Origins of unique gold-catalysed chemo- and site-selective C–H functionalization of phenols with diazo compounds† †Electronic supplementary information (ESI) available: Data for new compounds, experimental procedures and theoretical studies on mechanisms. See DOI: 10.1039/c5sc04319k

The origins of unique gold-catalyzed C–H functionalization of phenols with diazo compounds were disclosed by combined computational and experimental studies.

[c] Then conversion of 1 is 100% and the major product is dimer of 1.
[d] Trace of dimer was detected.
[e] The reaction time means the time after finishing the injection of 1.

General procedure for this process:
In a dried glass tube, to a mixture of metal catalyst (5 mol%) and Phenol (56.4 mg, 0.6 mmol) in CH 2 Cl 2 (4 mL) was added diazo compound (70 mg, 0.4 mmol) in 1 mL of CH 2 Cl 2 by a syringe in a period of 15 min at room temperature. The resulting mixture was continually stirred at room temperature until 1 was consumed completely determined by TLC analysis. The mixture was passed through a short silica gel column and then concentrated under reduced pressure. The yield was determined by 1 H-NMR of crude product, using CH 2 Br 2 as internal standard S3 Section 2: Control experiments I.
Subsequently, diazo compound 1 (70 mg, 0.4 mmol) in 1 mL of CH 2 Cl 2 was added by a syringe in a period of 15 min at room temperature. The resulting mixture was continually stirred at room temperature until 1 was consumed completely determined by TLC analysis. The mixture was passed through a short silica gel column and then concentrated under reduced pressure. The deuterium ratio was determined by 1 H-NMR of crude product, using CH 2 Br 2 as internal standard.

Procedure for eq. 2:
In a dried glass tube, to a mixture of gold catalyst (PhO) 3 PAuCl (10.8 mg, 0.02 mmol) in CH 2 Cl 2 (4 mL) was added AgSbF 6 (6.9 mg, 0.02 mmol) and stirred for 15 min at room temperature. Then, compound 3 (96.8 mg, 0.6 mmol) and D 2 O (7.2 μL, 0.4 mmol) were added. The reaction was continually stirred for 15 min at room temperature. The mixture was passed through a short silica gel column and then concentrated under reduced pressure. The deuterium ratio was determined by 1 H-NMR of crude product, using CH 2 Br 2 as internal standard.

S4
In a dried glass tube, to a mixture of gold catalyst (PhO) 3 PAuCl (10.8 mg, 0.02 mmol) in CH 2 Cl 2 (4 mL) was added AgSbF 6 (6.9 mg, 0.02 mmol) and stirred for 15 min at room temperature. Then, phenol 2-5d (59.4 mg, 0.6 mmol) was added and diazo compound 1 (70 mg, 0.4 mmol) in 1 mL of CH 2 Cl 2 was added by a syringe in a period of 15 min at room temperature. The resulting mixture was continually stirred at room temperature until 1 was consumed completely determined by TLC analysis. The mixture was passed through a short silica gel column and then concentrated under reduced pressure. The deuterium ratio was determined by 1 H-NMR of crude product, using CH 2 Br 2 as internal standard.
Combined above results and DFT calculations, the pathway involving Büchner reaction might be ruled out.
Reaction at various temperatures.

Order for phenol
To a dried glass tube was added Phenol solution (0.1 mmol, 0.2 mmol, 0.3 mmol, 0.4 mmol, 0.5 mmol, respectively, 1 M in CH 2 Cl 2 ) and (2, 4-t BuC 6 H 3 O) 3 PAuSbF 6 (0.01 mmol, 0.01 M in CH 2 Cl 2 ), which was preformed prior to be used. Subsequently, CH 2 Cl 2 was added, keeping the reaction volume is equal to 3.8 mL. The reaction was cooled to -45 o C and diazo (0.2 mmol, 0.2 mL solution in CH 2 Cl 2 ) was added and stirred at -45 o C for 1h. The reaction was quenched with diluted Et 3 N solution in acetone. The yield was determined by GC-MS with dodecane (7.8 mg, 10 μL) as internal standard.

Order for gold catalyst.
The procedure was followed as phenol Plot of Δ[pro-c8]/Δt *10 4 vs initial concentration of gold catalyst.   Although there was huge difference between the reactions run at different temperatures, the results of kinetic studies at -45 o C provided certain reference significance to the mechanistic insight at room temperature. As shown in figure 1, the rate-determining step was transformation from Int- c4 to Int-c7. As a result, the reaction rate is depended on the concentration of Int-c4 and water.

Explanation for reaction order of each components.
Besides, the concentration of Int-c4 was determined by the process of formation of Int-c2. It is known that the generation rate of Int-c2 was determined by concentration of phenol and gold carbene. However, compared to concentration of gold carbene, the concentration of phenol was regarded as constant. Based on this point, the formation rate of Int-c2 is just determined by concentration of gold carbene, while the formation rate of gold carbene is relied on the concentration of diazo compound and gold catalyst. As a result, the reaction rate is depended on To a dried glass tube was added phenol solution (0.3mmol, 0.3 mL, 1 M in CH 2 Cl 2 ), gold catalyst (0.01 mmol, 0.01 M in CH 2 Cl 2 ), which was preformed prior to be used. Subsequently, CH 2 Cl 2 was added, keeping the reaction volume is equal to 3.8 mL. The reaction was cooled to -20 o C and diazo (0.2 mmol, 0.2 mL solution in CH 2 Cl 2 ) was added and stirred at -20 o C. The reaction was quenched with diluted Et 3 N solution in acetone at different time. Subsequently, dodecane (7.8 mg, 10 μL) was added as internal standard. The reaction mixture was monitored by GC-MS.
From the figure above, the more bulky ligand (2,4-t-BuC 6 H 4 O) 3 P exhibited lower reaction rate than smaller ligand (PhO) 3 P at -20 o C, which cannot be observed at room temperature due to the fast rates of the two reactions. These results supported our proposed mechanism that water severed as proton shuttle and the ligand oxygen was important for stabilizing transition state  through H-bond. The lower rate of (2,4-t-BuC 6 H 4 O) 3 P was attributed to the worse H-bond due to the steric hindrance.

Figure S1
Calculated reaction pathways of diazoacetates and gold catalysts (PhO) 3 PAuSbF 6 and Ph 3 PAuSbF 6 , denoted by the red and black lines respectively, to generate the products N 2 and Aucarbenes.