistent or transient radicals.

2. Frustrated radical pairs have been shown to cleave chemical bonds in a homolytic fashion.

3. Single electron delivery to Lewis pairs leads to transient radical anions that split a variety of chemical bonds.

4. A variety of stable radicals have been achieved via reactions involving frustrated Lewis pairs or classical Lewis adducts.

Introduction

In 1923, Gilbert N. Lewis classified electron-pair donors and electron-pair acceptors as Lewis bases (LBs) and Lewis acids (LAs) respectively.¹ Since then, classical Lewis acid–base adducts (CLAs) derived from the two electron donation from a Lewis base (LB) to a Lewis acid (LA) were thought to be thermodynamically stable and generally unreactive. This paradigm changed in 2006 with the discovery that a reversible activation of H₂ could be mediated by p-(Mes₂P)C₆F₄(B(C₆F₅)₂) (Mes = mesityl).² In this case, the Lewis basic phosphorus and acidic boron centres are sterically encumbered and this precludes the dative bond formation permitting the reaction with H₂. Subsequently this observation was generalized to combinations of LAs and LBs with appropriate steric hindrance to deter dative bonding. Indeed, access to dissociative equilibria has proved sufficient to such frustrated Lewis pairs (FLPs) to react with a wide variety of substrates,^3–6 as well as to effect metal-free hydrogenation catalysis.

Over the last decade the above development of FLP chemistry has been predicated on the notion that the chemistry results from two-electron processes in which the Lewis bases and acids act as two electron donors and acceptors respectively. However, a number of recent studies have either inferred or demonstrated the role of radical pathways in reactions involving Lewis acids and bases, both in FLP chemistry and beyond. At the same time, carbon-based radicals have an extended history dating from the landmark work of Gomberg more than one century ago.⁷ In contrast, main group radicals have received much less attention. The conventional approaches to stabilizing main group radicals has involved the use of LAs or LBs. For example, LA-complexation of a radical donor has been known for some time⁸ and the reactivity of such species has been exploited more recently.^9,10 The complementary approach in which LBs are used to stabilize radicals has also been employed. For example, several recent studies have used singlet carbenes to stabilize main group radicals^11–14 In this tutorial review, we focus on new avenues to main group radicals derived from combinations of donor and acceptor molecules. Reactions involving the use of both CLA and FLP systems are discussed and the subsequent reactivity of the derived radicals is considered.

Donor–acceptor induced homolysis

A unique approach to the generation of a main group radical involves base induced homolysis of an element–element bond. In 2016, Li, Zhu and co-workers¹⁵ described such a strategy involving the transient formation of a donor–acceptor adduct derived from the addition of two equivalents of 4-cyanopyridine to B₂(pin)₂. This prompted homolytic cleavage of the B–B bond affording the pyridine-ligated boryl radical [NCC₅H₄NBpin]˙ 1 (Scheme 1). The donor 4-cyanopyridine behaves as a one-electron acceptor, reminiscent of homolytic cleavage reactions of a base stabilized diborane (4).¹⁶

Scheme 1 Synthesis of a pyridine-ligated neutral boryl radical 1via a homolytic cleavage of the B–B bond in B₂(pin)₂.

In extending this approach Jiao and Zhang showed that the combination of B₂(pin)₂, MeOK and 4-phenylpyridine afforded the novel pyridine-boryl species [PhC₅H₄NBpin(OMe)˙][K] 2 and [(PhC₅H₄N)₂Bpin][K] 3 (Scheme 2).¹⁷ In the absence of MeOK, no radical was observed, inferring that the pyridine-boryl adduct reacts with MeOK to prompt the homolytic B–B bond cleavage to produce 2 and 3. These species behave as super electron donors, and can be used in catalytic radical borylation reactions and reductive cleavage reactions.^17,18

Scheme 2 Synthesis of 2 and 3.

Radical capture by FLPs

Recently, Erker, Grimme, Warren et al. prepared a novel type of aminoxyl radical 4via the reaction of an intramolecular FLP Mes₂PCH₂CH₂B(C₆F₅)₂ with NO (Scheme 3).^19,20 Compound 4 was fully characterized including single crystal X-ray diffraction. The Mulliken spin densities of O and N atoms in 4 are 0.54 and 0.34 a.u., respectively. Shortly thereafter, Erker and co-workers reported analogous reactions leading to a variety of related aminoxyl radicals 5–10 (Scheme 3).^20–22

Scheme 3 Examples of aminoxyl radicals derived from reactions of FLPs with NO.

These aminoxyl radicals were shown to engage readily in H-atom abstraction reactions (Scheme 4). For example, compounds 4 and 8 rapidly reacted with 1,4-cyclohexadiene to afford the corresponding diamagnetic products 11 and 12, respectively, along with the formation of benzene. Compound 7 underwent abstraction of H-atoms with cyclohexene to give 13 and a pair of diastereoisomers of 14 and 15.

Scheme 4 Examples of hydrogen atom abstraction reactions of aminoxyl radicals.

Frustrated radical pairs

A triarylamine radical cation

Although the one-electron oxidation of transition-metal complexes by B(C₆F₅)₃ has been described,^23,24 Wang et al. reported the first example of a one-electron oxidation of a triarylamine (C₆H₃CMe₂)₃N 16 by B(C₆F₅)₃ in 2013 (Scheme 5),²⁵ affording the deep blue triarylamine radical cation 17. Although the salt of the weakly coordinating alanate 17[Al(OR_F)₄] (OR_F = OC(CF₃)₃) was isolated, the formation of the boron centred radical anion in the reaction with B(C₆F₅)₃ was not confirmed as this species decomposes rapidly (vide infra).²⁶

Scheme 5 Synthesis of 17via a one-electron oxidation by B(C₆F₅)₃.

Phosphine/Lewis acid frustrated radical pairs (FRPs)

Stephan and co-workers have recently reported evidence for a mechanism for FLP reactivity that involves a radical pathway.²⁷ Upon dissolving Mes₃P and E(C₆F₅)₃ (E = B or Al) in very dry toluene or chlorobenzene, the formation of a trace amount of the purple-colored [Mes₃P˙]⁺ was observed. Although the EPR spectrum of the purple solution generated from Mes₃P/B(C₆F₅)₃ displayed a weak signal, the solution generated from the corresponding Al reaction revealed a room-temperature doublet EPR resonance with a g value of 2.0089 and a hyperfine coupling constant of 238 G. This confirmed the presence of [Mes₃P˙]⁺, however, the presumed radical anion [˙E(C₆F₅)₃]⁻ was not observed as it was rapidly quenched by reactions with solvent.^25,26 Nonetheless, these data support the notion of single-electron transfer (SET) equilibria between the FLP and FRP of the form [Mes₃P˙][˙E(C₆F₅)₃]. Generation of these FRPs in the presence of tetrachloro-1,4-benzoquinone (p-O₂C₆Cl₄) prompts the formation of the radical salt [Mes₃P˙]₂[(C₆F₅)₃EOC₆Cl₄OE(C₆F₅)₃] (E = B, 18; Al, 19) (Scheme 6).

Scheme 6 Reactivity of R₃P/E(C₆F₅)₃ toward p-O₂C₆Cl₄ and Ph₃SnH.

These species react further with p-O₂C₆Cl₄ to give the 1,6-addition products [Mes₃POC₆Cl₄OE(C₆F₅)₃] (E = B, 20; Al, 21) (Scheme 6). Alternatively, the FRPs homolytically split the Sn–H bond in Ph₃SnH to give [Mes₃PH][HB(C₆F₅)₃] 22 or [Mes₃PH][(μ-H)(Al(C₆F₅)₃)₂] 23, respectively (Scheme 6), along with (Ph₃Sn)₂. In sharp contrast, the combination of tBu₃P/E(C₆F₅)₃ shows no evidence of radical formation. Indeed, addition of Sn–H to these FLPs prompts heterolytic Sn–H cleavage affording [tBu₃PSnPh₃][HB(C₆F₅)₃] 24 and [tBu₃PSnPh₃][(μ-H)(Al(C₆F₅)₃)₂] 25, respectively (Scheme 6). This contrasting behaviour demonstrates that FLPs can react either via consecutive one-electron steps or via a classic two electron process.

In a recent and related study, the reactivity of the Mes₃P/B(C₆F₅)₃ pair with benzyl peroxide derivatives was shown to proceed to efficiently split the O–O bond in a homolytic fashion, giving radical salts [Mes₃P˙][PhCOOB(C₆F₅)₃] 26, [Mes₃P˙][p-BrC₆H₄COOB(C₆F₅)₃] 27 and [Mes₃P˙][p-MeC₆H₄COOB(C₆F₅)₃] 28 (Scheme 7).²⁸ Control experiments showed that the combination of B(C₆F₅)₃ with the peroxides gave an adduct mixture. These reactions represent the first examples where FLPs react via a SET process affording the homolytic cleavage of a homodiatomic bond. It is also noteworthy that related phosphoniumyl radical cations [Tipp₃P˙]⁺ (Tipp = 2,4,6-triisopropylphenyl) and [Tipp₂MesP˙]⁺ were prepared and structurally characterized by Wang et al.²⁹ employing the weakly coordinating anions such as [Al(OR_F)₄]⁻ (OR_F=OC(CF₃)₃) and [Al(OR_Me)₄]⁻ (OR_Me=OC(CF₃)₂Me).

Scheme 7 Reactivity of Mes₃P/B(C₆F₅)₃ toward benzyl peroxide derivatives.

In 2018, Müller, Klare et al. demonstrated that a SET as a viable reaction pathway for silylium ion/phosphine Lewis pairs (Scheme 8). For example, in solution, both FLPs consisting of R₃P/[(Me₅C₆)₃Si][B(C₆F₅)₄] (R = Tipp or Mes) and CLAs derived from the combination of R₃P/[iPr₃Si(odcb)][B(C₆F₅)₄] (odcb = 1,2-dichlorobenzene) promote the establishment of a SET equilibrium mixture with the corresponding radical pairs 29–31, indicating that complete frustration of the Lewis pairs is not necessarily a prerequisite for such SET processes.

Scheme 8 One-electron oxidation of phosphines in silylium ion/phosphine Lewis pairs.

Single electron transfer in a Lewis acid–base reaction

More recently, the group of Müller disclosed that a Lewis acid–base reaction between the nucleophilic hafnocene-based germylene 32 and B(C₆F₅)₃ leading to a Ge-B CLA 33 is initiated by a SET process (Scheme 9).³⁰ The radical salt 34 generated by a SET from the germylene to B(C₆F₅)₃ was identified by EPR and UV-vis spectroscopy. In addition, the nature of the radical cation was confirmed via independent synthesis of the [B(C₆F₅)₄]⁻ salt via the reaction of 32 with [Ph₃C][B(C₆F₅)₄]. This work provided evidence for a SET in CLA formation reactions.

Scheme 9 Synthesis of 33via a radical complex 34.

Electron transfer in FLP-reactions

C–H activation by FRPs

Prior to the recognition of the possibility of a radical pathway for FLP reactivity, it was noted that combination of B(C₆F₅)₃ and PMes₃ generated a faintly purple solution. While early efforts to support a radical pathway were unsuccessful, in 2013, unequivocal evidence of highly reactive transient FRPs of the form [R₃P˙][˙O(Al(C₆F₅)₃)₂] (R = tBu or Nap, Nap = naphthyl) was obtained.³¹ Generated from the reactions of R₃P and Al(C₆F₅)₃ in a molar ratio of 1 : 2 with N₂O (1 atm) (Scheme 10), these FRPs were shown to effect C–H bond activation. In the case of R = tBu, a C–H bond of the tBu group was readily activated to form [tBu₂PMe(C(CH₂)Me)][(μ-OH)(Al(C₆F₅)₃)₂] 35, whereas for R = Nap, the intermolecular activation of toluene or bromobenzene afforded [Nap₃PCH₂Ph][(μ-OH)(Al(C₆F₅)₃)₂] 36 or [Nap₃PC₆H₄Br][(μ-HO)(Al(C₆F₅)₃)₂] 37, respectively (Scheme 10). These reactions proceeded via the corresponding FLP-N₂O adducts, as supported by isolation of the species tBu₃P(N₂O)Al(C₆F₅)₃ using the equal molar portion of tBu₃P and Al(C₆F₅)₃. The H atom in the anion [(μ-HO)(Al(C₆F₅)₃)₂]⁻ was derived from hydrogen atom abstraction from the toluene solvent by the transient radical anion [(μ-O˙)(Al(C₆F₅)₃)₂]⁻.

Scheme 10 C–H bond activation by transient FRPs.

Borocyclic radicals via H₂ activation

It is well known that carbonyl–oxygen atoms form adducts with Lewis acids.³² Nonetheless, the equilibrium access to Lewis pairs provides a pathway to reaction with H₂ resulting in carbonyl hydrogenation.³³ In a similar sense, Stephan et al. in 2016 reported that the reaction of phenanthrene-9,10-dione with B(C₆F₅)₃ in toluene led to formation of a Lewis acid–base adduct (C₆F₅)₃B(O₂C₁₄H₈) featuring a tetracoordinated boron centre.³⁴ Remarkably, treating the above reaction mixture with H₂ (4 atm) at 110 °C resulted in the formation of two products, the major one being [(C₆F₅)₂B(O₂C₁₄H₈)]˙ 38 together with the minor product (C₆F₅)B(O₂C₁₄H₈) 39 (Scheme 11). The paramagnetic nature of 38 was confirmed by EPR spectroscopy which revealed hyperfine coupling to the ¹¹B atom (a_B = 2.58 G) and to hydrogen atoms with a_H = 3.39, 0.00, 2.43, and 1.01 G. These data were consistent with DFT calculations of the spin density showing the delocalization of the unpaired electron over the phenanthrene backbone.

Scheme 11 Synthesis of a borocyclic radical 38via an FLP hydrogenation.

A mechanistic study showed that initially the FLP-hydrogenation of the dione proceeds giving phenanthrene-9,10-diol. This diol reacts with the dione to afford 9,10-phenanthrenequinhydrone radical that readily coordinates B(C₆F₅)₃ to form a paramagnetic Lewis acid–base adduct, followed by protonation of one of the C₆F₅ rings affording 38 and HC₆F₅. Alternatively, if the reduced diol reacts with B(C₆F₅)₃, double protodeborylation affords the minor product 39.

The analogous reactions of B(C₆F₅)₃ with pyrene-4,5-dione,³⁴N-(2,6-dimethylphenyl)-phenanthreno-iminoquinone³⁵ or N,N-di-p-tolylphenanthrene-9,10-diimine³⁵ under the atmosphere of H₂ (4 atm) at 110 °C led to the formation of the related stable borocyclic radical 40–42, respectively (Scheme 12). Notably, the borocyclic radicals 38 and 40–42 are stable towards moisture and oxygen, presumably due to the delocalization of the unpaired electron over the aromatic backbone. Nevertheless, the one-electron chemical reduction of 38 or 40 with cobaltocene generated the corresponding cobaltocenium borate salts.³⁴

Scheme 12 Stable borocyclic radicals prepared via FLP hydrogenations.

In an ensuing work, the reactivity of 38 with a variety of nucleophiles was probed (Scheme 13).³⁶ The LUMO of 38 primarily involves π*-antibonding orbitals over the phenanthrene backbone, prompting a reaction with Ph₃P to give two regioisomeric zwitterions, 1-(Ph₃P)C₁₄H₇O₂B(C₆F₅)₂43 and 3-(Ph₃P)C₁₄H₇O₂B(C₆F₅)₂44, coupled with the related boronic ester 39 and HC₆F₅. Similarly, the reaction of 38 with tBu₃P afforded the zwitterion 3-(tBu₃P)C₁₄H₇O₂B(C₆F₅)₂45 and the salt [tBu₃PH][C₁₄H₈O₂B(C₆F₅)₂] 46, while reaction with N-heterocyclic carbene IMes or quinuclidine gave 3-(IMes)C₁₄H₇O₂B(C₆F₅)₂47 and [IMesH][C₁₄H₈O₂B(C₆F₅)₂] 48 or 3-(C₇H₁₃N)C₁₄H₇O₂B(C₆F₅)₂45 and [H(NC₇H₁₃)₂][C₁₄H₈O₂B(C₆F₅)₂] 50, respectively (Scheme 13). In contrast, treatment of 38 with DMAP led to attack at the carbonyl carbon atoms, affording [9,10-(DMAP)₂C₁₄H₈O₂B(C₆F₅)₂][C₁₄H₈O₂B(C₆F₅)₂] 51 (Scheme 13).

Scheme 13 Reactivity of 38 toward nucleophiles.

A neutral aminyl radical from disulfide activation

The FLP system consisting of the nitrogen based Lewis acidic nitrenium cation 52 with tBu₃P has been shown to react (PhS)₂ to afford the persistent neutral aminyl radical, [(p-ClC₆H₄)N₂(PtBu₃)]˙ 53 and the salt [PhSPtBu₃][BF₄] 54 (Scheme 14).³⁷ This is reminiscent of the dione/borane reaction with H₂ described above, suggesting that the concerted FLP action on the disulphide prompts electron transfer. It is noteworthy that the radical 53 was also accessible via a more conventional reduction of 52 with cobaltocene or PhSNa.

Scheme 14 Synthesis of an aminyl radical 53via FLP activation of diphenyl disulfide.

Transient donor–acceptor radicals

In 2016, the Erker group described the selective oxidation of the intramolecular amine/borane FLP, [C₅H₆Me₄N(CH₂)₃B(C₆F₅)₂], with dioxygen (Scheme 15).³⁸ In this case, the resulting tetrahydroisoxazolium borate salt [C₅H₆Me₄N(CH₂)₃O] [C₅H₆Me₄N(CH₂)₃B(C₆F₅)₂OB(C₆F₅)₃] 56 was formed via a series of transient radical intermediates. Initially an endergonic generation of alkyl radicals prompts the propagation step generating a borylperoxide intermediate, leading to the formation of 56 in an overall thermodynamically favourable process (−59.5 kcal mol⁻¹) (Scheme 15).

Scheme 15 Oxidation of an intramolecular amine/borane FLP with dioxygen. Free energies are given in kcal mol⁻¹.

A related work described by Erker, Studer et al. described that the reaction of the boryldiene CH₂=C(Me)CH=CHB(C₆F₅)₂57 with two equivalents of TEMPO yielded species 58 featuring a zwitterionic four-membered ring, in which two TEMPO radicals added to the boryldiene starting material (Scheme 16).³⁹ The authors proposed that the initial coordination of TEMPO to the Lewis acidic boron centre affords a transient radical that undergoes cyclization and then couples a second TEMPO to give the product 58. Trapping of TEMPO at the terminal position is presumably sterically driven. Similarly, the cyclopropyl-substituted alkenyl borane, C₃H₅CH=CHB(C₆F₅)₂59 was shown to react with two equivalents of TEMPO affording the ring-opening product 60 (Scheme 16). This observation supported the generation of the analogous radical intermediates. Indeed the scope of analogous reaction with TEMPO radical was extended in 2017.⁴⁰

Scheme 16 Synthesis of 58 and 60via transient radicals.

In a recent work, the FLP derived from a nitrogen-centered LA, namely a cyclic (alkyl)(amino)nitrenium cation, [C₆H₄CPh₂N₂tBu][BF₄] 61, and tBu₃P was shown to react with dipropyl disulfide (PrS)₂.⁴¹ One product is the salt [tBu₃PSPr][BF₄]. The other product derived from the heterolytic S–S cleavage, [(C₆H₄)(NtBu)N(SPr)CPh₂], was not observed but instead, the reaction affords a mixture of (tBuS)₂, (tBuSSPr), Pr₂S, [C₆H₄CPh₂N₂] 62 and [C₆H₄CPhN₂Ph] 63, consistent with a radical chain pathway (Scheme 17).

Scheme 17 FLP reactivity of tBu₃P/61 with (PrS)₂ leading to a spontaneous radical chain degradation.

Electron transfer to an acid/base adduct

Ferrocene/Lewis pair systems

Another approach to reactive radicals is derived from the addition of a one-electron donor with a Lewis donor/acceptor combination. This concept was first demonstrated by Agapie and Henthorn who reported reactions of ferrocene/B(C₆F₅)₃ pairs with dioxygen which afforded [Cp′₂Fe]₂[(C₆F₅)₃BOOB(C₆F₅)₃] (Cp′ = Cp 64 or Cp* 65); the first examples of dianionic boron peroxide salts (Scheme 18).⁴² Although B(C₆F₅)₃ is inert to ³O₂ over 24 h, the presence of B(C₆F₅)₃ appeared to facilitate the reduction of ³O₂ by ferrocenes. A cyclic voltammetry (CV) study suggested the reaction proceeded via the transient B₂O₂ superoxide intermediate although attempts to access this intermediate were unsuccessful.

Scheme 18 Reactivity of ferrocene/B(C₆F₅)₃ toward dioxygen.

Exploiting a related strategy, Stephan and co-workers exploited such single electron delivery from Cp*₂Fe in the presence of a Lewis acid (E(C₆F₅)₃, E = B or Al) for small molecule activation.⁴³ In this fashion, O–O, S–S, Se–Se, Te–Te, C–H, C–O and Sn–H bonds were cleaved in a homolytic fashion, affording a variety of ferrocenium salts 66–75 featuring novel B- and Al-containing anions (Scheme 19). For example, exposure of a solution of Cp*₂Fe/Al(C₆F₅)₃ to dry ³O₂ immediately resulted in the O–O bond cleavage, giving the salt [Cp*₂Fe]₂[((C₆F₅)₃AlOAl(C₆F₅)₂)₂] 72 with a dianionic Al₂O₂ core. This stands in contrast to the corresponding reaction of Cp*₂Fe/B(C₆F₅)₃ that yields 65 in which the O–O bond remains intact (Scheme 18). The corresponding reactions of Cp*₂Fe/E(C₆F₅)₃ with elemental Te and S₈ afford a unique tricyclic Al₃Te₂ anion and a dianion in which two boron centers are linked by seven sulfur atoms, respectively (Scheme 19).

Scheme 19 Reactivity of Cp*₂Fe/E(C₆F₅)₃ toward small molecule substrates.

Control reactions showed the slow generation of ferrocenium cation in the absence of substrate molecules, consistent with SET from Cp*₂Fe to E(C₆F₅)₃, suggesting that the generated [˙E(C₆F₅)₃]⁻ reacts with substrate. Alternatively, SET to the Lewis acid-substrate adduct is also possible. It is noteworthy that Chen also proposed the generation of the fleeting [˙Al(C₆F₅)₃]⁻ that was followed by decomposition during thermolysis of a C₆D₅Br solution of Al(C₆F₅)₃ with Cp₂Fe at 100 °C for 3 days,⁴⁴ although the radical anion [˙Al(C₆F₅)₃]⁻ was not observed.

In a recent work, this concept of SET was extended to systems based on the transition-metal-based LA; Zn(C₆F₅)₂ (Scheme 20).⁴⁵ In this case, the combination of Zn(C₆F₅)₂ and [(PhC(S)S)₂] gave a weak CLA, while the cleavage of the S–S bond of [(PhC(S)S)₂] was achieved immediately upon mixing the substrate with Zn(C₆F₅)₂ and Cp*₂Fe, leading to a salt [Cp*₂Fe][PhCS₂Zn(C₆F₅)₂] 76. No SET reaction from Cp*₂Fe to Zn(C₆F₅)₂ was observed in the absence of [(PhC(S)S)₂], inferring that single electron delivery from Cp*₂Fe to the CLA prompts the rapid cleavage of the S–S bond.

Scheme 20 Reaction of Cp*₂Fe/Zn(C₆F₅)₂ with [(PhC(S)S)₂].

More recently, the group of Severin reacted Cp′₂Fe/Al(C₆F₅)₃ (Cp′ = Cp* or Cp) with N₂O (Scheme 21), affording salts [Cp’₂Fe][(μ-HO)(Al(C₆F₅)₃)₂] (Cp′ = Cp*, 77; Cp, 79).⁴⁶ At the same time, neutral species 78 and 80 involving the C–H activation of the metallocenes were isolated. These observations indicated the formation of the transient oxyl radical anion [˙OAl(C₆F₅)₃]⁻ that spontaneously abstracts hydrogen atoms from the metallocenes. The ensuing metallocene-based radicals underwent radical/radical coupling reactions leading to 78 and 80. This is further evidenced by the reaction of Ph₃C˙/Al(C₆F₅)₃ with N₂O, wherein [˙OAl(C₆F₅)₃]⁻ was trapped by the excess Ph₃C˙ to give the salt [Ph₃C][Ph₃COAl(C₆F₅)₃] 81.

Scheme 21 Reaction of Cp′₂Fe/Al(C₆F₅)₃ or Ph₃C˙/Al(C₆F₅)₃ with N₂O.

Zinc-containing radical anions

In 2018, related zinc-dione-containing radical anions were prepared via a single electron transfer to donor–acceptor system consisting of dione/Zn(C₆F₅)₂ (Scheme 22).⁴⁵ Specifically, the phenanthrene-9,10-dione or pyrene-4,5-dione donor–acceptor adduct [(C₁₄H₈O₂)Zn(C₆F₅)₂] 82 or [(C₁₆H₈O₂)Zn(C₆F₅)₂] 83 was shown to feature low-lying LUMOs relative to those of the corresponding free diones. One-electron reduction of these adducts with Cp*₂Fe gave the persistent zinc-cyclic radical anions 84 and 85 with counterions of the ferrocenium cation.

Scheme 22 Synthesis and reactivity of zinc-containing radicals.

These salts proved labile undergoing reaction with DMAP to give [Zn(C₆F₅)₂(DMAP)₂] with the regeneration of Cp*Fe and the free corresponding dione (Scheme 22).

Semiquinone radical anions

In a recent and related work, Erker et al. reported that, in the presence of two molar equivalents of B(C₆F₅)₃, p-benzoquinone, 9,10-anthraquinone, acenaphthenequinone or 9,10-phenanthrenequinone reacted with a one-electron donor such as TEMPO, Gomberg dimer and Cp*₂Fe, leading to the formation of a series of isolable doubly O-borylated semiquinone radical anion salts 86–93 (Scheme 23).⁴⁷ In the absence of B(C₆F₅)₃, the corresponding reaction of the studied quinones with TEMPO, Gomberg dimer or Cp*₂Fe did not react. The presence of B(C₆F₅)₃ appeared to facilitate the reduction of the quinones.

Scheme 23 Synthesis of semiquinone radical anions.

Bis(borane)superoxide radicals

In 2017, the group of Erker demonstrated that electron transfer can be effected from TEMPO to boranes in the presence of O₂ (Scheme 24),⁴⁸ affording the salts of the bis(borane)superoxide radical anion [C₅H₆Me₄N=O][˙O₂[B(C₆F₅)₃]₂] 94 and [C₅H₆Me₄N=O][˙O₂[B(p-C₆F₄H)₃]₂] 95 respectively. These species are analogous to the [Cp*₂Fe]⁺ salts reported by Agapie and Henthorn (Scheme 18) (vide supra).⁴² Interestingly, the Gomberg dimer of the trityl radical reacted in a similar fashion to give the salt [Ph₃C][˙O₂[B(p-C₆F₄H)₃]₂] 96 (Scheme 24). These results showcase the advantage of application of TEMPO or the trityl radical for the isolation of these bis(borane)superoxide radical anions. Interestingly, THF or DMSO reacted with 94 prompted the regeneration of TEMPO and O₂ and formation of (THF)B(C₆F₅)₃ or (DMSO)B(C₆F₅)₃, respectively. This observation indicates that displacement of B(C₆F₅)₃ moiety from the anion alters the redox potential of the transient superoxide radical prompting electron transfer to the oxoammonium cation to generate TEMPO and liberating O₂.

Scheme 24 Synthesis and reactivity of a bis(borane)superoxide radical anion.

Conclusion and perspectives

The generation and characterization of radical species in main group chemistry has become more prevalent in the literature recently. Indeed, this tutorial has described a number of strategies involving the combinations of Lewis acids and bases that result in radical reactants or products. These include the induction of element–element bond homolysis, electron transfer between donor and acceptor molecules, the use of FLPs to stabilize or generate reactive radicals, and electron transfer to donor–acceptor adducts. The systems presented herein, also serve to highlight the notion that donor–acceptor interactions are not be limited to classical dative two-electron adduct formation. Thus, while many combinations of Lewis acids and bases form either CLA and FLP combinations and react via a diamagnetic, two-electron pathway, judicious choice of donor–acceptor combinations can afford radical pathways, offering new routes and strategies for the exploitation of main group chemistry in reactivity and synthesis.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

NSERC of Canada is thanked for financial support. DWS is grateful for the award of a Canada Research Chair and a Visiting Einstein Fellowship at TU Berlin.

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