Applying Na/Co(ii) bimetallic partnerships to promote multiple Co–H exchanges in polyfluoroarenes

Heterobimetallic base NaCo(HMDS)3 [HMDS = N(SiMe3)2] enables regioselective di-cobaltation of activated polyfluoroarenes under mild reaction conditions. For 1,3,5-C6H2X3 (X= Cl, F), NaCo(HMDS)3 in excess at 80 °C impressively induces the collective cleavage of five bonds (two C–H and three C–X) of the substrates via a cascade activation process that cannot be replicated by LiCo(HMDS)3 or KCo(HMDS)3.


General considerations
All reactions were carried out under an inert dry argon atmosphere utilising standard Schlenk line and glove-box techniques (MBraun, MB10 Compact or UniLab Pro, <0.5 ppm H2O, O2). Na(HMDS) was purchased from Sigma Aldrich and used as received.
Co(HMDS)2 and [NaCo(HMDS)3] (1) were prepared according to a modified literature procedure from Lappert et al. and Layfield et al. respectively. [1][2] Hexane, toluene, benzene and pentane were dried prior to synthesis by Grubbs column 3 (MBraun SPS 5) to remove any traces of moisture and dissolved oxygen and then further dried by stirring over NaK2.8 overnight before vacuum transferring and subsequently storing over 4 Å molecular sieves.
Deuterated solvents C6D6, d8-toluene and d8-THF for NMR spectroscopy were dried over NaK2.8, vacuum transferred and stored over 4 Å molecular sieves in the glove-box prior to use. All NMR spectroscopy samples were prepared inside the inert argon atmosphere of the glove-box. 1 H (300.13 MHz), NMR spectra were recorded on a Bruker Avance III HD 300 spectrometer at 300 K and analysed using TopSpin (v4.0.5, Bruker Biospin, Karlsruhe). NMR spectra were referenced internally to the corresponding residual protio solvent peaks.
The paramagnetic nature of the Co(II) compounds here reported precludes the acquisition of 19 F and 13 C spectra. In particular, no resonances could be observed in the 19 F{1H} (376.40 MHz) between 500 and −500 ppm and this is likely due to very rapid relaxation of the 19 F nuclei. 4 Solution magnetic susceptibilities were determined by the Evans method at 300 K. 5 CHN elemental microanalyses were performed on a Flash 2000 Organic Elemental Analyser (Thermo Scientific).

Synthesis of numbered compounds
[NaCo(HMDS)2(C6F2H3)] (2) 0.189 g (0.5 mmol) of Co(HMDS)2 and 0.092 g (0.5 mmol) of Na(HMDS) were dissolved in 10 ml of hexane and the bright green solution was left to stir for one hour before removing all solvent under vacuum. The light green solid was redissolved in 5 ml of benzene to which 0.024 ml (0.25 mmol) of 1,4-difluorobenzene were added. The green solution was stirred for 1 h at 80 °C resulting a darkening of the initial colour. Dark green crystals were obtained from a hexane/THF solution, isolated, washed with cold hexane and dried (0.073 g, 56 % yield).

[Na2Co2(C6F3H)(HMDS)4] (3)
0.189 g (0.5 mmol) of Co(HMDS)2 and 0.092 g (0.5 mmol) of Na(HMDS) were dissolved in 10 ml of hexane and the bright green solution was left to stir for one hour before removing all solvent under vacuum. The light green solid was redissolved in 5 ml of benzene to which 0.026 ml (0.25 mmol) of 1,3,5-trifluorobenzene were added. The green solution was stirred for 1 h at 80 °C. Dark green crystals were obtained from a hexane/THF solution, isolated, washed with cold hexane and dried (0.053 g, 33 % yield). 0.189 g (0.5 mmol) of Co(HMDS)2 and 0.092 g (0.5 mmol) of NaHMDS were dissolved in 10 ml of hexane and the bright green solution was left to stir for one hour before removing all solvent under vacuum. The light green solid was redissolved in 5 ml of benzene to which 0.028 ml (0.25 mmol) of 1,2,4,5tetrafluorobenzene were added forming a dark green solution with a light green precipitate. THF was added dropwise to get an almost clear dark green solution which was heated gently and left to slowly cool down to room temperature. Green crystals were isolated, washed with cold hexane and dried (0.148 g, 62 % yield).

NMR Studies/ Supplementary Experiments
Stepwise dimetalation of 1,2,4,5-tetrafluorobenzene: In a J. Young's NMR tube 1,3,5-tetrafluorobenzene (0.1 mmol, 11 L) was added to d8-Tol and the solution cooled to 0 °C. NaCo(HMDS)3 (1) (0.1 mmol, 0.056 g) was added, resulting in the formation of a dark green solution. The reaction was monitored by 1 H NMR spectroscopy, which revealed immediate reaction between the two species to form 5 (two broad signals at 42.60 and −15.68 ppm). Whilst still at 0 °C, a second equivalent of 1 (0.1 mmol, 0.056 g) was added. No change in colour was observed, although 1 H NMR showed the disappearance of the peaks of 5 together with the appearance of a new signal at −4.17 which can be attributed to compound 4.

Conversion of 1,4-difluorobenzene to 2:
In a J. Young's NMR tube 1,4-difluorobenzene (0.1 mmol, 10 L) was added together with a constant amount of Hexamethylbenzene as internal standard and dissolved in 0.5 mL of C6D6. An initial 1 H NMR was recorded. To the clear solution 2 eq. of NaCo(HMDS)3 (1) (0.2 mmol, 0.112 g) was added to obtain a light green solution. After heating for 1 hour at 80 °C a second 1

Solution Magnetic Moments Susceptibilities
General method: In a J. Young's NMR tube, the respective compounds were accurately weighted and the initial mass noted. 0.5 ml of deuterated solvent (C6D6 for compounds 2,3,4,7 and 8 and d8-Tol for compound 5) was added and the final mass noted. To the clear solution, a sealed capillary containing a mixture of proteo and deuterated solvent (1:50 ratio) was added and 1 H NMR spectra recorded on a Bruker Avance III HD 300 spectrometer at 300 K. The effective magnetic moment was calculated considering the peak separation (Δf) of the solvent resonance between that of pure solvent (in the capillary) and that shifted by the paramagnet (outside of the capillary). This can be calculated in ppm and converted into Hz using Eq. 1.1. The magnetic susceptibility and the magnetic moment can then be calculated using Eq. 1.2.
For each compound, the measurement was repeated three times and the effective magnetic moment (μeff) calculated as average of the calculated values. In brackets, the standard deviation. (see TableS2). Effective magnetic moment calculations: Table S2. Effective magnetic moment calculations for compounds 2-5,7-8.
Note = The magnetic moments of compounds 3, 4 and 7 can be explained by the presence of two distorted trigonal high spin Co(II) centres (S = 3/2). The overall slightly higher spin only value from an ideal value of 5.47 μB (calculated considering Spin only value for one Co(II) (S = 3/2) being 3.87 μB and the total (spin only) moment for compounds with two Co centres being 3.87 x ⱱ2 = 5.47 μB) can be due to small SOC (spin orbit coupling) contribution. Although, it can not be excluded the presence of weak ferromagnetic coupling between the two metal centres occurring through the aromatic ring.

X-Ray Crystallographic Figures and Data
The crystal structures of compounds 2, 3, 4, 7 and 8 have been deposited into the Cambridge Crystallographic Data Centre (CCDC) and have been assigned the following numbers: 2247797-2247801. Selected crystallographic and refinement parameters are presented in Tables S4, S5 and S6 below. In all cases samples immersed in inert oil were mounted at ambient conditions and transferred into the cold stream of nitrogen.
The structures of compounds 2, 3, 4, 7 and 8 were measured at the University of Bern, Switzerland. All measurements were performed on either a RIGAKU Synergy S or Oxford Diffraction SuperNova area-detector diffractometer using mirror optics monochromated Cu Kα radiation (λ = 1.54184 Å) or Mo Kα radiation (λ = 0.71073 Å), respectively. Data reduction was performed using the CrysAlisPro program. 7 The structure was solved by direct methods using SHELXT, 8 which revealed the positions of all non-hydrogen atoms of the title compound. Refinement of the structure was carried out on F2 using full-matrix least-squares procedures. All calculations were performed using the SHELXL-2014/7 program in Olex2. 8