Metallation of sensitive fluoroarenes using a potassium TMP-zincate supported by a silyl(bis)amido ligand

Combining a bulky bis(amide) and a reactive one-coordinate TMP (2,2,6,6-tetramethylpiperidide) ligand, a new mixed K/Zn heteroleptic base has been developed for regioselective zincation of fluoroarenes. This special ligand set allows for trapping and structural authentication of the first intermediates of direct Zn–H exchange of fluoroarenes obtained via deprotonative metallation, providing mechanistic insights of the processes involved.


General Methods
All the reactions and manipulation were performed under protective Argon atmosphere; using the standard Schlenk technique or Glovebox MBraun equipped with a gas purification and recirculation unit. Hexane was dried over alumina column of Solvent Purification System (a MBraun MBSPS 5) and stored over activated 4Å molecular sieves collection and under argon atmosphere Tetrahydrofuran were dried over sodium and benzophenone ketyl and purified by distillation under argon atmosphere, after the collection it was stored over activated 4 Å molecular sieves and argon atmosphere. Ph 2 Si(NHAr*) 2 [{Ph 2 Si(NHAr*)(NAr*)K] ∞ were prepared as reported in literature. [1,2] NMR spectra were performed in J. Young's NMR tube, prior oven dried and flushed with argon. NMR spectra were recordered using a Bruker AV 400 spectrometer operating at 400.13 MHz for 1 H and 19 F, 100.62 MHz for 13 C{ 1 H} or a Bruker AV 400 spectrometer operating at 300 MHz for 1 H and 19 F, 75 MHz for 13 C{ 1 H} . 1 H and 13 C{ 1 H} NMR spectra were calibrated against the appropriate solvent signal. All the deuterated solvents for NMR were dried and distilled over NaK 2.8 and stored over activated 4 Å molecular sieves and argon atmosphere.

Synthetic Procedures
Synthesis of ZnTMP 2 2.72 mL of 2,2,6,6-tetramethylpiperidine (16 mmol) were solubilized in 10 mL of THF and then 10 mL of n BuLi solution (1.6 M in hexane) were added drop by drop affording a yellow solution. 1.09 g of ZnCl 2 (8 mmol) were added, instantaneously a white precipitate was formed. The mixture was allowed to stir at room temperature for 1h. All the volatiles were removed under reduced pressure affording a yellow waxy solid. 30 mL of Hexane were added affording a white suspension. The suspension was filtered through celite and the mother liquor was evaporated furnishing Zn(TMP) 2 as white solid (2700 mg 98%). The solid can be further purified via sublimation as reported in the literature. [3]  Synthesis of [{Ph 2 Si(NAr*) 2 Zn(TMP)}¯{K(THF) 6 } + ] (1) 572 mg of freshly prepared [{Ph 2 Si(NHAr*)(NAr*)K] ∞ (I) [2] (1 mmol) and 346 mg of Zn(TMP) 2 (1 mmol) were solubilized in 10 mL of THF and the solution was allowed to stir at reflux overnight. Volatiles (2) 126 mg of KCH 2 SiMe 3 (1mmol), 346 mg of ZnTMP 2 (1mmol) and 10 mL of hexane were added to a flushed Schlenk tube. The white suspension was left stirring for 2 hours until it becomes a fine suspension to which 1 mmol of Ph 2 Si(NHAr*) 2 (530 mg) and 1 mL of THF were added, the yellowish suspension was gently heated and allowed to stir overnight. Volatiles were removed under vacuum and to the white residue 7 mL of hexane and 0.7 mL of THF was added, affording a pale-yellow suspension. The mixture was heated under reflux and let slowly cool down at room temperature depositing a crop of colourless crystals of 2 after 24h at room temperature. (550 mg, yield 76%). The synthesis of this compound can be achieved using a different procedure reported in literature before. [ All the volatiles were removed under reduced pressure. The resulting waxy solid was suspended in 10 mL of hexane and the suspension was filtered through celite. The remaining yellow-white solid was solubilized in 3 mL of hexane and 0.8 mL of THF. Overnight storage in the freezer (-15°C) furnishing yellow crystals of 3h. Any attempt in isolating the pure product was unsuccessful due to the cocrystallization of [K(THF) x Zn(C 6 F 6 ) 3 ] and Ph 2 Si(NHAr*) 2 . The yield determined in NMR scale reaction using hexamethylbenzene as internal standard in 1 H-NMR spectrum was 91%.  to stir at room temperature for 30 minutes. The solution was then left to stir at reflux for 16h. The next day all the volatiles were removed under reduced pressure. The obtained white solid was washed with 6 mL of hexane and solubilized in 2 ml of THF. Layering 1.5 mL of hexane on the yellow solution furnished colourless crystals of 3j (59 mg, 11%). %). The yield determined by 1 H NMR spectroscopy using hexamethylbenzene as an internal standard was 84%.  [5] General Experimental Procedure for the 1

H NMR Monitoring of the Zn-H Exchange Reactions
In a glovebox, a J. Young's NMR tube was filled with 78 mg of 1 (0.1       Adding a three fold excess of pentafluorobenzene 1 exhibits a polybasicity. 3h further reacts through the silyl bis(amido) ligand, generating 4 and Ph 2 Si(NHAr*) 2 (Figure S 7). Notably the reaction did not proceed stepwise and 4 and Ph 2 Si(NHAr*) 2 were generated with almost the same ratio. Pentafluorobenzene is still present in the mixture (Figure S 8   29 -3.098° < θ < 77.579° for 3h. A total of 6512 frames were collected using ω scans, with 0.7 second exposure time (4 s for high-angle reflections), a rotation angle of 0.5° per frame, a crystal-detector distance of 34.0 mm, at T = 100.0(5) K.
Data reduction was performed using the CrysAlisPro program [7] . The intensities were corrected for Lorentz and polarization effects, and an absorption correction based on the multi-scan method using SCALE3 ABSPACK in CrysAlisPro [7] was applied.
The structures were solved by direct methods using SHELXT [8] , which revealed the positions of all nonhydrogen atoms of the title compound. All non-hydrogen atoms were refined anisotropically. H-atoms were assigned in geometrically calculated positions and refined using a riding model where each H-atom was assigned a fixed isotropic displacement parameter with a value equal to 1.2Ueq of its parent atom (1.5Ueq for methyl groups). refinement of the structures was carried out on F 2 using full-matrix least-squares procedures, which minimized the function Σw(F o 2 -F c 2 ) 2 . The weighting scheme was based on counting statistics and included a factor to downweight the intense reflections. All calculations were performed using the SHELXL-2014/7 [9] program in OLEX2.4 [10] The X-ray crystal structure determination service unit of the Department of Chemistry and Biochemistry of the University of Bern is acknowledged for measuring, solving, refining and summarizing the structures of compounds 3b, 3c 3d, 3e, 3h, 3j and 4. The Synergy diffractometer was partially funded by the Swiss National Science Foundation (SNF) within the R'Equip programme (project number 206021_177033).
Selected crystallographic data are presented in Table S1-S4 and full details in cif format can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.uk/data_request/cif