Computational Studies on an Aminomethylation Precursor: (Xantphos

Article pubs.acs.org/Organometallics

Computational Studies on an Aminomethylation Precursor: (Xantphos)Pd(CH2NBn2)+ Xiaotian Qi,† Song Liu,† and Yu Lan* School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, People’s Republic of China S Supporting Information *

ABSTRACT: (Xantphos)Pd(CH2NBn2)+ is an important precursor for aminomethylation reactions. In this study, density functional theory is used to clarify the structure of the complex and the mechanism of these types of reactions. The complex can be described as a mixture of square-planar nitrogen-coordinated aminomethyl−Pd(II) and triangular iminium-coordinated Pd(0). Frontier molecular orbital analysis favors the latter. The mechanisms of selected aminomethylation reactions are investigated by density functional theory calculations. The computational results reveal that the Xantphos ligand aids in forming iminium-coordinated palladium complexes, promotes the reductive elimination step of aminomethylation, and can stabilize Pd(0) species.

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INTRODUCTION

Scheme 1. Synthesis of Huang Aminomethylation Precursor and Applications of the Complex

Metallocatalysis is the core of modern chemistry and has received much attention in the past half a century. Organometallic species, especially the well-defined organometallic leading compounds, have made huge contributions to this field.1 For instance, the discovery and structural determination of (π-allyl)palladium species in the past three decades set up the foundation of the current allylpalldium chemistry and boosted the development of this area with huge research interest.2 Other well-studied organometallic leading compounds, such as carbene−Pd3 and carbene−Ru complexes,4 all facilitated the mechanistic understanding of these fields and contributed a great deal to the success of these fields. Therefore, a clearly defined organometallic leading compound during the catalysis could avoid the ambiguity and help researchers design and develop more efficient reaction systems.5 Allylic amines are important moieties that are often contained in pharmaceuticals, natural products, and synthetic intermediates.6 Much effort has been devoted to develop effective methods to access these structures.7 Among these, transition-metal-catalyzed aminomethylation of alkenes is one of the most effective ways to achieve this goal.8 Recently, Huang et al. reported the new precursor (Xantphos)Pd(CH2NBn2)+, which can be synthesized by the reaction between Pd(Xantphos)(CH3CN)2(OTf)2 and aminal followed by a confirmation with X-ray analysis.8c As shown in Scheme 1, when this complex is successfully prepared, it can be used as a leading complex for the synthesis of allylamines,8c amino acetals,9 1,3-diamines,10 and amino acids11 with good step and atom economy. Here, density functional theory (DFT) is used to study the structure and reactivity of Huang complex 1. © XXXX American Chemical Society

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COMPUTATIONAL METHODS

All of the DFT calculations were carried out with the Gaussian 09 series of programs.12 The B3-LYP13 functional with the standard 631G(d) basis set (SDD for Pd atoms) was used for geometry optimizations. The orbital information is given at the same theoretical level. Harmonic vibrational frequency calculations were performed for all stationary points to determine whether they are local minima or transition structures and to derive thermochemical corrections for the enthalpies and free energies. The M11-L functional14 proposed by Truhlar et al. with the 6-311+g(d) basis set (SDD for Pd atoms) was Special Issue: Organometallics in Asia Received: March 22, 2016

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DOI: 10.1021/acs.organomet.6b00234 Organometallics XXXX, XXX, XXX−XXX

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Organometallics used to calculate the single-point energies, because it is expected that this strategy will provide greater accuracy with regard to the energetic information.15 The solvent effects were considered by single-point calculations of the gas-phase stationary points with the SMD continuum model.16 The energies reported in this paper are the M11-L calculated Gibbs free energies in isopropyl alcohol solvent on the basis of B3-LYP calculated geometries with thermodynamic corrections calculated at the same level.

moiety acts as a monodentate ligand coordinated with Pd(0) in resonance structure 1-RS2, and the formal positive charge is mainly localized on the aminium moiety. The real structure of complex 1 would be a mixture of resonance structures 1-RS1 and 1-RS2. On the other hand, the bond orders of Pd−C, Pd− N, and C−N are determined to be 0.322, 0.135, and 0.965, respectively, which indicate that the Pd−C and Pd−N bonds are very weak. More importantly, these data support that the C−N is a double bond and 1-RS2 is most likely to be the main structure of Huang complex 1. The frontier molecular orbitals (FMOs) of Huang complex 1 were calculated at the B3-LYP level with the 6-31g(d) basis set (SDD basis set for Pd). As shown in Figure 2, the lowest

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RESULTS AND DISCUSSION The B3-LYP optimized structure of Huang complex 1 is shown in Figure 1a, which is close to the experimental structure

Figure 2. FMOs of Huang complex 1.

unoccupied molecular orbital (LUMO) of complex 1 is the antibonding orbital of the dπ−pπ back-donation bond, which indicates a dπ−pπ back-donation interaction. The corresponding bonding orbital is also observed as HOMO-20. Thus, the LUMO and HOMO-20 of complex 1 are almost exclusively represented by the π-coordination of iminium, indicating the major contribution is from resonance structure 1-RS2. As shown in Figure 3a, palladium-catalyzed aminomethylation with tetrabenzylmethanediamine 2 of styrene is used as a model reaction to theoretically investigate formation of the Huang complex and its reactivity. In this study, alkylpalladium complex 4 is set to zero energy because the generation of intermediate 4 is irreversible. β-Hydride elimination takes place via transition state 5-ts with an energy barrier of 20.6 kcal/mol to give olefin-coordinated protonated palladium complex 6. Deprotonation by methanediamine to form Xantphos-coordinated Pd(0) complex 7 is exothermic by 7.6 kcal/mol with the release of product 3. SN2-type nucleophilic substitution occurs between nucleophile 7 and protonated aminomethaneaminium 8 via transition state 9-ts with an energy barrier of 8.1 kcal/mol. After release of one molecule of dibenzylamine, formation of Huang complex 1 is exothermic by 0.7 kcal/mol in comparison with intermediate 4. Coordination of styrene then breaks the Pd−N bond to give intermediate 10 (endothermic by 13.2 kcal/mol). Olefin insertion then takes place via transition state 11-ts with an energy barrier of 35.3 kcal/mol to regenerate intermediate 4, which is the rate-limiting step for the complete catalytic cycle. As a comparison, 1,2-bis(diphenylphosphino)ethane (DPPE) was also used as the ligand in the same reaction. As shown in Figure 3b, the energy barrier of the β-hydride elimination step with the DPPE ligand via transition state 5a-ts is similar to that with the Xantphos ligand. However, the deprotonation step with the DPPE ligand is endothermic by 8.7 kcal/mol, which is different from the same step with the Xantphos ligand

Figure 1. (a) B3-LYP optimized structure of Huang complex 1. The bond lengths are given in angstroms. The values in blue are the corresponding geometry information observed from the X-ray structure. (b) Electrostatic potential map, NBO charge, and bond order calculated for Huang complex 1. (c) Resonance structures of Huang complex 1.

obtained by X-ray diffraction.8c The geometry information shows that the carbon and nitrogen atoms in the aminomethyl moiety, the palladium atom, and the two coordinated phosphorus atoms are in the same plane. The calculated Pd− C and Pd−N bond lengths are 2.05 and 2.24 Å, respectively, which represent two normal single bonds. However, the calculated N−Pd−C bond angle is only 37.8°, which indicates that the aminomethyl moiety could also be considered as a monodentate ligand η2 coordinated with palladium. The calculated C−N bond length is 1.40 Å, which is between a typical C−N single bond and CN double bond. Moreover, the P−Pd−P bond angle is 110.5° because of the strain of the Xantphos ligand, which also indicates that the coordination mode of palladium is between tri- and tetracoordination. In addition, the charge distribution on Huang complex 1 has also been studied. The electrostatic potential map is shown in Figure 1b; the NBO charge located on the P−Pd−P moiety is determined to be 0.666 and the NBO charge located on the iminium moiety is 0.334. This result is consistent with the resonance structures of Huang complex 1 (Figure 1c). In resonance structure 1-RS1, the Pd−C bond is a normal single bond, and Pd−N is a coordination bond. The formal positive charge is localized on palladium, and the formal oxidation state of palladium is +2. Alternatively, the aminium B

DOI: 10.1021/acs.organomet.6b00234 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

Figure 3. Free energy profiles for palladium-catalyzed aminomethylation of styrene using (a) the Xantphos ligand and (b) the DPPE ligand. Energy values are given in kcal/mol and represent the relative free energies calculated using the M11-L method in isopropyl alcohol. The values in parentheses are the relative free energies calculated using the B3-LYP method in the gas phase.

(exothermic by 7.6 kcal/mol). The relative free energy of 7a is 25.1 kcal/mol, which is 14.3 kcal/mol higher than that of intermediate 7. Because of the higher relative free energy of intermediate 7a, the overall activation free energy of the nucleophilic substitution via transition state 9a-ts is 32.5 kcal/ mol, which is also much higher than the same step with the Xantphos ligand. Formation of complex 1a is endothermic by 7.6 kcal/mol, whereas that of the corresponding Huang complex 1 is exothermic by 0.7 kcal/mol. The theoretical results clearly show that Pd(0) species can be stabilized by the Xantphos ligand, and nucleophilic substitution for the formation of the Huang complex is assisted by the Xantphos ligand because of stabilization of the Pd(0) species. To further investigate the ligand effect of Xantphos, the free energy profiles for the synthesis of aminals catalyzed by Xantphos-coordinated palladium was theoretically investigated (see Figure S1 in the Supporting Information). The calculated results show that the rate-determining step for the synthesis of amino acid esters is the reductive elimination step. As shown in Scheme 2, when Xantphos is used as the ligand, intermediate 14 is formed by substrate loading. Reductive elimination takes place via transition state 15-ts with an energy barrier of 34.3 kcal/mol, and a Pd(0) species is formed (exothermic by 32.2 kcal/mol). As a comparison, DPPE was also considered for the C−N bond formation. However, when DPPE is used, the barrier of reductive elimination is 51.7 kcal/mol, and the reaction free energy is exothermic by 15.0 kcal/mol. The DFT calculations clearly reveal that reductive elimination is promoted by the Xantphos ligand, and Pd(0) species can be stabilized by the Xantphos ligand.

Scheme 2. Reductive Elimination Step for the Synthesis of Amino Acid Esters Catalyzed by Xantphos-Coordinated Palladium

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CONCLUSION In summary, (Xantphos)Pd(CH 2 NBn2 ) + is a powerful precursor for aminomethylation reactions. The complex can be described as a mixture of square-planar nitrogen-coordinated aminomethyl−Pd(II) and triangular iminium-coordinated Pd(0). FMO analysis favors the latter. DFT studies of the mechanism of some aminomethylation reactions indicate that Xantphos aids in the formation of iminium-coordinated palladium complexes. Pd(0) species can be stabilized by the Xantphos ligand, and the ligand also promotes the reductive C

DOI: 10.1021/acs.organomet.6b00234 Organometallics XXXX, XXX, XXX−XXX

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Organometallics

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elimination step in palladium-catalyzed aminomethylation reactions.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.6b00234. Energies of all reported structures and full authorship of Gaussian 09 (PDF) Cartesian coordinates (XYZ)

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AUTHOR INFORMATION

Corresponding Author

*E-mail for Y.L.: [email protected]. Author Contributions †

These authors contributed equally to this work.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Chinese Academy of Sciences, the NSFC (Nos. 21372266 and 51302327). We are also thankful for the Foundation of 100Young Chongqing University (Project 0903005203191) and the project (No. 106112015CDJZR228806) supported by the Fundamental Research Funds for the Central Universities (Chongqing University).

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DOI: 10.1021/acs.organomet.6b00234 Organometallics XXXX, XXX, XXX−XXX