Iodide-enhanced palladium catalysis via formation of iodide-bridged binuclear palladium complex

The prevalence of metalloenzymes with multinuclear metal complexes in their active sites inspires chemists’ interest in the development of multinuclear catalysts. Studies in this area commonly focus on binuclear catalysts containing either metal-metal bond or electronically discrete, conformationally advantageous metal centres connected by multidentate ligands, while in many multinuclear metalloenzymes the metal centres are bridged through μ2-ligands without a metal-metal bond. We report herein a μ2-iodide-bridged binuclear palladium catalyst which accelerates the C-H nitrosation/annulation reaction and significantly enhances its yield compared with palladium acetate catalyst. The superior activity of this binuclear palladium catalyst is attributed to the trans effect-relay through the iodide bridge from one palladium sphere to the other palladium sphere, which facilitates dissociation of the stable six-membered chelating ring in palladium intermediate and accelerates the catalytic cycle. Such a trans effect-relay represents a bimetallic cooperation mode and may open an avenue to design and develop multinuclear catalysts.

90 C for 12 h. The reaction mixture was cooled to room temperature, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (eluent: 5-10% CH 2 Cl 2 /hexane) to provide the corresponding product 4b (Binuclear Pd II -I complex, red solid, 68.2 mg, 65%) and [Pd 2 I 6 ]( n Bu 4 N) 2

Stoichiometric reaction of 4b with [NO][BF 4 ] to form 3b
In a glove box, a 25 mL of the Schlenk tube equipped with a stir bar was charged with 4b (0.1 mmol, 0.1053 g), [NO] [BF 4 ] (0.6 mmol, 0.0701 g) and DCB (5 mL). The tube was sealed and removed out of the glove box. The reaction mixture was stirred at room temperature for 24 h. Upon completion, the reaction mixture was purified directly by chromatography on silica gel (eluent: 5-10% ether/hexane) to provide the corresponding product 3b (yellow oil, 24.6 mg, 38%).

Conversion of the acetate-bridged binuclear palladium complex to the corresponding iodide-bridged binuclear palladium complex and the regeneration of iodide-bridged binuclear palladium complex under the conditions mimicking catalytic reaction: Preparation of the acetate-bridged binuclear palladium complex with cyclopalladated (E)-bis(4-butylphenyl)diazene
Procedure: In a glove box, a 25 mL of the Schlenk tube equipped with a stir bar was charged with Pd(OAc) 2 (0.2 mmol, 0.0449), anhydrous p-toluenesulfonic acid (0.4 mmol, 0.0689 g), 1b (0.6 mmol, 0.1766 g) and DCB (3 mL). The tube was sealed and removed out of the glove box. The reaction mixture was stirred at 90 C for 12 h. Upon completion, the reaction mixture was purified directly by chromatography on silica gel (eluent: 1-5% MeOH/CH 2 Cl 2 ) to provide the corresponding product 5b (Binuclear Pd II -OAc complex, black red solid, trans : cis = 5.71 : 1, 71.7 mg, 78%). 1 6.18; N, 6.14. The structure of 5b was established by single-crystal X-ray diffraction analysis (see below). Procedure: In a glove box, a 25 mL of the Schlenk tube equipped with a stir bar was charged with 5b (0.1 mmol, 0.0917 g), TBAI (0.4 mmol, 0.0738 g) and DCB (3 mL). The tube was sealed and removed out of the glove box. The reaction mixture was stirred at 90 C for 12 h. Upon completion, the reaction mixture was purified directly by chromatography on silica gel (eluent: 5-10% CH 2 Cl 2 /hexane) to provide the corresponding product 4b (77.9 mg, 74%).

Experiment for the regeneration of 4b under the conditions mimicking catalytic reaction:
Procedure: In a glove box, a 50 mL of the Schlenk tube equipped with a stir bar was charged with 4b (0.1 mol, 0.1053 g), 1b (1.0 mmol, 0.2944 g), [NO][BF 4 ] (0.3 mmol, 0.0351 g) and DCB (10 mL). The tube was sealed and removed out of the glove box. The reaction mixture was stirred at 90 C for 4 h. Upon completion, the reaction mixture was cooled down to room temperature, then NEt 3 (1.5 mmol, 0.1521 g) in 1 mL MeOH was injected by a syringe under N 2 atmosphere to neutralize the acid formed in the reaction and extra [NO] [BF 4 ]. The mixture was diluted with 10 mL of ethyl acetate, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the ethyl acetate (10 mL). The filtrate was concentrated under reduced pressure. The residue was then purified by chromatography on silica gel to provide product 3b (43.5 mg, 133%), at the same time, 4b (22.1 mg, 21%) was also recovered. Procedure: In a glove box, a 25 mL of the Schlenk tube equipped with a stir bar was charged with [Pd 2 I 6 ]( n Bu 4 N) 2 (1.5 mol%, 0.0043 g), 1a (0.2 mmol, 0.0364 g), [NO][BF 4 ] (0.4 mmol, 0.0468g) and DCB (1.5 mL). The tube was sealed and removed out of the glove box. The reaction mixture was stirred at 80 C for 24 h. Upon completion, the reaction mixture was diluted with 10 mL of ethyl acetate, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the ethyl acetate (20 mL). The filtrate was concentrated under reduced pressure. The residue was then purified by chromatography on silica gel to provide product 3a (34.9 mg, 82%). mmol, 0.3221 g) and DCB (15 mL). The flask was sealed and removed out of the glove box. The reaction mixture was stirred at room temperature for 5 min and then 90 C. The samples were obtained at the indicated time using syringes with long needles which were filled with N 2 before use. Filtered the samples with a pad of silica gel and washed with 1.5 mL MeOH. The concentrations of 3c were determined by HPLC analysis. The reaction was monitored to approximately 10-15% conversion.
The Initial rate with Pd(OAc) 2

Supplementary
[NO][BF 4 ] (6 mmol, 0.7008 g), internal stardard 3,4-dichlorotoluene (2 mmol, 0.3221 g) and DCB (5 mL) were added. The flask was sealed and removed out of the glove box. The reaction mixture was stirred at room temperature for 5 min and then 90 C.  Following the above mentioned procedure: the reaction was carried out with 5b (1.5 mol%, 0.0275 g), anhydrous p-toluenesulfonic acid (6 mol%, 0.0206 g), HOAc (3 mol%, 0.0036 g), 1c (2 mmol, 0.4204 g), [NO][BF 4 ] (6 mmol, 0.7008 g) and internal stardard 3,4-dichlorotoluene (2 mmol, 0.3221 g) in DCB (15 mL).  The initial rates were 0.00117, 0.00188, 0.00231, and 0.00115 with regard to condition A, B, C, and D respectively. The initial rate of binuclear Pd-I species 4b is two times as fast as Pd(OAc) 2 and TsOH catalytic system and is more fast than Pd(OAc) 2 , TBAI and TsOH catalytic system, therefore indicating that 4b is a kinetically competent catalyst for the reaction. The initial rate of binuclear Pd-OAc species 5b is almost the same as Pd(OAc) 2 and TsOH catalytic system, thus 5b is the kinetically competent catalyst when without the addition of TBAI.

Determination of the order in 4b
The order in 4b was obtained by determining the initial rate of reactions with different [4b].
Following the above mentioned procedure: the reaction was carried out with 4b (1.5 mol%, 0.0316 g), 1c (2 mmol, 0.4204 g), [NO][BF 4 ] (6 mmol, 0.7008 g) and internal stardard 3,4-dichlorotoluene (2 mmol, 0.3221 g) in DCB (15 mL). The flask was sealed and removed out of the glove box. The reaction mixture was stirred at room temperature for 5 min and then 90 C.    The tube was sealed and removed out of the glove box. The reaction mixture was stirred at 80 C for indicated time. Upon completion, the reaction mixture was diluted with 10 mL of CH 3 CN, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the CH 3 CN (20 mL). The filtrate was diluted with CH 3 CN to 100 mL. The concentrations of 3b were determined by HPLC analysis.

Preparation of azobene starting materials Synthesis of symmetric azobenzenes 1
A 100 mL round flask was equipped with a stir bar was charged with CuBr (6 mol%), pyridine (18 mol%), aniline (5 mmol) in toluene (20 mL). The reaction mixture was vigorously stirred at 60 °C for 20 h under air or O 2 (1 atm). After cooling down to room temperature and concentrating in vacuum, the residue was purified by flash chromatography on silica gel.

Synthesis of unsymmetric azobenzenes 2-4
Substituted aniline (10 mmol) was dissolved in 30 mL of DCM. To this solution Oxone (15 mmol) dissolved in 30 ml of water was added. The solution was stirred under nitrogen at room temperature until TLC monitoring indicated complete consumption of the starting material. After separation of the layers, the aqueous layer was extracted with DCM twice. The combined organic layers were washed with 1N HCl twice, saturated sodium bicarbonate solution, water, brine and dried (sodium sulfate), filtered. The filtrate was concentrated under reduced pressure and the crude products were used without further purifications. To a round bottom flask equipped with a magnetic stir bar was combined the indicated aniline (6-10 mmol, 1.2-2 equiv) and the indicated nitrosobenzene (5 mmol) in glacial acetic acid (30 mL). The reaction solution was stirred at room temperature for 48 h. Upon completion, the reaction mixture was concentrated under reduced pressure. The residue was then purified by chromatography on silica gel. 1a-1l, 1n-1q, 1t, 1ab, 1ad-1ae are known compounds, and the analytical data are consistent with previously reported data. [1][2][5][6][7][8][9][10][11] Analytical data for new azobenzenes

Computational Section
Computational methods. All geometry optimizations were carried out with the hybrid density functional theory (DFT) at the level of M06 12 using DZP basis sets. Here, the DZP stands for a basis set that employs 6-31G(d) all-electron basis set 13 for H, C, N, and O atoms, and the corresponding basis sets with the Stuttgart/Dresden effective-core potential (SDD) [14][15][16] for the palladium and iodine atoms. Analytical frequencies were calculated to confirm the correctness of the structure of either a local minimum or a transition state (TS). The solvation effects were considered using the IEF-PCM model 17 with 1,2-dichlorobenzene as the model solvent. A step size of 0.1 amu 1/2 bohr was used in the IRC (intrinsic reaction coordinate) procedure 18 to check the connectivity between a transition state and the reactant as well as the product.
The optimized structures are then adopted to calculate the free energies at the level of M06 functional 12 with TZP basis sets. Here TZP stands for a basis set that employs a 6-311++G(2d,2p) all-electron basis set 19 for the main group elements (6-311G(d) for iodine atom) 20 and the corresponding basis sets with the Stuttgart/Dresden effective-core potential (SDD) 14 The first term in the right-hand side is the electronic energy computed at M06/TZP level in gas phase. The second term is the thermal correction to the free energy of the solute in the solution phase at M06/DZP level. The third term is the solvation free energy. The last term denotes the free energy correction from the gas-phase standard state (1 atm) to the solution phase standard state of 1 M. It should be noted that the solvation free energy ∆G solv was obtained by using SMD model 24 at the level of B3LYP/6-31G(d) to make it consistent with the specific methods used in the development of such solvation model. [21][22][23] All calculations were carried out using the Gaussian 09 program. 25 As shown, all of the considered coordination steps are endothermic. It is worthy to note the distances between Pd center and azobenezene 1a are too long for an effective chemical interaction. We suggest the steric repulsion between the axial azobenezene 1a and equatorial ligands hinders the coordination. Figure 16. Optimized structures for (a) acetate-bridged bipalladium species 5a and LM1, and (b) iodide-bridged bipalladium species 4a and LM1'. LM1 could be considered as a Pd(III)-Pd(III) species with a direct chemical interaction between the two palladium atoms. However, LM1' should be a Pd(II)-Pd(IV) species without the direct Pd-Pd interaction.

X-ray Crystallographic Analysis
Supplementary Theta range for data collection 3.97 to 70.00°.