Article pubs.acs.org/Organometallics
Insight into Mechanistic Features of Ruthenium(II)−Pybox-Catalyzed C−H Amination Djamaladdin G. Musaev* and Simon B. Blakey Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States S Supporting Information *
ABSTRACT: The mechanisms and controlling factors of intra- and intermolecular C−H bond amination catalyzed by cationic bis-imido complex [(Pybox)Ru(NSO3CH2CH2CH2R)2Cl]+ (1_R, where R = H, Ph) were elaborated at the density functional level. It was shown that the cis_1_Ph isomer is slightly (2.7 (2.9) [3.6] kcal/mol) lower in energy than trans_1_Ph, and trans_1_Ph → cis_1_Ph isomerization proceeds via formation of the mono-imido complex cis-[(Pybox)Ru(Imd)Cl]+ with a 31.0 (17.0) [9.0] kcal/mol energy barrier. The intramolecular α-, β-, and γ-C−H bond amination processes in trans_1_R are kinetically and thermodynamically feasible, while the required energy barrier decreases via α > β > γ for R = H, Ph. These reactions proceed via a C−H bond insertion pathway, except for the γ-C−H bond amination in trans_1_Ph, which proceeds via an H atom transfer mechanism. The H to Ph substitution on the Cγ atom of the imido ligand only slightly reduces the required energy barriers for α- and β-C−H bond amination in trans_1_R. However, it dramatically reduces the γ-C−H bond amination barrier and switches the mechanism of the reaction from C−H bond insertion to H atom transfer. This dramatic effect is a result of the better electron-withdrawing nature of the Ph ring. Thus, by replacing the R ligand, located at the γ (as well as β) C position, one may control the rate (barrier height), mechanism, and product distribution of the C−H bond amination in trans_1_R. The cis_1_Ph isomer is found to be slightly less reactive than the trans_1_Ph isomer. The intermolecular methane C−H bond amination by trans_1_R cannot compete with the intramolecular reactions in trans_1_R. The intermolecular process becomes feasible only for CβH3CαH2Ph. The intermolecular C−H amination of the substrate CβH3CαH2Ph by cis_1_Ph seems as feasible as that for the trans_1_Ph isomer. Involvement of the monoimido intermediate of the bis-imido complex 1_Ph in intra- and intermolecular C−H amination is highly unlikely.
I. INRODUCTION Recent progress in catalyst development and reaction design has advanced the field of C−H amination to the point where these transformations can be confidently applied in the context of complex molecule synthesis.1 This success is based on the development of more robust catalysts, a number of versatile linker systems that promote high levels of regiocontrol in intramolecular C−H amination reactions and substrates.2 Catalyst design for enantioselective intramolecular C−H amination is quite advanced.3 Despite these significant advances, protocols for predictably efficient intermolecular C−H amination remain elusive. Although there are many reports of intermolecular C−H amination utilizing large excesses of alkane substrate,4 such processes are untenable in the arena of complex molecule functionalization. For a small number of simple substrates, efficient intermolecular C−H amination at 1:1 ratios of alkane substrate and amine source have been developed.5 However, practical selective intermolecular C−H amination lags behind conceptually related C−H oxygenationa field in which recent © 2012 American Chemical Society
methodological advances now allow for the selective modification of complex organic molecules.6 In order to guide further reaction development in the area of intermolecular C−H amination, a thorough understanding of the reaction mechanism is important. This requires comprehensive experimental and computational studies. In the case of dirhodium(II) tetracarboxylate catalysts, both experimental evidence and DFT calculations are consistent with a concerted C−H bond insertion mechanism.7 Recent joint experimental and theoretical studies8 of our group on the mechanism of intramolecular selective C−H allylic amination and aziridination by [Ru2(hp)4Cl] catalyst have convincingly revealed that the C− H bond functionalization in sulfamate occurs via H abstraction followed by a radical recombination mechanism. Experimental studies utilizing ruthenium porphyrin complexes have led to a similar mechanism, H atom abstraction/radical recombination, and have demonstrated that Ru(VI) bis-imido species are active amidating species.9 Computational studies of C−H amination Received: February 27, 2012 Published: June 29, 2012 4950
dx.doi.org/10.1021/om300153q | Organometallics 2012, 31, 4950−4961
Organometallics
Article
with ruthenium porphyrin complexes have confirmed the formation of Ru(IV) monoimido complexes and subsequent C−H amination in these systems.10 In spite of these successes, the situation for ruthenium-catalyzed C−H amination remains more complex. Given the exquisite chemoselectivity exhibited by our cationic ruthenium pybox catalyst,3b here we report further computational investigations necessary to help clarify the reaction pathway and facilitate future reaction design. We address the mechanisms and controlling factors of the intra- and intermolecular C−H bond amination catalyzed by the cationic (pybox)Ru(IV) bis-imido complexes [(Pybox)Ru(NSO3CH2CH2CH2R)2Cl]+ (1_R, where R = H, Ph) (see Figure 1). Since the exact structure of (pybox)Ru(bis-imido)Cl+ is not known, here we study the reaction of both cis[(Pybox)Ru(NSO3CH2CH2CH2R)2Cl]+ (cis-1_R) and trans[(Pybox)Ru(NSO3CH2CH2CH2R)2Cl]+ (trans_1_R) isomers, as well as the mono-imido complex [(Pybox)Ru(NSO3CH2CH2CH2R)Cl]+ (see below).
Figure 1. Calculated structures and important geometrical parameters (in Å) of the most favorable trans and cis isomers of the bis-imido complex[(Pybox)Ru(Imd)2Cl]+ (1_R). Values given in the first line are for R = H, while those in the second line are for R = Ph. Values without and with parentheses are for singlet and triplet states, respectively.
II. COMPUTATIONAL DETAILS All calculations were performed using the Gaussian 09 program.11 The geometries of all species under investigation were optimized without symmetry constraints at the B3LYP12 level of theory in conjunction with lanl2dz basis sets and the corresponding Hay−Wadt effective core potentials (ECPs) for Ru centers13 and 6-31G(d,p) split-valence basis sets for other atoms. This method is subsequently referred to as “B3LYP/[lanl2dz+6-31G(d,p)]”. For all species under investigation, Hessian matrices were calculated, and all transition states were confirmed to have one imaginary frequency corresponding to the reaction coordinates. Their nature was confirmed by performing quasiIRC (intrinsic reaction coordinate) calculations. Solvent effects were estimated at the B3LYP/[lanl2dz +6-31G(d,p)] level of theory using the PCM (polarizable continuum model) method14 at the gas-phase optimized geometries. In these calculations CH2Cl2 was used as a solvent. Below, we discuss gas-phase enthalpy ΔH values at 298.15 K and 1 atm, while the calculated gas-phase Gibbs free energies (calculated also at 298.15 K and 1 atm) are presented in parentheses. The solvated free energies, ΔGs, estimated as ΔGs = ΔGsol(PCM-calculated) + [ΔE − ΔG]gas, are provided in brackets. The Cartesian coordinates and energetics of all B3LYP/[lanl2dz+6-31G(d,p)] optimized structures are presented in the Supporting Information (Tables S1−S4).
mechanisms. The first starts by Cl dissociation from trans_1_Ph, leading to formation of trans-[(Pybox)Ru(Imd)2]2+ , followed by trans-[(Pybox)Ru(Imd)2]2+ → cis-[(Pybox)Ru(Imd)2]2+ isomerization, and is completed upon coordination of Cl− to cis-[(Pybox)Ru(Imd)2]2+ at the axial position. Calculations show that the first step of this pathway, i.e. the reaction trans_1_Ph → [(Pybox)Ru(Imd)2]2+ + Cl−, is highly (ΔGS = [44.0] kcal/mol) endothermic and cannot occur under milder experimental conditions. The second pathway starts with the Imd ligand dissociation from trans_1_Ph, leading to formation of cis-[(Pybox)Ru(Imd)Cl]+, followed by cis-[(Pybox)Ru(Imd)Cl]+ → trans-[(Pybox)Ru(Imd)Cl]+ isomerization, and is completed by coordination of the Imd ligand at an equatorial position to form cis-[(Pybox)Ru(Imd)2Cl]+. Calculations show that Imd dissociation from trans_1_Ph, i.e. the reaction trans_1_Ph (singlet) → cis-[(Pybox)Ru(Imd)Cl]+ (singlet) + Imd (triplet), requires 31.0 (17.0) [9.0] kcal/mol of energy. Furthermore, the isomer trans-[(Pybox)Ru(Imd)Cl]+ does not exist and barrierlessly converges to cis-[(Pybox)Ru(Imd)Cl]+. These findings indicate that the process starting with Imd dissociation is more favorable than that initiated by Cl− dissociation. Thus, both trans_1_R and cis_1_R could be the prereaction complex for intra- and intermolecular C−H bond amination. As seen in Table 2, the ground electronic states of the bis(imido) trans_1_R (R = H, Ph) complexes are closed-shell singlet (CSS) states (with ⟨S2⟩ = 0.00). In the singlet states, Ru−N1/Ru−N2 bond distances are 1.819/1.819 and 1.819/1.819 Å for trans_1_H and trans_1_Ph, respectively, which indicates multiple-bond character of the Ru− N1 and Ru−N2 bonds. Indeed, interaction of the ground singlet electronic state of (Pybox)Ru−Cl (with a [(dxz)2(dyz)2(dxy)2(dxx‑yy)0(dzz)0] electronic configuration) with the triplet ground state of NSO2OR groups (containing the (spz)2(px)1(py)1 valence orbitals of N1 and N1 centers) can provide one σ and two π four-electron−three-center N1−Ru−N2 bonds (see Scheme 1). However, the performed natural bond analysis shows that electrons in the σ bond are localized mainly on the N centers; i.e., the σ component of Ru−N1 and Ru−N2 bonds is expected to be weak (see Figure S2 of the Supporting Information).
III. RESULTS AND DISCUSSION A. Prereaction Complexes. In general, the 1_R complex [(Pybox)Ru(Imd)2Cl]+ (where Imd = NSO3CH2CH2CH2R with R = H, Ph), may have cis and trans isomers, cis_1_R and trans_1_R, with imido groups at positions cis and trans to each other, respectively (Figure 1). In their turns, both cis_1_R and trans_1_R may have several isomers, some of which are presented in Figure S1 of the Supporting Information. Full geometry parameters of all studied isomers are given in the Supporting Information (Table S4), while the calculated structure of the energetically most favorable cis_1_R and trans_1_R isomers with the atomic notations used and important geometry parameters are given in Figure 1. The calculated spin density on important atoms (and ⟨S2⟩ values) and relative energies of the calculated structures are presented in Tables 1−4. Our extensive studies show that cis_1_Ph has degenerate open-shell singlet and triplet state pairs (see Table 1). In its openshell singlet state, cis_1_Ph is slightly (2.7 (2.9) [3.6] kcal/mol) lower in energy than the closed-shell singlet ground state of trans_1_Ph. In general, the trans_1_Ph → cis_1_Ph isomerization may proceed via two different dissociative−associative 4951
dx.doi.org/10.1021/om300153q | Organometallics 2012, 31, 4950−4961
Organometallics
Article
Table 1. Calculated Spin Densities (in e) of important Atoms of Reactants, Intermediates, Transition States and Products of the Intramolecular γ-C−H and Intermolecular Cα−H Bond of CH3CH2Ph in cis_1_Ph cis_1_Ph_TSγ
cis_1_Ph atom Ru N1 N2 Cγ Ph Cl ⟨S2⟩
1
A
−0.04 −0.96 1.01 0.00 0.00 −0.04 1.28
3
A
0.62 0.90 0.24 0.00 0.00 0.03 2.09
1
A
0.30 0.93 −0.82 −0.36 −0.24 0.08 1.54
3
cis_1_Ph_P1γ A
0.91 0.83 0.17 −0.09 −0.07 0.07 2.22
1
A
0.00
Furthermore, four-electron−three-center N1−Ru−N2 πbonding orbitals have only 1.61e electron population each and their antibonding counterparts are populated by ∼0.40e, which makes these π-bonds similarly weak. These conclusions from the NBO analysis are consistent with the calculated Wiberg index of 1.38, which indicates more than single but less than double bond character of RuN1 and RuN2. The triplet states of trans_1_H and trans_1_Ph are 5.9 (3.3) and 5.3 (4.2) kcal/mol higher than their CSS states, respectively (see Table 3). In the triplet states, almost all unpaired electrons are located on the N centers of Imd ligands. This spin density distribution is consistent with the nature of the singlet−triplet transition associated with the promotion of one electron from the N1−Ru− N2 bonding (four-electron−three-center bond) orbital (see Figure 2) to the N1−Ru−N2 nonbonding MO. The calculated Ru−N1/Ru−N2 bond distances for the singlet and triplet states are also consistent with the nature of this transition. However, in the triplet states, these bond distances are elongated to 1.940/ 1.940 and 1.933/1.943 Å, respectively. As mentioned above, triplet and open-shell singlet states of cis_1_R (R = Ph) are energetically degenerate with Ru−N1 and Ru−N2 bond distances of 1.901 (1.920) and 1.847 (1.811) Å. The former bond distance is slightly longer than the latter because of the trans influence of the Cl ligand. The calculated Ru−N1 bond distance is 1.787 (1.834) Å for the closed-shell singlet ground state and excited triplet state of monoimido intermediate cis_1a_Ph. One should mention that isolation and characterization of elusive RuNSO2OR complexes remains a serious challenge. Therefore, we may only compare the calculated RuNSO2OR bond distances of 1.940/1.940 and 1.933/1.943 Å for trans_1_H and trans_1_Ph, respectively, with only 2.00(1) Å reported for [RuVI(TMP)(NHC)(pz)].9c Also, the calculated Ru−N bond distance 1.787 (1.834) Å for the mono-imido complex cis[(Pybox)Ru(Imd)Cl]+ is in excellent agreement with 1.74 (1.82) Å reported for the (PNP)Ru(NPh)+ complex.15 Throughout the paper we denote the located transition states and products of the intramolecular C−H amination as Z_TSx and Z_Pnx, respectively, where Z stands for reactant complexes trans_1_R (R = H,/ Ph) and cis_1_Ph, x = α, β, and γ, and n = 1, 2, etc. For the intermolecular C−H bond amination reactions with CH4 and CH3CH2Ph substrates we use notations such as Z_TSex,S and Z_Pnex,S, where S = CH4, CH3CH2Ph.
