A theoretical study of dirhodium-catalyzed intramolecular aliphatic C–H bond amination of aryl azides

Huiying Xu, Xuepeng Zhang, Zhuofeng Ke* and Cunyuan Zhao*
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, P. R. China. E-mail: kezhf3@mail.sysu.edu.cn; ceszhcy@mail.sysu.edu.cn; Fax: +86 20 8411 0523; Tel: +86 20 8411 0523

Received 18th November 2015 , Accepted 10th March 2016

First published on 11th March 2016


Dirhodium-contained catalysts mediated aliphatic C–H bond amination of aryl azides were studied using BPW91 functional. Calculations show the reactions with Rh2(esp)2 (esp = α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid) and the model compound Rh2(OCHO)4 as catalysts take place via similar mechanisms. Firstly, the dirhodium metal complex coordinates with the substrate and releases nitrogen gas. This rate-determining step results in the formation of the metal nitrene. Metal nitrene mediated intramolecular C–H bond amination is conducted via two alternative pathways, respectively. The singlet metal nitrene mediated intramolecular C–H bond amination occurs via a concerted and asynchronous pathway involving direct metal nitrene insertion into the C–H bond. The triplet metal nitrene case is a stepwise pathway involving a hydrogen transfer and then a diradical recombination. Our study suggests the triplet H-abstraction is more favorable than the singlet one. The resulted triplet intermediate would not go through the high-barrier diradical recombination process, but across to the singlet pathway via a MECP and form the final singlet product. The tethered esp ligands in Rh2(esp)2 provide steric effects to constrain the substrate-catalyst compound but indicates inconspicuous influence on the mechanisms of dirhodium catalyzed aliphatic C–H bond amination of aryl azides.

1. Introduction

C–H functionalization is an efficient approach to obtain natural or unnatural heteroatom-containing compound such as C–N bond formation among which metal nitrene mediated amination and aziridination have both attracted much attention.1–3 Nitrogen containing compound are widely used in drug synthesis because nitrogen generally exhibits ability to act as a hydrogen bond donor and/or acceptor which influences the interaction between the medicinal agent and its target significantly.4 Metal nitrene catalyzed reaction can initiate amination to form C–N bond directly.5–9 Rhodium metal compounds are one of the effective and widely used catalysts to mediate C–H bond amination.10–13 For the C–N bond formation reaction from rhodium nitrene, concerted insertion via a singlet nitrene and radical recombination via a triplet nitrene are alternative pathways.14 Du Bois and co-workers have done many researches on dirhodium catalysts and found some of them, including Rh2(OAc)4 and Rh2(esp)2, exhibit the catalysis with a concerted but asynchronous mechanism, just like Rh-catalyzed carbene insertion.15,16 Our group and co-workers also reported the intramolecular amidation of carbamates prefers the singlet pathway rather than the triplet pathway according to the free energy of activation.17 And recently we have published further study on dirhodium mediated C–H bond amination mechanism and found the reaction takes place via triplet mechanism.18,19 However, the mechanisms of rhodium-catalyzed amination would be system-dependent and thus detailed explorations on various reactions should be paid attention to.

Recently, Du Bois and co-workers2,8,12,13,20–22 designed and synthesized a new catalyst Rh2(esp)2, a tethered dicarboxylate-derived complex for intramolecular C–H oxidation and this catalyst performed excellent C–H amination with low catalyst loading.23,24 The chelating dicarboxylate ligand groups are resistant to ligand exchange and would shroud the dirhodium core even in oxidative conditions.20 Therefore, the unusual kinetic stability override other dirhodium tetracarboxylate complexes possibly has contributed to the high-efficiency of Rh2(esp)2.25 Though the use of Rh2(esp)2 could be converting C–H bond into C–N bond via amination effectively, the condensation between the substrate and terminal oxidant is obviously limited for product purifying.15 The C–H oxidation (sulfamate, carbamate, sulfamide and guanidine, etc.) mediated by rhodium catalysts usually occur under oxidative conditions and require strong electron-withdrawing groups on the nitrene.5 These limitations are not favored for expanding the scale of potential substrates and the utility of the catalytic reaction. Recently, a new type of reactions with azides has been used for the synthesis of nitrogen heterocycles via intramolecular addition.26,27 Reactions with azides involve no oxidants and would release the only byproduct N2 gas which is environmentally friendly.28–32 Driver and co-workers have reported the preparation of indoles and carbazoles that involves the catalytic decomposition of aryl azides followed by sp2 C–H bond amination reactions.33–38 On the basis of the sp2 C–H bond amination reactions, Driver and co-workers reported a new type of reactions catalyzed by Rh2(esp)2 using aryl azides as the N-atom source and it has a high conversion up to 99% (see Scheme 1).39 These reactions could occur with aryl azides containing para-electron-releasing, -neutral, or -withdrawing groups rather than require an electron-withdrawing group on the nitrogen. Rh2(esp)2 is an unusual dirhodium catalyst that is clear of rapid carboxylate ligand exchange, namely, it exhibits high kinetic stability in reaction solution.25 In the metal catalyzed C–N bond formation with aryl azides, N2 gas will be firstly released to form metal nitrene complex which undergoes subsequent nitrene transfer/insertion reaction.40–42 According to the related experiments, the diastereoisomers of products (dr 50[thin space (1/6-em)]:[thin space (1/6-em)]50) and intramolecular kinetic isotope effect (KIE) of 6.7 corroborate a stepwise C–H bond amination and the rate-determining step is the extrusion of N2.39 Therefore, it is necessary to further analyze and understand Rh2(esp)2 mediated C–H bond amination reactions. In this paper, we report a density functional theory (DFT) computational study of the mechanisms of this dirhodium catalyzed intramolecular aliphatic C–H bond amination of aryl azides. Also, the catalysis nature differences or similarities between Rh2(esp)2 (I in Fig. 1) and other dirhodium catalysts with bridging tetracarboxylate ligand groups (Rh2L4) will be discussed.

image file: c5ra24340h-s1.tif
Scheme 1 Rh2(esp)2-catalyzed intramolecular aliphatic C–H Bond amination with aryl azides. Yield as isolated after silica gel chromatography: I1 84%.39

image file: c5ra24340h-f1.tif
Fig. 1 Catalysts in the calculations of the intramolecular C–H bond amination with aryl azides: I = Rh2(esp)2, II = Rh2(OCHO)4.

2. Computational details

Theoretical calculations were performed utilizing Gaussian 09 program.43 All geometries are fully optimized using DFT method BPW91 with the 6-31G(d) basis sets for C, H, O and N atoms while the 1997 Stuttgart relativistic small-core effective core-potential [Stuttgart RSC 1997 ECP]44,45 for Rh atoms, augmented with a 4f-function (ζf(Rh) = 1.350),46 which are donated as BPW91/BS1. BPW91 is a reliable method for metal nitrene mediated reactions, especially in describing the singlet–triplet energy difference (Est) of dirhodium–nitrene complexes.17–19,47–49 Intrinsic reaction coordinate (IRC)50 calculations were done to confirm the reactant and product connecting the corresponding transition states. The energies were calculated at 393.15 K and 1 atm according to the experiment conditions.39 Natural bond orbital (NBO) analysis51,52 and Kohn–Sham frontier orbital analysis were done with the calculated level BPW91/BS1. Solvent effects (in toluene) were estimated using the polarizable continuum model (PCM) with radii and non-electrostatic terms for Truhlar and coworkers' SMD solvation model53 with a larger basis set 6-311++G(d,p) for C, H, O and N atoms and the same Stuttgart basis sets as BS1 (RSCf) for Rh atoms, which are donated as BS2. Minimum energy crossing points (MECPs) were located utilizing the MECP program developed by Harvey and co-workers.54

In order to obtain accurate thermochemistry predictions and descriptions of weak interaction, we performed geometry optimization and energy calculations of selected important intermediates and transition states at the M06L (the pure functional of Truhlar and Zhao)/BS1 level of theory.18,55 Also, the composite basis sets (denoted as BS3) consisting of the basis set 6-311G(d,p) for C, H, O and N atoms and the same Stuttgart basis sets as BS1 for Rh atoms were also employed. These calculations have shown that the BPW91/BS1, M06L/BS1 and BPW91/BS3 optimized geometries are very close, while relative energies can vary by a few kcal mol−1 with solvent effects at BPW91/BS2 or M06L/BS2 included (see ESI), and they give the same conclusions. Therefore, below, in sake of consistency, we discuss the BPW91/BS1 calculated results unless otherwise specified.

3. Results and discussions

Based on the survey of catalysts in the related experiments, the reaction yields in the presence of Rh2(esp)2, Rh2(OAc)4, Rh2(O2CC7H15)4 and Rh2(O2CC3F7)4 are 75%, 0%, 35% and 20%, respectively.39 As reported in previous literature, the tetracarboxylate ligand groups are sensitive to ligand exchange which would inhibit the cycled catalysis of C–H bond amination.5,25 However, this ligand exchange event is assumed to be inoperative in order to explore other factors that influence catalytic reactivity and reaction mechanism. To investigate the mechanistic similarities and differences between Rh2(esp)2 (I in Fig. 1) and the general dirhodium catalysts with bridging tetracarboxylate ligand (Rh2L4), in this paper, a model compound Rh2(OCHO)4 (II in Fig. 1) was used to model Rh2L4. Fig. 1 shows the computed geometries of the catalysts I and II. Comparing the key bond lengths such as Rh–Rh and Rh–O bond distances in I and II, they have almost the same values, which indicates these two catalysts have a similar framework and bimetallic interactions.

3.1. Proposed mechanism of dirhodium catalyzed C–H bond amination with aryl azide 1

Taking o-tert-butylaryl azide 1 in Scheme 1 as a sample substrate, Scheme 2 shows the proposed mechanisms of dirhodium complexes (Rh2Ln) promoted intramolecular aliphatic C–H bond amination with aryl azides. In Scheme 2, [Rh2] denotes the dirhodium paddlewheel catalysts. According to the investigations of related reactions mentioned above, the metal catalyst and the azides combine together via Rh–N bonding before N2 release.40 The intramolecular aliphatic C–H bond amination reaction might involve two steps (Scheme 2): (i) the first step is extrusion of nitrogen gas from the precursor complex of the metal catalyst and substrate, (ii) the second step is conversion of C–H bond into C–N bond, which might take place through singlet or triplet pathway. The concerted singlet pathway could form C–N and N–H bond spontaneously through C–H bond nitrogen insertion while the stepwise triplet pathway would go through H-abstraction followed by diradical recombination or intersystem crossing (ISC).47 Both the singlet and triplet pathways lead to the final product indolines and the catalyst is regenerated.
image file: c5ra24340h-s2.tif
Scheme 2 Proposed mechanisms of Rh2Ln promoted intramolecular aliphatic C–H bond amination with aryl azide 1.

3.2. Rh2(esp)2 catalyzed amination of aryl azide 1

As mentioned above, the purpose of this paper is to elucidate the reaction mechanism of dirhodium complex, Rh2(esp)2 and Rh2(tetracarboxylate)4 included, catalyzed amination which includes two basic steps: (i) extrusion of N2, (ii) nitrene insertion. In this section, the reaction with Rh2(esp)2 (I) as the catalyst is computed and compared with the case for Rh2(OCHO)4 (II). It should be mentioned that the computational data for Rh2(OCHO)4 are majorly presented in ESI. For clear descriptions, labels of the atoms in the active sites of reaction complexes are given in Scheme 3.
image file: c5ra24340h-s3.tif
Scheme 3 Depicted are labels of the selected atoms in the reaction complexes. O1 and O2 refer to the oxygen atoms coordinated to Rh1 and Rh2 centers, respectively.
3.2.1. Metal nitrene formation from Rh2(esp)2 and aryl azide 1. As reported in related investigations about metal nitrene catalyzed C–H bond amination with azides, coordination of the metal core could be towards either the α- or γ-nitrogen of the azides.41,56 However, the γ-coordination complex may not directly release nitrogen gas but transform into the α-coordination complex which could trigger amination reactions (see Fig. S1 in ESI).

The two rhodium centers in Rh2(esp)2 are in equal positions. As shown in Fig. 2, the centro-symmetric geometry of Rh2(esp)2 can provide four positions to recognize and bond with the substrate aryl azide molecule. In order to diminish steric effects, the aryl group and the tert-butyl group should be located near two out of the four “caves” divided by the tethered ligands. And from the structure of the catalyst-substrate binding complex in Fig. 2a, the aryl azide molecule rotates along Rh–N bond anticlockwise and forms the other three structures (Fig. 2b–d). In Fig. 2a and b, both the aryl group and the tert-butyl group are positioned over the less crowded caves. In Fig. 2c and d, either the aryl group or the tert-butyl group is over the crowded cave with a phenyl group pointing inside. On the other hand, the azide moiety (−N[double bond, length as m-dash]N[double bond, length as m-dash]N) may be repulsed by the ligand, especially for the structure in Fig. 2b.

image file: c5ra24340h-f2.tif
Fig. 2 Possible coordination modes of Rh2(esp)2 and aryl azides.

The four coordination complexes of aryl azide 1 and Rh2(esp)2 shown in Fig. 2 lead to four pathways of metal nitrene formation (see Fig. 3). Ac has almost the same energy as Aa while Ab and Ad are 2.3 and 1.7 kcal mol−1 higher in free energy than Aa, respectively. The higher free energies might be mainly ascribed to the steric repulsion between the ligand of I and the tert-butyl group or the azide moiety of 1. However, the energy differences are still acceptable and these four isomers could be interchanged with each other. Therefore, only the reaction from Aa is discussed in the present paper.

image file: c5ra24340h-f3.tif
Fig. 3 Reaction profiles of metal nitrenoid formation from Rh2(esp)2 and 1. The relative Gibbs free energies and thermal energies are presented with Aa, Aa-TS and Ba as the zero points, respectively.

With the coordination between the Rh-atom and α-N-atom in Aa, the atomic charge on α-N-atom decreases which could assist the N2 loss.41 The N–N bond cleavage via the transition state Aa-TS requires a barrier of 19.2 kcal mol−1. The elimination of nitrogen gas is an exothermic process that produces the singlet metal nitrene SBa. The structures located in the reaction pathway from Aa are shown in Fig. 4. The coordination of Rh1–N1 (2.31 Å) in the reactant species Aa is relatively weak while it obviously becomes stronger in the transition state Aa-TS (Rh1–N1, 2.07 Å) with the elongation of N1–N2 bond distance (from 1.26 Å in Aa to 1.63 Å in Aa-TS). From the NBO charge analysis, the rhodium centers would help to stabilize the negative-charged nitrogen atom N1 through the reaction process (see Fig. 4).

image file: c5ra24340h-f4.tif
Fig. 4 Shown are selected optimized structures in the reaction of Rh2(esp)2 (I) and 1. The tethered dicarboxylate ligands (esp) are simplified. Selected NBO charges are in parentheses and bond distances are in angstrom.

When comparing the mechanisms of nitrene formation mediated by Rh2(esp)2 (I) and Rh2(OCHO)4 (II) (see ESI), the whole reaction profiles of N2 extrusion shown in Fig. 3 and S1 exhibit identical patterns for the complete reaction pathway. What's more, the geometric parameters in these two reaction systems are comparative in spite of a few differences. For instance, the Rh1–Rh2 bond is slightly longer in the reaction process of Rh2(OCHO)4 and 1 (Fig. S3) than those of Rh2(esp)2 and 1 (Fig. 4), which is probably due to the compacting enhancement from the “esp” ligand in Rh2(esp)2. From the aspect of energy, the activation energy of Aa-TS (19.2 kcal mol−1) is slightly lower than that of A-TS (20.0 kcal mol−1). This could be ascribed to the weak electron-donating esp ligands.

3.2.2. Metal nitrene mediated amination in Ba. Following the metal nitrene formation, the resulted active intermediates would undergo subsequent nitrene insertion/C–H bond amination. In consideration of the similar reaction mechanisms for the metal nitrenes Ba–d (Fig. S5), only the reactions from Ba (see Fig. 5) and the species on these reaction profiles (Fig. 4) will be further discussed.
image file: c5ra24340h-f5.tif
Fig. 5 Reaction profiles of C–H bond amination mediated by Ba. Spin densities of Rh1–Rh2, N1, C1, Ph(C2–C7) are in parentheses.

As discussed above, the singlet metal nitrene SBa is formed in the extrusion of N2 from Aa (Fig. 3). However, the existence of a minimum energy crossing point (MECP1) between the singlet and the triplet profiles allows the formation of the triplet metal nitrene TBa. At the minimum energy crossing point MECP1 located before the reactants, the singlet nitrenoid and triplet one are quite close in energy.56 It should be mentioned that the relative free energies of MECPs are estimated taking the solvation effects into account. Thus, they represent the most possible location areas rather than the accurate crossing points (see Fig. S6 in ESI). The triplet metal nitrene TBa is more stable than the singlet nitrene SBa by 3.7 kcal mol−1. This is different from the previously reported conclusion obtained from similar reaction systems involving Rh2L4 that the ground triplet state of metal nitrene is estimated to be about 2 kcal mol−1 higher than the singlet state and thus they could coexist with each other.17 Comparing the structures of the singlet and triplet metal nitrenes, SBa and TBa, not only the Rh1–Rh2 and Rh1–N1 bond distances are almost the same, but the dihedral angle D(O1, Rh1, N1, C2) is also comparable in TBa (51°) with that in SBa (48°). On the other hand, the spin densities for Rh1, Rh2, N1 atoms and the phenyl ring (C2–C7) in TBa are 0.35, 0.18, 1.02 and 0.43, respectively (Fig. 5 and Table S3). This means the two unpaired electrons mainly reside on the Rh2 and N1-Ph(C2–C7) moiety.

For the dirhodium reaction complex, the strong d–p orbital interactions between the RhII,II2 center and N1 could stabilize the radical species.19 This would increase the reaction barrier for the H-abstraction process and could possibly further improve the reaction selectivity. This type of metal–metal bonded systems has been extensively discussed in literature and they are suggested to exhibit exceptional efficiency in C–H functionalization rather than mono-metal catalysts. The dirhodium d14 electronic configuration were highly effective at metal to ligand π back-bonding and the filled π* orbital of Rh2L4 could donate electron-pair,57 e.g. the π and π(nb) bonding shown in Fig. S7. This indicates distinctive metal–metal synergism which endues a metal–metal complex reactivity different from a mono-nuclear metal complex.58 Furthermore, the unique catalysis is attributed to the three-center/four-electron (3c/4e) bonds in metal–metal bonded intermediates such as carbene and nitrene intermediates Rh–Rh–C(or N) which is suggested to be described as superelectrophilic by virtue of 3c/4e Rh–Rh–C(or N) s and p bonds.59

In the singlet pathway of C–H bond amination, the C–H bond cleavage, N–H and C–N bond formation through the transition state STS1a requires an energy barrier of 13.5 kcal mol−1 relative to TBa. For Rh2(OCHO)4, the barrier is 12.0 kcal mol−1 relative to TB (Fig. S2 in ESI). The vibration of the unique imaginary frequency (−659.3 cm−1) in STS1a shows an evident H-abstraction process accompanied with an initial C–N bond formation. According to the IRC calculation (see Fig. S9 in ESI), the concerted singlet pathway exhibits asynchronous characteristic that the hydride-like H1 is transferred prior to the formation of N1–C1 bond. This feature can be seen from the angle A(N1, H1, C1) = 133°, and the charge change of H-donor C1(sp3) from −0.69 for SBa to −0.46 for STS1a. However, the weak electron-donating catalyst Rh2(esp)2 cannot stabilize a potential intermediate formed in H-abstraction step featuring a carbocation and a negative nitrogen center. Therefore, no intermediates or transition states are observed on the way from STS1a to the final product SCa. Our previous study has proposed the nature of the singlet pathway is a stepwise process and the fast combination of a carbocation and an electron-sufficient nitrogen center is barrier-free or require an identifiable energy barrier.18

In the triplet pathway, two steps are involved: H-abstraction and C–N bond formation. In the H-abstraction step, the activation energy of the transition state TTS1a is 10.8 kcal mol−1. For Rh2(OCHO)4, the barrier is 9.1 kcal mol−1 relative to TB (Fig. S2 in ESI). The spin density for H-donor (C1) increases significantly from 0.02 in TBa to 0.62 in the triplet transition state TTS1a while the spin density for N1 atom decreases from 1.02 to 0.67. The vibration of the unique imaginary frequency (−1136.1 cm−1) in TTS1a and the IRC calculation for TTS1a (see Fig. S10 in ESI) shows this is a complete hydrogen-migration process and no signs of C–N bond formation. This C–H homolytic cleavage mediated by Rh2(esp)2 results in the intermediate TIM1a. The spin densities for Rh1, Rh2, N1, C1 atoms and the phenyl ring (C2–C7) in TIM1a are 0.24, 0.12, 0.42, 0.98 and 0.33, respectively. It means the two unpaired electrons mainly reside on the C1, Rh2 core and N1-Ph(C2–C7) moiety. The intermediate TIM1a on the triplet reaction profile is close to the triplet transition state TTS1a in energy. This could be attributed to the relatively small geometry change from the transition state to the corresponding reactive intermediate. The diradical intermediate TIM1a rebound in a subsequent step via the radical coupling transition state TTS2a requiring a high barrier (from TBa to TTS2a, 23.5 kcal mol−1; from TIM1a to TTS2a, 14.2 kcal mol−1). For Rh2(OCHO)4, the barrier of the radical coupling is 23.4 kcal mol−1 relative to TB and 15.4 kcal mol−1 relative to TIM1 (Fig. S2 in ESI). As we previously reported, this type of diradical recombination step requires an identifiable energy barrier (∼15 kcal mol−1).18 However, this radical recombination may not be observed, because there exists a spin crossing via MECP2 between the triplet and singlet energy profiles. After spin crossover to the singlet pathway, the final product SCa is reached. Therefore, the overall energy barrier of the triplet pathway is determined by the relative energy of MECP2. It should be mentioned that our previous studies on the reactions of dirhodium tetracarboxylate (Rh2(formate)4 and Rh2(OAc)4) catalyzed nitrene insertion into C–H bonds generally suggest the closed-shell singlet transition state is lower in energy than the open-shell triplet transition state in the H-abstraction step.17–19 Also, we have done calculations of MECPs in amination reactions catalyzed by dirhodium tetracarboxylate and basically MECP is located on the way from the triplet reactant complex to the triplet H-abstraction transition state which suggests a spin crossover to the closed-shell singlet energy profile.18,19

In order to understand the triplet pathway in depth, the mulliken spin distribution along the reaction coordinate for the triplet states is presented in Fig. 6. In the H-abstraction step, the spin density on the Rh2 center in the triplet reactant complex TBa is significantly less than 1.0. With the spin on N1, Rh2, Ph moieties partially transferred to C1 via TTS1a, the spin densities on the Rh2 center decreases further in TIM1a. In the subsequent C–N bond formation step, the spin density on the Rh2 center increases to larger than 1.0 in TTS2a and the triplet product complex TCa holds the major spin density on the Rh2 center. As we previously reported, the RhII,II2 dimer in TTS2a would be oxidized to a mixed-valent RhII,III2 dimer and a NR radical.19 This spin–orbital coupling in the Rh2 center and formation of C–N bond is an energy-consuming process.18

image file: c5ra24340h-f6.tif
Fig. 6 Mulliken spin distribution along the reaction coordinate for the triplet states in reaction of Rh2(esp)2 and 1.

From the metal nitrenes S/TBa to the transition states S/TTS1a, the Rh1–N1 bond elongates slightly and the charge of N1 atom becomes more negative (see Fig. 4). It is worth noting that the dihedral angle D(O1, Rh1, N1, C2) is much smaller in STS1a (19°) than that in SBa (51°) but the values in TTS1a (50°) and TBa (48°) are identical. Comparing the singlet and triplet transition states, STS1a and TTS1a, the distance of N1–H1 in TTS1a is longer and C1–H1 shorter. As seen in the geometry of the final product–catalyst complex SCa, the distance of Rh1–N1 elongates to 2.25 Å which is close to that in Aa (2.31 Å); and Rh1 charge reduces to 0.43 which equals that in Aa.

It should be mentioned that the unstable triplet intermediate TIM1a would possibly go through two alternative C–N formation pathways. One is direct recombination of diradical via TTS2a which is discussed above. Another pathway is a N–H swing/diradical recombination process (see Fig. S8 in ESI). Calculations show that these two pathways in the triplet mechanisms are competitive. Therefore, the N–H swing process could possibly lead to racemic products.18

3.3. Key mechanistic features of dirhodium catalyzed C–H bond amination with aryl azides

From results above, Rh2(esp)2 and Rh2(OCHO)4 (see ESI) catalyzed C–H amination majorly share an identical mechanism, including the PES pattern and the structure features of the reactants, transition states and products. The whole PES for the Rh2(esp)2 case is shown in Fig. 7. The tethered ligands esp of Rh2(esp)2 would not obviously affect the amination reaction mechanism. Based on the experimental observations,39 esp ligand can prevent oxidation in the reaction solution and protect the geometry of the dirhodium complex which increases the conversion of the catalytic reaction cycle. On the other hand, reactions with mononuclear catalysts known to catalyze N-atom-transfer reactions, such as [Rh(cod)2]SO3CF3, [Rh(PPh3)3]Cl and [Rh(cod)OMe]2 (cod = 1,5-cyclooctadiene), are unsuccessful in producing indoline product.39 And as we discussed above, the strong d–p orbital interactions between the RhII,II2 center and nitrene N could stabilize the radical species and could possibly further enhance the reaction selectivity. Therefore, the combination of RhII,II2 dimer and ligands as “security guard” is the key to success of the aliphatic C–H amination involved in this paper.
image file: c5ra24340h-f7.tif
Fig. 7 Reaction profiles of Rh2(esp)2 catalyzed amination of C–H bond.

4. Conclusions

In conclusion, dirhodium catalysts Rh2Ln, such as Rh2(esp)2 and Rh2(OCHO)4, mediated aliphatic C–H bond amination of aryl azides show a general mechanism. Firstly, the dirhodium complex coordinates with the substrate leading to the extrusion of nitrogen gas to produce metal nitrene. This is the rate-determining step and significantly exothermic. A minimum energy crossing point is located in this step and leads to the singlet metal nitrene or the triplet metal nitrene. Secondly, the dirhodium metal nitrene forms C–N bond via intramolecular nitrene insertion to C–H bond through two possible reaction pathways. One is the singlet concerted asynchronous pathway which results in direct insertion of metal nitrene into C–H bond. Another one is the triplet stepwise pathway involving hydrogen atom transfer followed by diradical combination. However, calculations show the diradical recombination requires a relatively high barrier more than 20 kcal mol−1. There is a minimum energy crossing point located between the singlet and triplet pathways which leads the reaction towards the singlet pathway. The tethered ligands joined to the rhodium centers of Rh2(esp)2 give aid to stabilize the substrate-catalyst complex and play a role as “security guard” to protect the dirhodium core, but they do not indicate significant influence on the reaction mechanisms of metal nitrene catalyzed amination of aliphatic C–H bond of aryl azides.


The authors gratefully acknowledge the National Natural Science Foundation of China (Grant No. 21173273, 21203256, 21373277, 21473261, 21573292) and the Guangdong Provincial Natural Science Foundation (No. 2015A030313185, 2015A030306027). This work was partially sponsored by the high-performance grid computing platform of Sun Yat-sen University and supported in part by the Guangdong Province Key Laboratory of Computational Science and the Guangdong Province Computational Science Innovative Research Team.


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Electronic supplementary information (ESI) available: The Cartesian coordinates for the calculated stationary structures. See DOI: 10.1039/c5ra24340h

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