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. Author manuscript; available in PMC: 2022 Jul 27.
Published in final edited form as: Inorg Chem. 2022 Apr 12;61(16):6008–6016. doi: 10.1021/acs.inorgchem.1c03686

Aerobic Oxidation Reactivity of Well-Defined Cobalt(II) and Cobalt(III) Aminophenol Complexes

Jiaqi Liu 1,†, Shannen C Lorraine 1, Brian S Dolinar 1, Jessica M Hoover 1,*
PMCID: PMC9328405  NIHMSID: NIHMS1822555  PMID: 35414172

Abstract

This article describes the synthesis and reactivity studies of three cobalt complexes bearing aminophenol-derived ligands without nitrogen substitution: CoII(tBu2APH)2(tBu2AP)2 (1), Co2III(tBu2APH)2(tBu2AP)2(μ-tBu2BAP)2 (2), and CoIII(tBu2AP)3 (3) (tBu2APH = 2-amino-4,6-di-tert-butylphenol, tBu2AP = 2-amino-4,6-di-tert-butylphenolate, μ- tBu2BAP = bridging 2-amido-4,6-di-tert-butylphenolate). Stoichiometric reactivity studies of these well-defined complexes demonstrate the catalytic competency of both CoII and CoIII complexes in the aerobic oxidative cyclization of tBu2APH with tert-butyl isonitrile. Reactions with O2 reveal the aerobic oxidation of CoII complex 1 to generate the CoIII species 2 and 3. UV-visible time-course studies and EPR spectroscopy indicate that this oxidation proceeds through a ligand-based radical intermediate. These studies represent the first example of well-defined cobalt-aminophenol complexes that participate in catalytic aerobic oxidation reactions and highlight a key role for a ligand radical in the oxidation sequence.

Graphical Abstract

graphic file with name nihms-1822555-f0001.jpg

Three unique cobalt(II) and cobalt(III) complexes bearing aminophenol-derived ligands without nitrogen substitution were synthesized and demonstrated to be catalytically competent in the aerobic oxidative cyclization of 2-amino-4,6-di-tert-butylphenol with tert-butylisonitrile. The cobalt(III) species is generated from the aerobic oxidation of the isolated cobalt(II). Spectroscopic studies indicate that this oxidation proceeds through a ligand-based radical species, which serves as a key reaction intermediate in the oxidative coupling with isonitriles.

INTRODUCTION

Cobalt complexes are attractive catalysts for aerobic oxidation reactions due to their well-recognized ability to activate molecular oxygen.1,2 Catalytic methods have been devised for the aerobic oxygenation of a variety of organic substrates including alkenes,3 phenols,4 amines,5 sulfides6 and phosphines.7 To achieve efficient turnover, these reactions often rely on the inclusion of co-reductants, such as aldehydes or silanes, or redox-active cofactors, such as NHPI8 or quinone9 (NHPI = N-hydroxyphthalimide). In the case of quinone-based redox-mediators, a CoIII-OO• intermediate abstracts a hydrogen atom from hydroquinone to generate the semiquinone intermediate and ultimately the quinone, which serves to re-oxidize a Pd or Ru catalyst (Scheme 1a).10

Scheme 1.

Scheme 1.

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Intermediacy of Phenoxyl Radicals for HAA in Select (a) Pd- and (b) Cu-Catalyzed Aerobic Oxidation Reactions

A related enzyme-inspired11–14 approach uses redox-active ligands, such as ortho-aminophenols, to enable catalytic aerobic oxidation reactions.15–16 In these systems, an aerobically generated ligand radical is responsible for a key hydrogen atom abstraction (HAA) step. For example, the aerobic alcohol oxidation reaction developed by Wieghardt and co-workers17 has been suggested to proceed via rate-determining C-H HAA of the bound alkoxide by a ligand radical (Scheme 1b). The aerobic generation of the ligand radical which then undergoes HAA is reminiscent of the oxidation of H2Q by CoOO• described above, making the use of redox-active ligands an attractive alternative for the development of efficient Co-catalyzed aerobic oxidation reactions.

Stoichiometric studies of catechol- and aminophenol-ligated Co complexes have supported the possible role of ligand non-innocence in catalytic oxidation reactions.18–20 Of particular interest, Weighardt and coworkers reported the amino-phenol derived CoIII(LISQ)3 complex (LISQ = N-phenyl-4,6-tert-butyl-imino-semiquinonanto) (Scheme 2a).19a In this system, aerobic oxidation of the CoII and N-phenyl-4,6-di-tert-butylaminophenol pre-cursors led to oxidation of both the Co center and the ligand to yield the iminosemiquinonato complex.

Scheme 2.

Scheme 2.

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Well-Defined Co Species Isolated from Aerobic Oxidation Reactions reported by the groups of (a) Wieghardt, (b) MacBeth, and (c) Fiedler

MacBeth and coworkers have reported a bimetallic Co complex bearing the redox-active bis(2-isobutyrylamidophenyl)amine ligand (HN(o-PhNHC(O)iPr)2) and shown it to activate O2 for the catalytic oxygenation of triphenylphosphine and the deformylation of 2-phenylpropionaldehyde via a low-spin CoII-superoxide intermediate (Scheme 2b).21 In an elegant study, Fiedler and coworkers have isolated a rare example of a cobalt(III)-alkylperoxo species resulting from catecholase-type reactivity of a cobalt-superoxo (Co-OO•−) intermediate (Scheme 2c).22

Despite the notable advances in the synthesis, characterization, and reactivity studies of Co complexes bearing catechol- and aminophenol-derived ligands, the application of these complexes in catalysis remains limited. To date, the only work demonstrating the reactivity of cobalt-aminophenolate complexes was reported by Soper and co-workers,23 who described a square planer CoIII complex capable of mediating a Negishi-like cross-coupling reaction of an alkyl halide with an organozinc reagent (Scheme 3a). This example, however, is a stoichiometric redox-neutral coupling performed under anaerobic conditions. We are unaware of any examples of catalytic aerobic oxidation reactions employing Co-aminophenol complexes.

Scheme 3.

Scheme 3.

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Cobalt-Mediated (a) C-C Coupling and (b) Oxidative Cyclization Reactions Employing Redox-Active Aminophenol Ligands

We recently reported the aerobic oxidative coupling of substituted ortho-aminophenols with isonitriles (CNR) and proposed the reaction to proceed through an intermediate in which the aminophenol ligand plays a key role in the O2 activation step (Scheme 3b).24 In this work, we disclose three new CoII- and CoIII-aminophenol complexes and demonstrate that both CoII and CoIII complexes are catalytically active in this aerobic coupling reaction. The stoichiometric reactivity of these species supports O2 activation by CoII to generate an aminophenol-ligand radical, which then undergoes coupling with isonitrile.

RESULTS AND DISCUSSION

Synthesis and Characterization of CoII(tBu2APH)2(tBu2AP)2 (1).

We first targeted the Co species bearing the unsubstituted ortho-aminophenol ligand; however, attempts to isolate this complex resulted in product mixtures. Instead, 2-amino-4,6-di-tert-butyl phenol (tBu2APH) was used for the synthesis of the well-defined cobalt complexes. The CoII complex CoII(tBu2APH)2(tBu2AP)2 (1) was synthesized from CoCl2 and tBu2APH in the presence of triethylamine (Et3N) in acetonitrile under an inert atmosphere (Scheme 4). CoCl2 was chosen as the cobalt source for its greater solubility compared to Co(OAc)2, which was employed under the original catalytic oxidative cyclization conditions. Complex 1 was obtained in the highest yield (93%) when a 1:4 metal to ligand ratio was employed, however 1 was also formed as the predominant Co species when M:L ratios of 1:1, 1:2, 1:3 and 1:5 were used (Table S1).

Scheme 4.

Scheme 4.

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Synthesis of CoII(tBu2APH)2(tBu2AP)2 (1).

The paramagnetic CoII complex 1 was characterized by elemental analysis, X-ray crystallography, NMR and absorption spectroscopies as well as cyclic voltammetry. The 1:4 metal to ligand ratio of the isolated compound was confirmed by combustion analysis and X-ray crystallography. Light green-yellow single crystals suitable for X-ray diffraction were obtained by slow evaporation of the reaction solvent under anaerobic conditions. The solid-state structure contains a mononuclear CoII center in a distorted octahedral geometry. Co is bound by two monodentate aminophenol ligands (tBu2APH) oriented cis to one another and two bidentate aminophenolate ligands (tBu2AP, Figure 1).

Figure 1.

Figure 1.

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The structure of CoII(tBu2APH)2(tBu2AP)2 (1). All non-hydrogen atoms are drawn at 50% thermal probability ellipsoids. All hydrogen atoms except those on heteroatoms are omitted for clarity. Selected bond distances (Å): Co1-N1 2.162(3), Co1-N2 2.231(15), Co1-O1 1.986(3), O1-C2 1.330(5), N1-C1 1.415(14), C1-C2 1.396(6), C2-C3 1.405(6), C3-C4 1.368(6), C4-C5 1.371(7), C5-C6 1.365(6).

The bond lengths and angles show no evidence of a quinoidal-type distortion and point toward aromatic tBu2AP ligands. The aromaticity of the ligands is supported by the electronic spectrum of complex 1, which displays an absorption maximum in the UV region (λmax = 381 nm, ε = 0.8×104 M−1cm−1, Figure S8), characteristic of aromatic aminophenol ligands.26 The paramagnetic nature of complex 1 is evident from NMR spectroscopy. The 1H NMR spectrum of compound 1 features two broad peaks around 30 ppm and 50 ppm (Figure S1), while the magnetic susceptibility of the complex (μeff = 4.04 μB) indicates a high spin S=3/2 Co center.25

The observed formation of complex 1 regardless of the Co:L ratio contrasts literature reports in which the 1:319b and 1:2 complexes are isolated.19d Furthermore, prior examples of Co-AP complexes include bulky substituents on the nitrogen of the AP ligand.19d,e,26 This substitution likely prevents formation of the corresponding 1:4 complexes and instead favors the 1:2 and 1:3 coordination complexes. Complex 1, as well as complexes 2 and 3 (vide infra), are the first examples of isolable Co complexes ligated by only aminophenol-derived ligands with unsubstituted NH2 groups. These species are also the catalytically relevant complexes as N- substitution would prevent formation of the benzoxazole products (Scheme 3b). The tert-butyl groups on the aromatic rings, however, are crucial to obtain a stable and isolable CoII complex.

Oxidation of Complex 1.

Wieghardt and coworkers have shown the CoII complex bearing 2-amino-4,6-di-tert-butyl thiophenol ligands to undergo solid-state oxidation upon exposure to air.19d We sought to explore the corresponding oxidation of complex 1. The electrochemical oxidation of 1 was measured via cyclic voltammetry in DMSO. The resulting voltammogram displayed a single quasi-reversible redox event at E1/2 = 0.145 V versus Ag/AgNO3 (Figure S9). The inclusion of Et3N has a dramatic influence on the voltammogram leading to a new wave at lower potentials (Epa = −0.10 V vs Ag/AgNO3) suggestive of a possible ligand-based oxidation that is facilitated by deprotonation in the presence of base (Figure S10).

The aerobic oxidation of complex 1 was probed by 1H NMR spectroscopy. Introduction of a headspace of air into a solution of 1 in C6D6 led to the rapid formation of a diamagnetic species (within 5 min), followed by its slow decomposition over an extended period of time (hours). The resulting diamagnetic CoIII species was determined to be the dinuclear complex Co2III(tBu2APH)2(tBu2AP)2(μ-tBu2BAP)2 (2) (Scheme 5a) following the independent synthesis from the solid-state air oxidation of 1, described below. Conducting the analogous aerobic oxidation of 1 in DMSO led instead to the formation of the mononuclear CoIII complex CoIII(tBu2AP)3 (3) (Scheme 5b). Complex 3 was also obtained from the continued conversion of dimeric 2 in situ in DMSO. The syntheses, characterization and reactivity studies of 2 and 3 are described below.

Scheme 5.

Scheme 5.

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Synthesis of (a) Co2III(tBu2APH)2(tBu2AP)2(μ-tBu2BAP)2 (2) from 1 and CoIII(tBu2AP)3 (3) from (b) 1 and (c) 2

Synthesis and Characterization of Co2III(tBu2APH)2(tBu2AP)2(μ-tBu2BAP)2 (2).

Upon exposure of solid 1 to air, a color change from light grey to the shiny dark violet color of 2 was observed. Plate-shaped single crystals were obtained by slow diffusion of pentane into a concentrated solution of 2 in CH2Cl2 under an anaerobic atmosphere. The X-ray crystal structure reveals a dimeric complex in which each cobalt center is ligated by three aminophenol-derived ligands with distinct coordination modes (Figure 2). Each Co center bears a neutral aminophenol ligand (tBu2APH), a monoanionic aminophenolate ligand (tBu2AP), and a bridging amidophenolate ligand (μ-tBu2BAP) connecting the two cobalt centers via the NH group. The Co-N bond lengths for the bidentate and bridging aminophenol ligands are similar with values of 1.9373(15) Å and 1.9172(14) Å , respectively. Both distances are shorter than the Co-N bond distance of the monodentate aminophenol ligand (2.0524(15) Å). The Co-O bond lengths for the bidentate and bridging ligands are also similar with lengths of 1.9176(12) Å and 1.9104(12) Å , respectively. Both bond lengths are significantly longer than those measured for the related tris(o-iminosemiquinone) cobalt(III) complex (1.8784(9) – 1.8960(9) Å).19a The bond lengths of complex 2 revealed no significant elongation or shortening of C-N and C-O bonds, suggesting aromatic aminophenol ligands and the absence of ligand radicals in this cobalt complex.19b

Figure 2.

Figure 2.

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The ORTEP structure of Co2III(tBu2APH)2(tBu2AP)2(μ-tBu2BAP)2 (2). All non-hydrogen atoms are drawn at 50% thermal probability ellipsoids. All hydrogen atoms except those on heteroatoms are omitted for clarity. Selected bond distances (Å): Co1-N1 1.9373(15), Co1-N2 2.0524(15), Co1-N3 1.9172(14), Co1-O1 1.9176(12), Co1-O3 1.9104(12), O1-C2 1.331(2), O2-C30 1.365(2), O3-C16 1.362(2), N1-C1 1.458(2), N2-C29 1.454(2), N3-C15 1.441(2).

The 1H NMR spectrum of the crystals of 2 dissolved in C6D6 under an anaerobic atmosphere revealed a diamagnetic Co species with a 1:3 metal to ligand ratio, in good agreement with the single crystal data (Figure 3). The spectrum features six distinct signals in the aromatic region as well as six different tBu resonances between 1.3–1.5 ppm. Six broad peaks were also observed between 2.5–5.5 ppm, and deuteration with D2O / MeOD confirmed these to be exchangeable NH and OH protons (Figures 3 and S4). Absorption spectroscopy of 2 measured in CH2Cl2 presented two broad bands around 520 nm (ε = 5.8×102 M−1 cm−1) and 580 nm (ε = 5.8×102 M−1 cm−1), assigned as charge transfer bands (Figure S8).

Figure 3.

Figure 3.

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1H NMR spectrum of Co2III(tBu2APH)2(tBu2AP)2(μ-tBu2BAP)2 (2) in C6D6 with the signals resulting from exchangeable NH and OH protons highlighted in blue.

Synthesis and Characterization of CoIII(tBu2AP)3 (3).

The batch isolation of the monomeric CoIII(tBu2AP)3 complex (3) was achieved by slow oxidation of the low-valent complex 1 in DMSO under an air atmosphere (Scheme 5b). The limited solubility of 3 drives the oxidation towards a single species allowing for the selective conversion to 3. Dark violet single crystals suitable for X-ray diffraction were formed during the oxidation. Structural analysis revealed a Co center coordinated by three aminophenolate (tBu2AP) ligands in a distorted octahedral geometry (Figure 4). The three tBu2AP ligands each exist in a unique coordination environment giving the structure overall C1 symmetry. The Co-O (1.8851(12), 1.9012(12) and 1.9047(12) Å) bond lengths are significantly shorter than those measured for the aminophenolate ligand of Co(TpR2)(tBu2APH) (R = Ph, Co-O = 1.9301(17) Å; R = Me Co-O = 1.9766(10) Å),22 likely due to the higher oxidation state of the CoIII center. The Co-N (1.9394(14), 1.9623(14), and 1.9451(14) Å) bond lengths are also significantly shorter than those measured in the same complexes (R = Ph, Co-N = 2.154(2) Å; R = Me, Co-N = 2.1292(13) Å). The related tris(o-iminosemiquinone) cobalt(III) complex reported by Weighardt and coworkers19a contains Co-O and Co-N bonds (Co-O = 1.878(1) - 1.896(1) Å, Co-N = 1.918(1) – 1.946(1) Å) that are similar to those of 3. The aromatic C-C bond distances of 3 (1.377(2) Å – 1.424(2) Å) are similar to those calculated for the neutral aminophenol ligand (1.38–1.41 Å)27 and indicate the absence of ligand radical character. Complex 3 was further characterized by combustion analysis and NMR and UV-visible spectroscopies.

Figure 4.

Figure 4.

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The ORTEP structure of CoIII(tBu2AP)3 (3). All non-hydrogen atoms are drawn as 50% thermal probability ellipsoids. Solvent molecules and all hydrogen atoms except those on heteroatoms are omitted for clarity. Selected bond distances (Å): Co1-N1 1.9394(14), Co1-N2 1.9623(14), Co1-N3:1.9451(14), Co1-O1 1.8851(12), Co1-O2 1.9012(12), Co1-O3 1.9047(12), C1-N1 1.460(2), C15-N2 1.461(2), C29-N3 1.459(2), C6-O1 1.332(2), C20-O2 1.330(2), C34-O3 1.335(2), C1-C2 1.377(2), C2-C3 1.400(2), C3-C4 1.398(2), C4-C5 1.401(2), C5-C6 1.410(2), C1-C6 1.401(2).

Intermediacy of a Ligand Radical.

The generation of CoIII species 2 and 3 from the aerobic oxidation of the low valent complex 1 indicates the ability of CoII complex 1 to activate O2. In related systems, CoII has been shown to activate O2 to yield CoIII-peroxide,28 -alkylperoxo or superoxo intermediates.22 The possible formation of radical intermediates in the aerobic oxidation of 1, was probed with EPR spectroscopy. A solution of complex 1 in CH2Cl2 under N2 was exposed to air for 5 seconds and then frozen. The spectrum of the frozen solution showed an 8-line pattern characteristic of an S = 1/2 system with coupling of a single electron to the 59Co center (I = 7/2) and A values indicative of a ligand-centered spin (Figure 5). These data suggested the formation of a low-spin CoIII ligated by either an aminophenol-centered radical or a superoxide radical.

Figure 5.

Figure 5.

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Experimental EPR data and simulation for CoII(tBu2APH)2(tBu2AP)2 (1) after exposure to air. Conditions: 1 mM complex 1 in CH2Cl2. The sample was prepared inside a N2 filled glovebox and the spectrum was taken immediately after the sample was exposed to air then frozen in liquid N2. Spectrum measured at 77 K. Final fit parameters: g(z) = 2.013, g(y) = 1.996, g(x) = 1.989; A(zz) = 21.5 MHz, A(yy) = 90.9 MHz, A(xx) = 21.8 MHz (coupling to 59Co, I = 7/2, 100% natural abundance).

A cobalt-superoxide intermediate is expected to be very short-lived and likely to undergo a rapid intramolecular hydrogen-atom transfer to generate a ligand phenoxyl radical coupled to a low spin CoIII center (Scheme 3b). The hyperfine coupling constants measured in the oxidation of 1 with O2 are in a good agreement with the reported CoIII salen species in which the ligand phenoxyl radical is coupled to the cobalt center.29 Our results combined with the literature precedent indicate that a phenoxyl radical or a delocalized carbon-centered ligand radical may exist in our system as a result of O2 activation.

The possible involvement of an aminophenol ligand radical was further probed by UV-visible spectroscopy. Introduction of air into a solution of 1 in THF at −78 °C showed no spectroscopic changes (Figure S15). At room temperature in CH2Cl2, however, treatment of 1 with air resulted in the rapid generation of three bands around 530, 650 and 860 nm consistent with ligand to metal charge transfer (LMCT) bands of a CoIII complex (Figure 6). In particular, bands around 800 nm have been attributed to ligand-radicals in related systems.22,29 The apparent formation of a ligand radical species paired with the lack of an observable CoIIIOO• intermediate, even at low temperatures, suggests a very rapid hydrogen atom transfer (HAT) process, possibly due to the intramolecular nature of the transfer.

Figure 6.

Figure 6.

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Air oxidation of CoII(tBu2APH)2(tBu2AP)2 (1) monitored by UV-Visible spectroscopy. Conditions: 5×10−4 M in CH2Cl2. The sample was monitored for 3 hours following the exposure to air. The first 20 min are included here.

In further support of this assignment, treatment of complex 1 with the 2,4,6-tri-tert-butylphenoxyl radical, a hydrogen atom abstraction reagent,30,31 leads to the formation of similar spectroscopic signatures, suggesting formation of a related tBu2AP radical intermediate (Figure 6). This intermediate is not stable over prolonged periods and the corresponding signals disappear when the solution is left to react under an aerobic atmosphere overnight.

Finally, the ligand radical was generated in solution, under both aerobic oxidation conditions and anerobic conditions employing the 2,4,6-tri-tert-butylphenoxyl radical, and treated with CNtBu. In both cases the corresponding 2-(tert-butylamino)benzoxazole product was formed (in 36% and 22 % yields respectively) with concomitant depletion of the signals corresponding to the ligand radical species, confirming its intermediacy in the reaction with isonitriles (Figure S18 and S19).

Coupling Reactivities of Complexes 1 and 3.

Prior to exploring the reactivities of the well-defined Co complexes in the aerobic coupling with isonitriles, tBu2APH was first confirmed to undergo efficient coupling under the standard reaction conditions. Treatment of tBu2APH with tert-butylisonitrile (CNtBu) in the presence of catalytic Co(OAc)2 in MeCN under air led to the generation of the corresponding 2-(tert-butylamino)benzoxazole in 78% yield (Scheme 6). Employing the CoII complex 1 as the catalyst led to high yields of the product (90%), while the CoIII complex 3 provided only 40% yield (Scheme 6). Given the disparity in yields, we further explored the reactivity of both complexes under stoichiometric reaction conditions.

Scheme 6.

Scheme 6.

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Cobalt-Catalyzed Oxidative Coupling of tBu2APH with tert-Butylisonitrile.

The stoichiometric competencies of complexes 1 and 3 were tested with the addition of CNtBu under both aerobic and anerobic reaction conditions (Scheme 7). In the case of CoII complex 1, no benzoxazole product was observed under a N2 atmosphere, while 61% yield was obtained when the reaction was conducted under air. These data indicate the need for an oxidant when CoII species are employed.

Scheme 7.

Scheme 7.

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Stoichiometric Control Experiments of CoII(tBu2APH)2(tBu2AP)2 (1) under Aerobic and Anaerobic Reaction Conditions.

The analogous reactions employing the CoIII complex 3 led to the formation of benzoxazole under both anaerobic (37%) and aerobic (54%) conditions, with a higher yield obtained under the latter (Scheme 8). These results suggest that CoIII is capable of mediating the oxidative cyclization in the absence of an external oxidant. The lower yield, however, may indicate an alternative reaction pathway is operative.32 Reduced yields by CoIII under N2 indicate the importance of CoII/O2 in accessing an active intermediate other than CoIII. Thus, our further studies have focused on the aerobic oxidation pathway from CoII.

Scheme 8.

Scheme 8.

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Stoichiometric Control Experiments of CoIII(tBu2AP)3 (3) under Aerobic and Anaerobic Reaction Conditions.

Product formation from complex 1 could occur directly at the bound tBuAP ligand or with the free APH through an outer-sphere pathway. To probe if product forms more readily from the bound tBuAP or free APH, the crossover experiment was conducted with the unsubstituted aminophenol under our standard oxidative cyclization conditions. Treatment of the well-defined CoII complex 1 with the parent APH and CNtBu leads to the formation of both possible coupling products resulting from coupling of free APH and ligand tBu2AP in 55% and 32% yields respectively (Figure 7). Similarly, treatment of CoIII complex 3 with APH and CNtBu also forms both possible benzoxazole products in 50% and 29% yields respectively (Figures S24 and S25).

Figure 7.

Figure 7.

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(A) 1H NMR spectra and (B) reaction time-course plot for the reaction of CoII(tBu2APH)2(tBu2AP)2 (1) with 2-aminophenol (APH) and tert-butyl isocyanide (CNtBu). Open circles (Inline graphic) indicate aminophenol, blue triangles ((Inline graphic) indicate 2-(tert-butylamino)benzoxazole; and red circles (Inline graphic) indicate 5,7-di-tert-butyl-2-(tert-butylamino)benzoxazole. Initial conditions: 2-aminophenol (0.5 mmol in 5 mL CH3CN), tert-butyl isocyanide (0.5 mmol in 5 mL CH3CN), Complex 1 (0.05 mmol in 5 mL CH3CN).

The majority of the tBu2AP ligand is converted to product. To determine if this conversion of ligand occurs more rapidly or more slowly than reaction of the free APH, the formation of the two different benzoxazole products was monitored over time by 1H NMR spectroscopy (Figure 7A). Early reaction times showed an initial burst in formation of the 5,7-di-tert-butyl-2-(tert-butylamino)benzoxazole, with saturation occurring after approximately 1 hour (Figure 7B). The formation of the unsubstituted 2-(tert-butylamino)benzoxazole derived from free APH occurred with a linear increase during the first 6 h of the reaction. These data suggest that product formation occurs more rapidly at the bound tBu2AP and that the unsubstituted APH is activated by coordination following the dissociation of product. Thus, these results support a ligand-based oxidative coupling reaction that occurs at the Co-center, and do not support an outer-sphere electron-transfer type pathway.

Overall, the data reported here support the intermediacy of an tBu2AP ligand radical that is formed from the aerobic oxidation of CoII (1). Crossover experiments of complex 1 with the parent APH indicate that the reaction occurs more rapidly at the metal center with ligated tBu2AP than with unbound APH. Coordination of O2 to 1 could generate a Co-O2• species which undergoes rapid intramolecular HAA to yield the ligand tBu2AP radical observed by EPR and UV-visible spectroscopies. The resulting ligand radical is then trapped with CNtBu to ultimately generate the benzoxazole product (Scheme 9).33

Scheme 9.

Scheme 9.

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Putative Pathway for the Formation of 2-(tert-Butylamino)benzoxazole from Complex 1 in the Presence of O2 and tert-Butylisonitrile.

CONCLUSION

In this study, we have synthesized and characterized three new cobalt complexes bearing ortho-aminophenol-derived ligands. These compounds are the first examples of well-defined cobalt complexes that bear ortho-aminophenol ligands with unsubstituted NH2 groups. Stoichiometric reactivity studies of both CoII and CoIII complexes demonstrated both species to mediate the oxidative cyclization reactions of the aminophenol ligand with CNtBu. Stoichiometric oxidation studies suggested activation of O2 by the CoII complex 1 to generate a ligand radical intermediate which is trapped by CNtBu.

These studies represent the first example of the reactivity of cobalt-aminophenol complexes in aerobic oxidation catalysis, and highlight a key role for a ligand radical in the oxidation sequence. While extensive stoichiometric studies of related cobalt-aminophenol complexes have been reported, prior systems all bear bulky substituents on the nitrogen and are not catalytically relevant. We anticipate that these new unsubstituted analogs will prove valuable to the study of other Co-catalyzed aerobic oxidation reactions.

Supplementary Material

IC1c03686 SI

ACKNOWLEDGMENT

We are grateful to the ACS PRF (56083-DNI3) and West Virginia University for financial support of this work. J.L. was supported in part by the NIH (1R15GM126514-01). NMR spectroscopy (CHE-1228336) and X-ray diffraction (CHE-1336071) facilities were partially supported by the NSF. We thank Dr. Michael Gunther for assistance with EPR data collection and Dr. Carsten Milsmann for assistance with EPR data modeling.

Footnotes

Supporting Information

The Supporting Information is available free of charge on the ACS Publications website.

Synthetic and catalytic experimental details, complete characterization data for all new compounds (PDF)

Crystallographic data for 1 (CIF)

Crystallographic data for 2 (CIF)

Crystallographic data for 3 (CIF)

The authors declare no competing financial interest.

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