Transmetalation Reactions Triggered by Electron Transfer between Organocopper Complexes

[Cu(bipy)(C6F5)] reacts with most aryl iodides to form heterobiphenyls by cross-coupling, but when Rf–I is used (Rf = 3,5-dicholoro-2,4,6-trifluorophenyl), homocoupling products are also formed. Kinetic studies suggest that, for the homocoupling reaction, a mechanism based on transmetalation from [Cu(bipy)(C6F5)] to Cu(III) intermediates formed in the oxidative addition step is at work. Density functional theory calculations show that the interaction between these Cu(III) species and the starting Cu(I) complex involves a Cu(I)–Cu(III) electron transfer concerted with the formation of an iodine bridge between the metals and that a fast transmetalation takes place in a dimer in a triplet state between two Cu(II) units.


S1. General methods and reagent availability
All the manipulations were performed under N2 atmosphere, using standard Schlenk techniques. Solvents were dried using a solvent purification system SPS-MD5 or distilled from appropriate drying agents under nitrogen according to literature, 1 and storing them over 3 Å zeolites for a week. Prior to its use, solvents were degassed by three freeze-pump-thaw cycles. NMR spectra were recorded on Bruker AV 400 or Varian Inova 500-MR instruments equipped with variable-temperature probes. All glassware was flame dried or dried overnight at 110 ºC and allowed to cool under vacuum. Chemical shifts are reported in ppm from tetramethylsilane ( 1 H and 13 C), CCl3F ( 19 F), with positive shifts downfield, at 298 K unless otherwise stated. The temperature for the NMR probe was calibrated with a methanol standard. 2 For the 19 F NMR spectra registered in nondeuterated solvents, an internal coaxial tube containing acetone-d6 was used to maintain the lock 2 H signal.
Numbering of the complexes:

Synthesis of (NBu 4 )[Cu(C 6 F 5 ) 2 ]
C6F5Br (555 μL, 4.45 mmol) was charged in a 100 mL Schlenk flask protected from the light. Et2O (17 mL) was added and the solution was cooled to -60 ºC in a isopropanol bath cooled using a cryostator. Then, a solution of BuLi 1.6M in hexanes (2.72 mL, 4.35 mmol) was added and the mixture was stirred for 45 min. Freshly prepared (NBu4)[CuCl2] (800 mg, 2.12 mmol) was then added and the temperature warmed to -40 ºC, the mixture was stirred during 4 h. After that, the bath was allowed to warm during another hour, at that moment the mixture is a light yellowish suspension. Solvents were removed under vacuum and the solid residue was stirred with 18 mL of CH2Cl2, then, solids were separated by filtering through Celite using a Schlenk frit and rinsed with To study the effect of the electronic properties of the aryl iodides in the oxidative addition reaction to compound 1, several competitive experiments containing parasubstituted aryl iodides along with iodobenzene were carried out.
Yields for the pentafluorophenylation reaction of each aryl iodide were derived from 19 F NMR spectra performed after the heating time, taking into account the amount of each aryl iodide added and the loss of reagent 1 due to the hydrolysis reaction with water traces. Relative reaction rates for each aryl iodide respect to the one of iodobenzene could be calculated and plotted against the Hammet parameters. (Figure 1 in main text) Kinetic independent constants for each aryl iodide were calculated by comparison with the measured value for iodobenzene. Table S1: Values of coupling constants for the reaction of aryl iodides 9a-9g with complex 1 in THF at 50 ºC.
Ar-I 9a 9b 9c 9d 9e 9f 9g k / s -1 ·M -1 2.23·10 -3 1.36·10 -3 1.32·10 -3 4.04·10 -4 2.10·10 -4 1.59·10 -4 1.50·10 -4 It has been reported that pentafluorophenylated Cu(I) complexes react with residual O2 traces present in the media to yield the homocoupling product C6F5-C6F5. 12 However, the formation of C6F5-C6F5 could also be attributed to some other reactivity desrived from the interaction of complex 1 with the aryl halides. To rule out this possibility for the nonperhalogenated aryl halides, compound 1 was let react in the absence of aryl iodides and in the same conditions as in the competitive experiments. This reaction yielded a much higher amount of the coupling product C6F5-C6F5 that the observed in the competitive experiments. These results imply that, in absence of aryl iodides, complex 1 reacts with both H2O and O2 impurities present in the medium being the latter reaction much slower. Once the water has been consumed, the remaining concentration of complex 1 is still high compared to the one in competitive experiments and O2 can keep reacting with 1 to yield compound C6F5-C6F5.
µL, 0.105 mmol) were placed inside a screwed cap NMR tube with the aid of a Schlenk NMR tube adaptor, then, 1.47 mL of a freshly prepared stock solution containing 1 (0.072 M) and 4,4'-difluorobiphenyl (0.0044 M) in THF were added. Finally, a flame sealed coaxial capillary containing acetone-d6 was added and the tube was closed and manually shaken until dissolution of solids. The tubes were heated at 50 ºC for 12h in an oil bath. S12 S5. 19

F NMR monitoring of the reaction between compound 1 and C6Cl2F3I
Monitoring of the reactions of compound 1 with C 6 Cl 2 F 3 I Weighted amounts of complex 1 were added inside a screw cap NMR tube with the aid of a Schlenk NMR tube adaptor along with a flame sealed coaxial capillary containing acetone-d6 to keep the lock signal. The tube was cooled to -75 ºC in an isopropanol bath and a weighted amount of 4,4'difluorobiphenyl, THF and a weighted amount of C6Cl2F3I were added. The tube was closed inside the adaptor and then, taken out of the cool bath, manually shaken until total dissolution of solids and transferred to the NMR probe, which had been preheated to the monitoring temperature (25 ºC). Recording started after about 2 min required for the setup of the experiment, time zero for the measurements is taken at that moment. 19 F NMR spectra parameters are 64 scans, relaxation delay of 1 s, pulse angle of 30º, spectral width of 48076. 9 Hz, and size of 32768 points. Spectra were collected every 300 s.
Values of concentration vs time were obtained by integration of 19 F NMR signals relative to the internal standard, 4,4'difluorobiphenyl. These values had to be corrected to compensate the different relaxation times of nuclei in different substances by applying a correction factor. Correction factors were obtained by measuring the integral of 19 F NMR experiments performed in the exact same conditions of the monitoring of samples containing mixtures of 4,4'difluorobiphenyl as internal standard and accurately weighted amounts of (NBu4)[Cu(C6F5)2], C6Cl2F3I, C6F5I, C6Cl2F3H, C6F5H, C6Cl2F3-C6Cl2F3, C6F5-C6F5, [Cu(bipy)(C6F5)] and [Cu(bipy)(C6Cl2F3)]. The correction factor for the product C6Cl2F3-C6F5 was estimated as the average of the homocoupling products.

S6. Control experiments
To test the capability of species [Cu(C6F5)2]to undergo oxidative addition reaction with aryl iodides, the reaction of compound (NBu4)[Cu(C6F5)2] 2 with PhI was monitorized in the same conditions as in the reaction of compound 1 (See S4). After 6.7 h, coupling product C6F5-Ph was formed only in trace amounts >1%.
Also, the potential of species [Cu(bipy)I] and [Cu(bipy)2] + to undergo oxidative addition reaction with aryl iodides was evaluated by letting the complexes [Cu(bipy)I] and [Cu(bipy)2]BF4 react with C6F5I in the same reaction conditions as in the monitoring experiments of the reaction between 1 and C6Cl2F3I (See S5) for 4 h. No coupling products containing the moiety C6F5 were detected.
To assess that the behavior of the system does not depend on the electronic properties of the complexes containing similar yet different aryl moieties, complex [Cu(bipy)(C6Cl2F3)] 4 was synthesized and its reaction with C6F5I in THF at 25 ºC was monitored by 19 F NMR. Initial concentration of the reactants for this experiment differ from the used in the monitorization of the reaction of 1 and C6Cl2F3I due to solubility problems (See S5). Again, the formation of the homocoupling product C6Cl2F3-C6Cl2F3 containing the group that initially forms the organometallic reactant, shows a much higher rate of formation at the beginning of the reaction course than C6F5-C6F5.

Experimental procedures for control experiments
Monitoring of the reaction of compound 4 with C 6 F 5 I Complex 4 (2.35 mg, 0.006 mmol) was added inside a screw cap NMR tube with the aid of a Schlenk NMR tube adaptor along with a flame sealed coaxial capillary containing acetone-d6 to keep the lock signal. The tube was cooled to -75 ºC in an isopropanol bath and a weighted amount of 4,4'difluorobiphenyl (0.45 mg, 0.002 mmol), THF (0.96 mL) and C6F5I (1.5 µL, 0.011 mmol) were added. The tube was closed inside the adaptor and then, taken out of the cool bath, manually shaken until total dissolution of solids and transferred to the NMR probe, which had been preheated to the monitoring temperature (25 ºC). The 19 F NMR recording started after about 2 min used for the setup of the experiment, time zero for the measurements is taken at that moment.

Monitoring of the reaction of Compound 2 with PhI
Complex 2 (25.60 mg, 0.040 mmol) was added inside a screw cap NMR tube with the aid of a Schlenk NMR tube adaptor along with a flame sealed coaxial capillary containing acetone-d6 to keep the lock signal. The tube was cooled to -75 ºC in an isopropanol bath and a weighted amount of 4,4'difluorobiphenyl (2.50 mg, 0.013 mmol), THF (0.54 mL) and PhI (27 µL, 0.241 mmol) were added. The tube was closed inside the adaptor and then, taken out of the cool bath, manually shaken until total dissolution of solids and transferred to the NMR probe, which had been preheated to the monitoring temperature (50 ºC). The 19 F NMR recording started after about 2 min used for the setup of the experiment. After 6.6 h the conversion of complex 2 in C6F5-Ph was lower than 2%.

Reaction of [Cu(bipy)I] and [Cu(bipy) 2 ]BF 4 with C 6 F 5 I
Compounds [Cu(bipy)I] (50 mg, 0.142 mmol) or [Cu(bipy)2]BF4 (65 mg, 0.142 mmol) were added inside a 5 mL Schlenk flask along with a magnetic stir bar. Three vacuum/N2 cycles were performed, then, C6F5I (18.9 µL, 0.142 mmol) and THF (2.00 mL) were added under nitrogen countercurrent. The flask was closed under nitrogen pressure and the red suspension was stirred for 4 h at room temperature. After that, the suspension was decanted and an aliquot of 0.5 mL was transferred inside an NMR with the aid of a Schlenk NMR tube adaptor along with a flame sealed coaxial capillary containing acetone-d6 to keep the lock signal. The tube was closed inside the adaptor and transferred to the spectrometer to acquire a 19 F NMR spectrum.

S7-1. Determination of the kinetic order of reaction of compound 1 in oxidative addition reactions with perhaloaryl iodides
Monitoring of the reactions of compound 1 with C 6 F 5 I Weighted amounts of complex 1 were added inside a screw cap NMR tube with the aid of a Schlenk NMR tube adaptor along with a flame sealed coaxial capillary containing acetone-d6 to keep the lock deuterium signal. The tube was cooled to -75 ºC in an isopropanol bath and a weighted amount of 4,4'difluorobiphenyl, THF and a volume of C6F5I taken with a microsyringe. The tube was closed inside the adaptor and then, taken out of the cool bath, manually shaken until total dissolution of solids and transferred to the NMR probe, which had been preheated to the monitoring temperature (25 ºC). 1.7·10 -2 3.6·10 -1 9.6·10 -5 5 1.3·10 -2 3.6·10 -1 8.1·10 -5 Figure S5: Experimental values of initial reaction rates and initial concentrations of compound 1 and plot of Ln(r0) versus Ln(C0). The slope of the straight line is the kinetic order of the reaction on complex 1.

S7-2. Kinetic models used for non-linear fitting of the concentration / time data of the reaction between compounds 1 and C6Cl2F3I
Complex 1 reacts with C6Cl2F3I in THF at 25 ºC producing the cross-coupling product C6Cl2F3-C6F5, the homocoupling biaryls C6F5-C6F5 and C6Cl2F3-C6Cl2F3 and residual amounts of the hydrolysis products C6F5H and C6Cl2F3H (Scheme S3).
Scheme S3: Detected products in the reaction of 1 and C6Cl2F3I in THF at 25 ºC.
We have hypothesized two possible routes for the formation of the homocoupling products, in both of them the equilibrium of formation of the cuprate and the hydrolysis reactions have been taken into account. The model I includes consecutive oxidativeaddition / reductive elimination equilibria leading to the aryl exchange process (Scheme S4). In this mechanism the formation of C6F5I and the complex [Cu(bipy)(C6Cl2F3)] (4) are merely the consequence of the reversibility of the oxidative addition step. The accumulation in solution of C6F5I enables the formation of the homocoupling product C6F5-C6F5 by reacting with the abundant complex 1 and the accumulation of [Cu(bipy)(C6Cl2F3)] (4) accounts for the formation of the homocoupling product C6Cl2F3-C6Cl2F3 by reacting with the aryl halide C6Cl2F3I which is used in large excess.
[ The second mechanism (model II) assumes as possible transmetalation reactions involving copper(I) and copper(III) complexes. Scheme S5 shows two possible pathways for the formation of C6F5-C6F5. In pathway "a" the transmetalation produces the exchange of aryls between Cu(I) and  Figure 1 in the main text shows the experimental concentration time plot of the formation of C6Cl2F3-C6Cl2F3 and C6F5-C6F5 and the best fitting for both models. In both models the fitting of the formation of C6Cl2F3-C6Cl2F3 is quite good although model II fits better at long reaction times. That is the expected result because in both models C6Cl2F3-C6Cl2F3 requires the accumulation of 4 to take place. However, the models and the fitting differ substantially about the formation of C6F5-C6F5 (in blue in figure 1 main text). In this case the experimental results do not support the requirement of the accumulation of C6F5I which is implicit on model I. On the contrary, the experimental line and the fitting indicates that C6F5-C6F5 is formed independently of [C6F5I], and at high rate since the beginning of the reaction.
The kinetic models were fit to the final concentration / time data by non-linear least squares (NLLS) using the software COPASI. 10

Used models in the non-linear fit with program COPASI
In all the models rate constants kion and kneutro were forced to be related based on the measured value of Kion. Also, values for the initial H2O concentration and hydrolysis kinetic constants k1 and k2 were fitted by the program without restrictions.

Reaction
No restrictions were applied to the kinetic constants for the coupling reactions (Table S4 kcoup 1-4) involving C6F5 or C6Cl2F3 groups in order to get the best fitting. When restrictions due to the similar behavior of C6F5 and C6Cl2F3 groups were imposed (kmet = kmet-1; kcoup1 = kcoup2 = kcoup3 = kcoup4 ) no fitting minimum could be reached.

S23
For the non-linear fitting using both pathways of model II, different complexes bearing groups (C6F5) and (C6Cl2F3) were considered similar in terms of reactivity, 13 and therefore, reactions involving them are computed with the same kinetic constants: kelim for the reductive elimination irreversible reactions from Cu(III) species.
kad-ox and kx-I for the oxidative addition equilibria between aryl iodides and Cu(I) arylated complexes.
ktrans and kretro for the transmetalation equilibria between Cu(I) and Cu(III) complexes.
For model II Pathway b, in the reductive elimination reactions, constant kelim is multiplied for a number representing the statistical probability for that reductive elimination to take place from the starting Cu(III) complex.
Even applying these restrictions, the fitting of model II pathway a is more appropriate than that obtained using model I (see below graphics of the models).

Inconsistencies of the model I:
The best fitting leads to rate constants values that are very different for analogous reactions with C6F5 and C6Cl2F3, contrarily to the experimental observations. 13 Note also the very poor fitting of the points due to [C6F5-C6F5] in all the graphics.

S10. X-ray crystallography: Structure of [Cu(C6F5)2](NBu4)
For the compound C28H36CuF10N, (NBu4)[Cu(C6F5)2] 2, suitable single crystals were obtained by layering hexane in a CH2Cl2 solution of the compound at -32 ºC under nitrogen, the crystal was submerged in immersion oil, attached to a loop and transferred to the diffractometer.
Diffraction data for the crystal were recorded in an Oxford Diffraction Super Nova diffractometer with an Atlas CCD area detector. The crystal was kept at 210 K during data collection. Data collection was performed with Mo-Kα radiation (l = 0.71073 Å). Data integration, scaling and empirical absorption correction was carried out using the CrysAlis Pro program package. 14 The structure was solved using the programs Olex2. 15 The non-hydrogen atoms were refined anisotropically and hydrogen atoms were placed at idealized positions and refined using the riding model. Refinement proceeded smoothly to give the residuals shown in

S11. Computational Details
Theoretical calculations were performed at DFT level of theory using Gaussian16 software. 16 The structures of all the intermediates and transition states were optimized in tetrahydrofuran solvent (THF, e= 7.4257) with the SMD continuum model 17 using the B3LYP functional 18 combined with the Grimme's D3 correction for dispersion. 19 Additional calibration calculations employing a set of functionals were carried out for certain structures (see section S16 in the Supporting Information). Basis set BS1 was used for the optimizations. BS1 includes the 6-31G(d,p) basis set for the main group elements, 20 excluding iodine, and the scalar relativistic Stuttgart-Dresden SDD pseudopotential and its associated double-z basis set, 21 complemented with a set polarization functions, for the copper (f polarization functions) 22 and iodine (d polarization functions) 23 atoms. Frequency calculations were carried out for all the optimized geometries in order to characterize the stationary points as either minima or transition states.
Gibbs energies in tetrahydrofuran were calculated at 298.15 K adding to the potential energies in tetrahydrofuran, obtained with single point calculations using an extended basis set (BS2) at the BS1 optimized geometries, the thermal and entropic corrections obtained with BS1. BS2 consists in the def2-TZVP basis set for the main group elements, and the quadruple-z def2-QZVP basis set for Cu. 24 A correction of 1.9 kcal mol -1 was applied to all Gibbs values to change the standard state from the gas phase (1 atm) to solution (1 M) at 298.15 K. 25 In this way, all the energy values in the energy profiles are Gibbs energies in THF solution calculated using the formula: where ΔG 1atm→1M = 1.9 kcal mol -1 is the Gibbs energy change for compression of 1 mol of an ideal gas from 1 atm to the 1 M solution phase standard state.
To locate the minimum energy crossing points (MECP) between singlet and triplet potential energy surfaces, the program developed by the group of Harvey was employed. 26 To confirm that the MECP connects the two intermediates located in the two energy surfaces, the MECP structure was optimized in the different spin states involved in the crossing. The Gibbs energies in solution of the MECP was estimated by adding to the calculated potential energy of the MECP thermal and entropic corrections calculated with the option freq = projected of the Gaussian 09 program. 27 3D-structures were generated using CYLview. 28

S15. Optimized structures of all the intermediates and transition states in the reaction of [Cu(bipy)Pf] (1) with Ph-I (Gibbs energy
profile in Figure S19) Figure S20. Optimized structures of all the intermediates and transition states in the pathway for the formation of the heterocoupling product, Ph-Pf. In red, relative Gibbs energies in THF, in kcal mol -1 .