pubs.acs.org/IC Article Csp2−H Amination Reactions Mediated by Metastable Pseudo‑Oh Masked Aryl-CoIII-nitrene Species Lorena Capdevila,⊥ Marc Montilla,⊥ Oriol Planas, Artur Brotons, Pedro Salvador, Vlad Martin-Diaconescu, Teodor Parella, Josep M. Luis,* and Xavi Ribas* Cite This: Inorg. Chem. 2022, 61, 14075−14085 Read Online ACCESS Metrics & More Article Recommendations * sı Supporting Information ABSTRACT: Cobalt-catalyzed C−H amination via M-nitrenoid species is spiking the interest of the research community. Understanding this process at a molecular level is a challenging task, and here we report a well-defined macrocyclic system featuring a pseudo-Oh aryl-CoIII species that reacts with aliphatic azides to effect intramolecular Csp2−N bond formation. Strikingly, a putative aryl-Co�NR nitrenoid intermediate species is formed and is rapidly trapped by a carboxylate ligand to form a carboxylate masked-nitrene, which functions as a shortcut to stabilize and guide the reaction to productive intramolecular Csp2−N bond formation. On one hand, several intermediate species featuring the Csp2−N bond formed have been isolated and structurally characterized, and the essential role of the carboxylate ligand has been proven. Complementarily, a thorough density functional theory study of the Csp2−N bond formation mechanism explains at the molecular level the key role of the carboxylate-masked nitrene species, which is essential to tame the metastability of the putative aryl-CoIII�NR nitrene species to effectively yield the Csp2−N products. The solid molecular mechanistic scheme determined for the Csp2−N bond forming reaction is fully supported by both experimental and computation complementary studies. ■ INTRODUCTION The introduction of nitrogen functionalities into organic source due to its 2e-oxidant character with concomitant extrusion of inert N2.9,18,19 The latter, together with the low- frameworks has attracted considerable interest in the develop- symmetry requirement, forces the design of low oxidation state ment of new methodologies, given their ubiquitous occurrence CoI species that form isolable CoIII-imido multiple-bonded in pharmaceuticals and natural products.1 A powerful strategy species upon reaction with N3-R.16,17 Although this chemistry to achieve the construction of C−N bonds is based on the is dominated by the use of low valent cobalt systems, few direct functionalization of C−H bonds, which has been widely examples are reported on direct Csp2−N bond formation through C−H activation involving putative high-valent Co studied in the last few decades.2−8 This field has been mainly platforms.20,21 Indeed, highly unstable octahedral high valent dominated by the use of noble metal catalysis; yet, the MV�NR species with Group 9 metals are proposed as key development of more sustainable methodologies using M- intermediate species in Csp2−N bond forming processes. nitrenoid species with first-row transition metals has recently Remarkably, their relevance has been clearly pointed out become a hot topic.9 formally in Oh MV Group 9 complexes bearing a Cp* M-Nitrenoid species are rare and unstable species for late ligand.9,22 Reaction of cyclometalated Cp*RhIII and Cp*IrIII transition metals. For Group 8 M-nitrenoids, a prominent complexes with N3-R render the proposed Cp*MV�NR example is the relatively stable octahedral iron(IV) terminal intermediate species,23,24 which are essential for the inner- imido complex [FeIV(N4Py)(NTs)]2+ reported by Que and sphere Csp2−N bond forming step with the cyclometalated co-workers,10 with S = 1 and a half-life of 3 h at room ligand (Figure 1a). Regarding the analogous cobalt chemistry temperature.11,12 For transition metals in Group 9 and beyond, bearing a Cp* ligand, Matsunaga and Kanai demonstrated the the common instability of Oh M-nitrenoid species may be overcome by changing the spin state or the geometry of the complex. In particular, the isolation of Group 9 Co-nitrene Received: June 17, 2022 species has been achieved by lowering the symmetry and Published: August 23, 2022 coordination number of the complex,13−15 highlighting four- coordinated complexes featuring tetrahedral geometry.16,17 Among all aminating reagents used to forge C−N bonds with cobalt catalysis, organic azides constitute an attractive N- © 2022 The Authors. Published by American Chemical Society https://doi.org/10.1021/acs.inorgchem.2c02111 14075 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article Figure 1. (a, b) Cp*-M-nitrenoid species proposed for the C−H amination reactions (M = Ir, Rh, Co); (c) this work. ability of Cp*CoIII catalysts to perform the Csp2−H amidation catalytic formation of the final Csp2−C products.30,31 Because of indoles using sulfonyl azides and phosphoryl azides.25,26 The of the extra stabilization offered by these model platforms, we Csp2−H amidation of indoles using acyl azides has also been hypothesized that they could offer a suitable electronic and reported using Cp*CoIII by Punniyamurthy and co-workers geometric environment for studying the reactivity of pseudo- (Figure 1b)27 and using phenyl azidoformates by Chang and Oh aryl-CoIII organometallic complexes toward organic azides. co-workers.28 Also, isoquinolone synthesis via Cp*CoV Herein, we report the N atom transfer reactivity of organic cobaltacycles using N-chloroamides was reported by Zhu and azides with well-defined aryl-CoIII complexes (Figure 1c), co-workers.29 Despite these incipient reports, the high valent focusing on the step-by-step reactivity of intermediate species approach in Co-catalyzed Csp2−H amination is still in its to unravel key mechanistic details of the Csp2−N bond infancy. formation. Aliphatic azides were found to efficiently effect the The examination of structure and electronic properties of Csp2−N bond products. With a combination of experimental key intermediate species is foremost for unveiling the and density functional theory (DFT) studies, the full mechanistic intricacies of inner-sphere N atom transfer reconstruction of the N atom transfer process was revealed. chemistry. To this end, our group has been interested in the Several intermediate species featuring the Csp2−N bond elucidation of transient intermediates involved in several Csp2− formed have been isolated and structurally characterized. H functionalization reactions. In 2016, we reported a set of The essential role of carboxylate-masked nitrenoid species to aryl-CoIII complexes synthesized through Csp2−H activation tame the metastability of the putative Co-nitrenoid was which were catalytically competent in alkyne and diazoacetate confirmed both experimentally and theoretically, affording a annulation reactions.30−34 Thanks to the stability offered by solid mechanistic picture of the Csp2-N bond forming process. the 12-membered macrocyclic model substrate employed, we The Co-nitrenoid is clearly described as an pseudo-Oh aryl- were able to isolate an unprecedented C-metalated cis-aryl- CoIII-nitrene based on molecular orbital and electron density CoIII-alkyl enolate complex, i.e., a masked-carbene species, analyses, in contrast to the previously reported Oh Cp*CoV� which was demonstrated to be an on-cycle intermediate in the NR imido species (Figure 1a,b).25,26 14076 https://doi.org/10.1021/acs.inorgchem.2c02111 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article Scheme 1. Reactivity of the Aryl-CoIII (1-OAc) with Organic Azides to Afford Complexes 2x-OAc and 3x-OAca a NMR yields of 3x-OAc are based on 2x-OAc. Selected bond distances for [Å] and angles [deg]: C(19)−N(27) 1.441(16), N(27)−Co(1) 2.009(11), C(19)−N(27)−Co(1) 110.3(9), Co(1)−O(5) 1.924(9), Co(1)−N(16) 1.955(12), Co(1)−O(3) 1.932(9), Co(1)−O(4) 1.930 (9). Hydrogen atoms, anions, and solvents molecules have been omitted for clarity. ■ RESULTS AND DISCUSSION The reactivity of the well-defined aryl-CoIII complex (1-OAc) OAc crude mixture to H2O or O2 clearly suggested that the origin of the hydroxo groups in 3a-OAc is O2. with organic azides as nitrene precursors started by examining Encouraged by these results, we explored the reactivity of 1- its reaction with p-NO2-phenyl azide. Unfortunately, the use of OAc with (2-azidoethyl)benzene (b) and (3-azidopropyl)- aromatic azides led to decomposition and formation of benzene (c) (Scheme 1). Using an excess of the azide b and c unidentified products. On the other hand, positive results (6 equiv), the corresponding inserted complex (2b-OAc and were obtained with aliphatic azides. We started with the 2c-OAc) was obtained in 26% and 25% yield, respectively. addition of benzyl azide (a) to 1-OAc complex using Both complexes led to the quantitative formation of the fluorinated alcohols as solvent (TFE or HFIP) at 50 °C, corresponding dimer 3b-OAc and 3c-OAc, analogous to affording the aryl-amine coupling complex 2a-OAc in 46% complex 3a-OAc (vide supra). yield (Scheme 2). This complex was structurally characterized The better yields observed for 2a-OAc after treatment of 1- by 2D NMR studies, where a diagnostic HMBC peak between OAc with benzyl azide prompted us to scrutinize the the benzylic −CH2 of the formal azide and the quaternary demetalation step. On the basis of previous reports,24 the carbon of the aryl moiety was observed, proving the formation protodemetalation step to render the aminated product was of a new Csp2-NH bond. The coordinatively saturated complex predicted to be kinetically and thermodynamically disfavored. 2a-OAc slowly evolved at room temperature to a more stable Thus, to favor this step, we designed alternative strategies dinuclear species, 3a-OAc, in quantitative yield (see 1H NMR based on the use of strong acids and thermolysis (Scheme 2). time-evolution in Figure S1). Crystals of 3a-OAc were First, HCl (2 M) was added to a solution of 2a-OAc in CHCl3, obtained from slow evaporation from a CH2Cl2 solution and after 16 h the crude mixture was basified and extracted, (DCM/pentane) at −4 °C, allowing for an unambiguous affording the aminated product P-a in 44% isolated yield. The characterization of this dimeric species. Compound 3a-OAc analogous reaction using 2b-OAc and 2c-OAc afforded the features the new Csp2−NH bond, and each CoIII center corresponding aminated product P-b and P-c in 40% and 42% presents a distorted octahedral geometry, with coordination to respectively. On the other hand, heating 2a-OAc to 100 °C in Npy, NHL, and NHazide as well as one OAc and two μ-hydroxo HFIP furnished the cyclized product P-a-cyc in 27% yield. The bridging ligands. Independent blank experiments exposing 2a- analogous cyclic products using 2b-OAc and 2c-OAc were not 14077 https://doi.org/10.1021/acs.inorgchem.2c02111 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article Scheme 2. Thermal Decomposition and Acidic Work-up Affording the Corresponding Aminated Product P-a, P-b, P-c, and P- a-cyca a Isolated yields shown. formed under the same conditions, which highlights the The use of EWG and EDG substituents did not affect the importance of the benzylic position for the formation of formation of the inserted 2a-OBz-X complex (Scheme S9). cyclized product (see mechanistic proposal for P-a-cyc Subjecting the mixture to acidic conditions led the formation formation in Scheme S7). of P-a product in similar yields. Moreover, the direct formation The absence of an analogous cyclic product from 2b-OAc of P-a-cyc product was achieved by reacting several 1-(OBz-X) and 2c-OAc led us to investigate in depth the reactivity of with benzyl azide (a) under thermal conditions. The most these azides under different thermal conditions (Scheme 3). coordinating p-OMe-benzoate affords a 42% yield, whereas the When 1-OAc was mixed with an excess of azide b at 100 °C in least coordinating p-NO2-benzoate affords only 16% yield, thus TFE, a new paramagnetic species appeared and was stable following the expected trend (see Scheme S11). However, the under inert atmosphere. XRD analysis showed a CoII complex coordinating p-Me-benzoate drops to 17%, and the p-Cl- with distorted octahedral geometry bearing the phenylethan-1- benzoate affords 49%. Therefore, the use of EWG and EDG amine moiety inserted (4b-OAc), which under acid conditions substituents did not affect the formation of either complex 2a- forms the product P-b in 41% NMR yield with respect to the OBz-X complex or the final organic product P-a-cyc. 4b-OAc complex. Mechanistic Investigations. To gain more mechanistic Moreover, X-ray absorption spectroscopy (XAS) was insights of the Csp2−N bond formation, additional tests were conducted for 4b-OAc, clearly confirming the CoII oxidation performed. By adding TEMPO radical at 50 °C, MS peaks state for the metal center (Table S2, Figure S22, Panels S1− matching with a CoII complex bearing the formed Csp2−N S3) compared to CoIII species 1-OAc and the newly bond were detected, whereas at 100 °C the yield of P-a-cyc synthesized aryl-CoIII-benzylamine complex (5-OAc, see dropped from 27% to 7%. These results are not conclusive for Scheme S13). The Co-ligand bond distances in the crystal either a radical or nonradical pathway since Csp2−N coupling is structure of 4b-OAc (>2.1 Å) suggest a high spin CoII−d7 occurring, although in lower yields. Therefore, on the basis of electronic configuration, which was supported by the μeff all experimental evidence, a thorough computational DFT calculated using Evans method in CD2Cl2. The obtained study was mandatory to unravel the precise mechanism for the value of μeff = 4.22 MB is in agreement with the presence of intriguing Csp2−N bond forming step using benzyl azide and 1- three unpaired electrons. We hypothesized that the CoII OAc (Figure 2 and Figure 3). The calculations were performed complex 4b-OAc stemmed from reductive elimination of an at the revTPSS-D3BJ/Def2TZVP//BP86-D3BJ/Def2SVP in situ aryl-CoIV-imido, although more investigations are level of theory (see Supporting Information for full computa- needed to shed some light on the detailed mechanism of the tional details and benchmark study). The rate-determining step formation of 4b-OAc. of the reaction corresponds to the N2 extrusion from 1-OAc· The nature of the carboxylate ligand was also investigated, N3Bz to yield the short-lived species INT-N. Wave function and we prepared the analogous 1-(OOCR) complex bearing a analysis of INT-N indicated without a doubt that INT-N is substituted benzoate instead of the initial acetate (see Figures best described as an aryl-CoIII�N-R (R = −CH2Ph) nitrene S23−S24 for the XRD of 1-(OBz-CF3) and 1-(OBz-OMe)). species (Fischer-type) with σ and π bonds between the Co and 14078 https://doi.org/10.1021/acs.inorgchem.2c02111 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article Scheme 3. (A) Reactivity of Aryl-CoIII (1-OAc) with Organic Azide (b) at 100 °Ca and (B) Crystal Structure of 4b-OAc Complexb a NMR yield of P-b is based on 4b-OAc. bSelected bond distances for [Å] and angles [deg]: C(12)−N(20) 1.439(5), N(20)−Co(1) 2.176(4), C(12)−N(20)−Co(1) 109.7(2), Co(1)−N(18) 2.127(4), Co(1)−N(9) 2.259(4), Co(1)−N(2) 2.255(4), Co(1)−O(33) 2.075(3), Co(1)− O(29) 2.056(3). Hydrogen atoms and solvent molecules have been omitted for clarity. NH(L) refers to the coordination of the Co(II) center to another ligand moiety (depicted as N9 in the crystal structure). the N atoms (bond order of 1.51 and bond length of 1.71 Å). with a Co−N bond length of 1.73 Å. As it can be seen by the Effective oxidation state (EOS) analysis in INT-N dissects the occupation and shape of the effective fragment orbitals (EFOs) N−Co σ and π bonds into two contributions from the ligand depicted in Figure S36, in the singlet−triplet transition, the S = and the metal, as shown in Figure 2 (see also Supporting 0 beta electron of the lone-pair of the N is transferred to a p- Information). Considering the corresponding occupations of type EFO of the N, resulting in a triplet state with two alpha p- the effective fragment orbitals (EFOs), the EOS analysis type nonbonding electrons on the N. In addition, the assigns the two electrons of the N−Co σ bond to the nitrene, remaining two beta electrons form two Co−N one-electron whereas the two electrons of the N−Co π bond are assigned to π bonds polarized toward the Co (see Figure S37). This the Co. Therefore, INT-N may be described as an aryl CoIII- analysis agrees with the fact that the major contribution of the nitrene with significant back-donation from Co to N. spin density (i.e., electron density of alpha electrons minus the Qualitative analysis of the relative contributions of N and Co electron density of the beta electrons, which indicates the to the π and π* canonic molecular orbitals also characterize localization of the unpaired electrons) of the S = 1 state of INT-N as a aryl CoIII-nitrene (Figure S33 and Table S10), INT-N is localized in the N (see Figure S34 and Table S12) ruling out an aryl-CoV-imido species (Schrock-type).35 and that the singlet → triplet spin-crossing does not cause The EOS analysis of the S = 1 spin state of INT-N indicates significant change in the Co−N bond distance or in the formal that the triplet INT-N can also be described as a CoIII-nitrene oxidation state of the Co. 14079 https://doi.org/10.1021/acs.inorgchem.2c02111 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article intermediate INT-N, for which the triplet state is only 0.5 kcal/mol more stable than the singlet. However, because of the important electron reorganization that takes places on the N in the singlet−triplet transition, the probability of a spin-crossing between the singlet and the triplet Gibbs energy surfaces is strongly reduced. Thus, all of the computational evidence indicates that the reaction profile undergoes a singlet species. We have performed several DFT relaxed PES scans to explore the stability of aryl-CoIII-nitrene complex INT-N upon distortion or disconnection of one of the coordinating N.17 However, all of the calculations confirm that the tight coordination environment imposed by the macrocyclic ligand in the aryl-CoIII-nitrene complex INT-N is mandatory for its stabilization. In addition, we have tried to locate the transition state that corresponds to the direct formation of the C−N bond (species 2a) from intermediate INT-N. However, all of our attempts lead to transition state TS2 or intermediate INT- MaskN. The role of carboxylate anions was experimentally confirmed by using the acetate-free organometallic [aryl-Co III - (CH3CN)2]2+ complex (1-CH3CN) (Scheme S14). Applying reaction conditions at 50 and 100 °C using benzyl azide (a), neither the aryl-amine coupling complex (analogous to 2a- OAc) (50 °C) nor final organic product P-a-cyc (100 °C) was Figure 2. Effective fragment orbitals (EFOs) graphical representation detected. Furthermore, the presence of benzylaldehyde as a and occupations�in the [0,1] range�associated with the σ (top) side product suggested the degradation of benzyl azide, and π (bottom) interaction between the PhCH2N ligand and the Co pointing out the importance of the formation of the masked- center. aryl-Co-nitrene species INT-MaskN toward the Csp2−N coupling. This intermediate species rapidly evolves overcoming a very Previously, some of us studied the mechanism of Csp2−H low barrier (<2 kcal/mol, TS2) to a 14 kcal/mol more stable functionalization with diazo esters catalyzed with a aryl-CoIII- INT-MaskN species by formation of a five-member acetoxy- carboxylate compound,31 in which the key role of a (benzyl)amide ring via carboxylate attack to the N atom, carboxylate-masked aryl-CoIII-carbene was proven. Analo- formally defined as a masked aryl-Co-nitrene. Wave function gously, the formation of the aryl-Co-nitrene, the facile analysis describes INT-MaskN as a masked CoIII nitrene with a evolution of the nitrene through a low-lying transition state single σ bond between the Co and the N. The lack of a Co�N to form a five-member acetoxy(benzyl)amide ring, as well as π bond is also evidenced by the increased bond distance of the final SN2-type substitution of the aryl-Co to the masked 1.91 Å (1.71 Å for INT-N) and a decreased bond order of nitrene are reminiscent of the mechanism of the cobalt- 0.78. catalyzed Csp2-H functionalization with diazo esters. The key The masked aryl-CoIII-nitrene (or “nitrenoid”)36 is not difference between both mechanisms is the stability of the sufficiently stabilized to be experimentally trapped since it masked carbene and the masked nitrene. Whereas the masked- allows the formal nucleophilic attack of the aryl moiety to the carbene could be isolated and fully experimentally charac- N atom of the masked nitrene to finally achieve the Csp2−N terized because the final nucleophilic attack is the rate- coupling through a barrier lower than 9 kcal/mol, TS3. The determining step of the reaction, the analogous masked nitrene partial atomic charge of the N atom in INT-MaskN (−0.51) vs could not be isolated due to the barrier to form the coupling INT-N (−0.74) explains the enhanced electrophilic character product being much smaller than the barrier for the formation of the former, induced by the formation of the acetoxy- of the aryl-CoIII-nitrene. Experimentally, we conducted UV− (benzyl)amide. Moreover, EOS analysis also reveals a larger vis monitoring analyses at variable temperature, which allows occupation of the aryl sigma contribution in INT-MaskN us to determine that the release of N2 toward the formation of compared to INT-N, which favors the SN2 attack, and is an the nitrene species INT-N is indeed the rate-determining step indication of the enhanced nucleophilic character of the aryl in (rds) of the reaction (ΔG‡ = 23.9 kcal/mol, Eyring plot in INT-MaskN (see Figure S32). Figure S20), which nicely agrees with the DFT Gibbs energy The reaction profile has also been evaluated for S = 2 and S profile of the reaction mechanism presented in Figure 3. MS = 1 spin states. The energies of the S = 2 state of all analysis after mixing time agrees with the accumulation of 1- intermediates and transition states involved in the reaction OAc·N3Bz species (Figures S19 and S20). mechanism are far higher than the singlet, and therefore the The proposed general mechanism is shown in Scheme 4. quintuplet states play no role in the studied reaction This study demonstrates the stabilizing masking effect of the mechanism (see Table S11). The triplet states does not play carboxylate group to the Co-nitrene moiety, to tame the a key role either. The S = 1 state of the initial complex extraordinary reactivity and elusiveness of Co-nitrene species. interacting with the benzyl azide is 22.1 kcal/mol above the Intermolecular Nitrene-Transfer Attempts. Addition- singlet (Figure 3). The Gibbs energy of S = 1 states for TS1, ally, nitrene transfer was attempted by adding xanthene (2 TS2, INT-MaskN, TS3, and 2a are also clearly higher than equiv) to the mixture of 1-OAc and benzyl azide (a), but no their S = 0 counterparts. The only exception is Co-nitrene intermolecular Csp2−N coupling product with xanthene was 14080 https://doi.org/10.1021/acs.inorgchem.2c02111 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article Figure 3. RevTPSS-D3BJ/Def2TZVP//BP86-D3BJ/Def2SVP free energy profile for the studied reaction mechanism. Gibbs free energies (G, in kcal·mol−1) are relative to 1-OAc·N3Bz. The pathway in black corresponds to the singlet species (S = 0), while the blue pathway corresponds to the triplet species (S = 1). Geometries for all S = 0 intermediates and transition states are shown (nitrogen atoms are represented in blue, oxygens in red, cobalt in orange, carbon in white, and hydrogens in gray. Note that hydrogens bonded to carbon have been hidden for clarity). Relevant distances have also been included (in Å). Scheme 4. Proposed Mechanism for the Reaction of 1-OAc with Benzylazide (a) 14081 https://doi.org/10.1021/acs.inorgchem.2c02111 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article detected, and intramolecular 2a-OAc (20%) was formed (see of other transition metal masked nitrene species (Ru) is also Scheme S15). proposed in chiral α-amino acid synthesis using carbamate Comparing the Reactivity of Organometallic CoIII and derivatives.38 Interestingly, this in situ masking strategy is a RhIII Complexes. To gain more insight into the mechanism, straightforward alternative to the use of stabilized nitrene we explored the reactivity of benzyl azide using an analogous sources such as dioxazolones (CO2-evolving reagent), which aryl-RhIII complex. However, attempts to isolate the aryl-RhIII focus the scope on amidation reactions.39−41 analogous to 1-OAc using L-H were unsuccessful. Thus, we attempted the formation of P-a-cyc by reacting the L-H ligand with benzyl azide (a) and stoichiometric amounts of ■ EXPERIMENTAL SECTION Formation of 2x-OAc and 3x-OAc Complexes. 1-OAc (0.048 Rh(OAc)3 in TFE at 100 °C. In contrast to the aryl-CoIII mmol) and organic azides (a−c) with 1 mL of HFIP were mixed in a complex, P-a-cyc cyclic product was not formed, and we only 2 mL vial and sealed. The mixture was heated at 50 °C overnight. detected the formation of hydrazine. Therefore, since the aryl- Then, the crude mixture was concentrated under a vacuum line until RhIII complex was not isolable with L-H, we attempted the initial volume was reduced to two-thirds observing the formation successfully the comparison of both aryl-CoIII (1Me-OAc) and of 2x-OAc intermediate complex by 1H NMR (CDCl3) and HRMS. aryl-RhIII (6Me-OAc) synthesized with the L-Me ligand. CoIII The corresponding dimeric species 3x-OAc were slowly formed by complex 1Me-OAc was mixed with benzylazide, but no reaction recrystallization with CHCl3 layered with pentane under air. Synthesis of P-x Products. Once the 2x-OAc were formed, each was observed. By reacting complex 6Me-OAc with benzylazide, crude mixture was dissolved in CHCl3, and HCl (3 mmol, 2 M) was only aryl-RhIII-imine species (7xMe-OAc) was observed, with added and stirred overnight. The crude was basified until pH 14 and no trace of Csp2-N bond-formed species (Scheme S18). The extracted with CHCl3. The products were purified by column contrasting reactivity of Co versus Rh analogues highlights the chromatography using neutral alumina (CHCl3, then CHCl3/MeOH uniqueness of Co reactivity, its versatility to stabilize 8:2), giving the corresponding Csp2−N coupling products (P-a, P-b, metastable species via carboxylate masking, and the value of and P-c). studying in depth the role of first row metals in C−N Synthesis of P-a-cyc Product. 1-OAc (0.048 mmol) and benzyl formation. azide (a) (2.1 equiv) were mixed in HFIP (1 mL) in a 2 mL vial and sealed. The crude was heated at 100 °C overnight in the absence of ■ CONCLUSIONS In summary, we have studied the reactivity of well-defined light. The solvent was then removed, and the cyclic product was purified by column chromatography using neutral alumina (CHCl3, then CHCl3/MeOH. 8:2). pseudo-Oh aryl-CoIII species (1-OAc) with different azides, Formation of 4b-OAc. 1-OAc (0.048 mmol) and (2-azidoethyl)- with successful intramolecular Csp2−N bond formation with benzene (b) (6.0 equiv) were mixed in TFE (1 mL) in a 2 mL vial aliphatic azides. In brief, when benzyl azide is used, we are able and sealed. The crude was heated at 100 °C, and after 16 h the to trap the just-formed Csp2−N bond species, consisting of a solvent was removed. Pentane diffusion in a concentrated solution of CH2Cl2 anhydrous under inert atmosphere yields the 4b-OAc CoIII complex (2a-OAc) that tends to dimerize to form complex. complex 3a-OAc. Analogous reactivity is found for (2- Computational Details. All DFT calculations were carried out azidoethyl)benzene (b) and (3-azidopropyl)benzene (c). using Gaussian16 program. Geometry optimizations have been However, only 2a-OAc evolves to an intramolecular cyclization performed without any symmetry restrictions, considering the effect to obtain the organic product P-a-cyc, whereas 1-OAc reacts of the HFIP solvent via the Self-Consistent Reaction Field method with b under thermal treatment to afford a well-defined CoII using the SMD solvation model42 and taking into account dispersion complex featuring the already formed Csp2−N bond (4b-OAc). effects with Grimme and co-workers DFT-D3BJ correction,43,44 at the The thorough DFT study performed demonstrates the BP86-D3BJ(SMD)/Def2SVP level of theory.45−48 The HFIP solvent stabilizing masking effect of the carboxylate group to tame is not implemented in GAUSSIAN16, so we performed those calculations using the Solvent = Generic,Read options for the SCRF the extraordinary reactivity and elusiveness of an aryl-CoIII� keyword (see Supporting Information for further details). All N-R nitrene species (INT-N). First, the Gibbs energy barrier geometry optimized structures were characterized by analytical of the rate-determining step of the reaction, which corresponds frequency calculations, which also afforded enthalpy and entropy to the N2 extrusion, is in agreement with the Gibbs energy corrections at 298.15 K. All points in the reaction pathway were barrier extracted from the Eyring plot and the mild connected via IRC calculations. Single point calculations on the experimental conditions applied (50 °C). More importantly, equilibrium geometries, including the solvent and dispersion effects detailed wave function analysis of the masked aryl-CoIII-nitrene (Esp), were carried out at the revTPSS-D3BJ(SMD)/Def2TZVP level species INT-MaskN clearly shows an increase of electro- of theory.49 Then, the total Gibbs energy values (G) are given by philicity on N and an increase of nucleophilicity on the Csp2- G = Esp + Gcorr + G° / * (1) aryl compared to INT-N, thus promoting the facile SN2-like attack to effect the Csp2−N coupling. This is in line with the where the Gibbs energy correction (Gcorr.) was obtained from the fact that the SN2-like barrier is far lower than the barrier for the thermodynamical analysis at the optimization level of theory but formation of the aryl-CoIII-nitrene and with the fact that these corrected using the GoodVibes code50 so that frequencies below 100 masked species could not be trapped as in the case of the are not treated with the Harmonic Approximation, but rather with the masked carbene.31 The key role of carboxylate anions in the Quasi-Harmonic Approximation as described by Grimme.51 Finally, formation of masked aryl-CoIII-nitrene species, fully supported the additional correction term ΔG°/* accounts for the transition from by both experimental and computation studies, culminated in a the standard state concentration (gas phase, pressure of 1 atm) to the solid mechanistic picture of the Csp2−N bond forming concentrations used experimentally. Metal and ligands oxidation states (OS) were assigned with the amination process, which is thought to be valuable for the effective oxidation states (EOS) analysis, which relies on Mayer’s future development of catalytic Csp2−N methodologies via effective fragment orbitals (EFOs) and their occupations. The EFOs Co�NR species. Indeed, CoIII masked nitrene species have are sorted by decreasing occupation number, and individual electrons been crystallographically isolated very recently,37 further (or pairs for closed-shell singlets) are assigned to those EFOs with supporting the validity of our study. Moreover, the occurrence higher occupations. This leads to an effective configuration of the 14082 https://doi.org/10.1021/acs.inorgchem.2c02111 Inorg. Chem. 2022, 61, 14075−14085 Inorganic Chemistry pubs.acs.org/IC Article atoms/ligands within the molecule, which directly determines their Teodor Parella − Servei de RMN, Facultat de Ciències, OS. EOS analysis was performed at the revTPSS-D3BJ/Def2TZVP Universitat Autònoma de Barcelona, Bellaterra E-08193 level of theory with the in-house developed program APOST-3D,52 Catalonia, Spain; orcid.org/0000-0002-1914-2709 using the Topological Fuzzy Voronoi Cells (TFVC) atomic definition and a 40 × 146 atomic grid for the required numerical integrations. Complete contact information is available at: https://pubs.acs.org/10.1021/acs.inorgchem.2c02111 ■ * ASSOCIATED CONTENT sı Supporting Information Author Contributions ⊥ The Supporting Information is available free of charge at L.C. and M.M. contributed equally. https://pubs.acs.org/doi/10.1021/acs.inorgchem.2c02111. Notes Additional experimental details, materials, instrumenta- The authors declare no competing financial interest. tion, spectroscopic characterization of all compounds, computational details and X-ray crystallography details of 1-OBzCF3 (CCDC 2097542), 1-OBzOMe (CCDC ■ ACKNOWLEDGMENTS This work was financially supported by MICINN (CTQ2016- 2097543), 3a-OAc (CCDC 2097546), 4b-OAc (CCDC 77989-P and PID2019-104498GB-I00 to X.R., PGC2018- 2097544), and 5-OAc (CCDC 2097545) (PDF) 098212-B-C22 to J.M.L. and PGC2018-095808-B-I00 to T.P.) and Generalitat de Catalunya (2017SGR264 to X.R. and Accession Codes 2017SGR39 to J.M.L.). X.R. is thankful for an ICREA CCDC 2097542−2097546 contain the supplementary crys- Academia award. X-ray absorption experiments were per- tallographic data for this paper. These data can be obtained formed at the CLAESS beamline at ALBA Synchrotron with free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by the collaboration of ALBA staff (V.M.-D.) as part of the in- emailing data_request@ccdc.cam.ac.uk, or by contacting The house experiment 2019093969. We thank Dr. A. Company for Cambridge Crystallographic Data Centre, 12 Union Road, fruitful discussions and STR-UdG for technical support. Cambridge CB2 1EZ, UK; fax: +44 1223 336033. ■ AUTHOR INFORMATION Corresponding Authors ■ REFERENCES (1) Hili, R.; Yudin, A. K. Making carbon-nitrogen bonds in biological and chemical synthesis. Nat. Chem. Biol. 2006, 2, 284−287. Josep M. Luis − Institut de Química Computacional i Catàlisi (2) Davies, H. M. L.; Long, M. S. Recent Advances in Catalytic (IQCC) and Departament de Química, Universitat de Intramolecular C-H Aminations. Angew. Chem., Int. Ed. 2005, 44, Girona, Campus Montilivi, Girona E-17003 Catalonia, 3518−3520. 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