Substitution of fluorine in M[C6F5BF3] with organolithium compounds: distinctions between O- and N-nucleophiles

Borates M[C6F5BF3] (M = K, Li, Bu4N) react with organolithium compounds, RLi (R = Me, Bu, Ph), in 1,2-dimethoxyethane or diglyme to give M[4-RC6F4BF3] and M[2-RC6F4BF3]. When R is Me or Bu, the nucleophilic substitution of the fluorine atom at the para position to boron is the predominant route. When R = Ph, the ratio M[4-RC6F4BF3]/M[2-RC6F4BF3] is ca. 1:1. Substitution of the fluorine atom at the ortho position to boron is solely caused by the coordination of RLi via the lithium atom with the fluorine atoms of the BF3 group. This differs from the previously reported substitution in K[C6F5BF3] by O- and N-nucleophiles that did not produce K[2-NuC6F4BF3].

However, practical application of this route requires the corresponding starting substances Ar F X, which in many cases are expensive. An alternative approach is based on modification of easily available potassium pentafluorophenyltrifluoroborate (1-K) and we carried out systematic research in this field. Thus, K[C 6 F 5 BF 3 ] was converted into K[2,3,4,5-C 6 HF 4 BF 3 ] using NiCl 2 ·6H 2 O and Zn in the presence of bpy in aprotic polar solvents (DMF, DMA or NMP) [30]. At present the main direction is the study of the substitution of aromatically bonded fluorine atoms in K[C 6 F 5 BF 3 ] with nucleophiles of different nature. The salts K[4-ROC 6 F 4 BF 3 ] (R = Me, Et, Pr, iPr, Bu, t-Bu, PhCH 2 , CH 2 =CHCH 2 , Ph) were prepared by alkoxydefluorination of K[C 6 F 5 BF 3 ] with the corresponding O-nucleophiles RONa or ROK [31]. The nucleophilic substitution of a fluorine atom in K[C 6 F 5 BF 3 ] with sodium (potassium) azolides in polar aprotic solvent (DMF, DMSO) at 100-130 °C resulted in K[4-R 2 NC 6 F 4 BF 3 ] (R 2 N = pyrrolyl, pyrazolyl, imidazolyl, indolyl, and benzimidazolyl) with 74-93% isolated yield. In contrast, sodium morpholinide and sodium diethylamide did not react with K[C 6 F 5 BF 3 ] under the same conditions. The attempted preparation of K[4-R 2 NC 6 F 4 BF 3 ] (R 2 N = morpholinyl, Et 2 N) using an excess of dialkylamine as well as morpholine and K 2 CO 3 leads to C 6 F 5 H and dialkylaminotetrafluorobenzene [32]. Additional experiments on the competitive nucleophilic substitution of 2,3,4,5,6-pentafluorobiphenyl (model substrate) with sodium indolide and sodium morpholinide (DMF, 130 °C, 4 h) showed the kinetic reason of this phenomenon: the first nucleophile reacts with the substrate much faster than the second one. In the case of K[C 6 F 5 BF 3 ] this leads to the formation of C 6 F 5 H (byproduct) rather than the formation of K[4-R 2 NC 6 F 4 BF 3 ] due very slow aminodefluorination with NaNR 2 [32].
Being interested in a wide series of polyfluoroaryltrifluoroborates, we investigated possible reaction routes from M[C 6 F 5 BF 3 ] (M = K, Li and Bu 4 N) to alkyl-, alkynyl-and aryltetrafluorophenyltrifluoroborates using the nucleophilic substi-tution with some organolithium compounds. The obtained results were compared with previously reported data [31,32].

Reactions with MeLi
An addition of MeLi (1.5 equiv) in ether to a solution of K[C 6 F 5 BF 3 ] (1-K) in DME causes precipitation of a white solid. Stirring of the suspension at 22 °C for 3 h with subsequent treatment with aqueous KF gave potassium 4-methyltetrafluorophenyltrifluoroborate, K[4-MeC 6 F 4 BF 3 ] (2-K) and potassium 2-methyltetrafluorophenyltrifluoroborate, K[2-MeC 6 F 4 BF 3 ] (3-K) (1:0.13) besides unreacted 1-K (total conversion 51%) ( Table 1, entry 1). A prolongation of the reaction time up to 6 h has no effect on composition of products (Table 1, entry 2). In the presence of a large excess of the nucleophile (2.5 equiv of MeLi) conversion of 1-K increases up to 85% (Table 1, entry 3) and 100% (3.6 equiv of MeLi) ( Table 1, entry 4). When the reaction was performed at 43-47 °C for 3 h, the conversion of 1-K was 83%, but the yield of borate 2-K was lower because of side reactions (mainly, hydrodeboration) ( Table 1, entry 5). The reflux of 1-K with 2.0 equiv of MeLi in DME-ether for 5 h gave 2-K and 3-K besides a small quantity of 1-K (Table 1, entry 6) (Scheme 2). The use of 3.9 equiv of the nucleophile and reflux of the suspension for 1 h led to the total consumption of 1-K but the desired aryltrifluoroborates were not obtained. Instead, a mixture of many unknown products forms in which a small amount 2,3,5,6-tetrafluorotoluene (4) was identified. Treatment of these products with aqueous KF increased the content of 4 and led to the appearance of C 6 F 5 H and 2,3,4,5-tetrafluorotoluene (5) ( 19 F NMR), which may be attributed to hydrodeboration of unrecognized arylboron compounds.

Reactions with BuLi
In general, reactions of 1-K with BuLi proceed as reactions with MeLi although the precipitation was not observed. The reaction of BuLi (2 equiv) with 1-K in DME-hexanes at 22 °C for 2 h and the subsequent treatment of the reaction mixture with aqueous KF gave potassium 4-butyltetrafluorophenyltri-  fluoroborate (6-K) and potassium 2-butyltetrafluorophenyltrifluoroborate (7-K) (molar ratio 1:0.18) ( Table 2, entry 1). In the presence of a larger excess of BuLi the quantity of 7-K reduced to 1:0.10, presumably because of further substitution ( Table 2, entry 2). Heating the reaction mixture at 55-60 °C for 1 h leads to substitution of two fluorine atoms with the formation of potassium 2,5-dibutyltrifluorophenyltrifluoroborate (8) and potassium 2,4-dibutyltrifluorophenyltrifluoroborate (9) (minor) besides 6-K and 7-K (major) ( Table 2,

Reactions with PhLi
The addition of PhLi in ether to a solution of 1-K in DME leads to the formation of a precipitate similar to that in the reaction with MeLi. Contrary to the nucleophilic alkylation, the use of equimolar amounts of phenyllithium leads to complete consumption of 1-K and the formation of potassium 4-phenyltetrafluorophenyltrifluoroborate (10-K), potassium 2-phenyltetrafluorophenyltrifluoroborate (11-K) and admixtures of potas-  sium 2,5-diphenyltrifluorophenyltrifluoroborate (12-K) and potassium 2,4-diphenyltrifluorophenyltrifluoroborate (13-K) ( Table 3, entry 1). The reaction of 1-K with a subequimolar amount of phenyllithium (0.8 equiv) in DME-ether at 22 °C for 2 h gave a mixture of starting borate, and small amounts of 10-K and 11-K (Table 3, entry 2). Prolongation of the reaction time up to 6 h increases yields of 10-K and 11-K but 1-K remains a predominant component (Table 3, entry 3). When 1-K reacts with a three-fold excess of PhLi, the yields of monoarylated borates 10-K and 11-K become equal to that of diarylated borates 12-K and 13-K (Table 3, entry 4). In the presence of large excess of nucleophile borates 12-K and 13-K are the main products while compounds 10-K and 11-K were present in trace amounts (Table 3, entry 5, Scheme 4). Some unknown by-products were also formed.
When 1-K reacts with an excess of PhLi (1.6 equiv) at 37-40 °C for 1 h, the supernatant after treatment with aqueous KF contains 10-K and 11-K besides traces of 1-K and 13-K (

Reactions with PhC≡CLi
Attempts to involve 1-K in the reaction with PhC≡CLi failed. Stirring the reagents in DME-ether solution at 22 °C for 17 h leads to recovery of borate 1-K. The same result was obtained at 40 °C (2 h) and under reflux (58 °C, bath) for 5 h. It should be noted that in all cases 1-K was recovered unchanged, e.g., no side reactions occurred.
In addition to identifying the reaction products by NMR spectroscopy, we confirmed their constitution by using the hydrodeboration reaction. This method consists in replacement of the BF 3 group in polyfluoroaryltrifluoroborates by hydrogen in alcohol at elevated temperature and obtaining the corresponding polyfluoroarenes in high yields. The latter are more simple substances and available for analysis by NMR spectroscopy, GC-MS and HRMS methods [33]. Heating a mixture of 6-K, 7-K, 8-K and 9-K in MeOH leads to conversion of these salts to 16, 17, 18 and 19, respectively. The molar ratio of the produced polyfluoroarenes is the same as the ratio of their organoboron precursors (Scheme 5).
The 19 F NMR spectrum of 17 was described [34] and the spectrum of 16 is closely related to the spectrum of known compound 4 [33]. Then a mixture of borates 10-K, 11-K, 12-K, and 13-K was converted to biphenyls 14, 15, and terphenyls 20, 21, respectively, and characterized by 19 F NMR spectroscopy, GC-MS and HRMS (Scheme 7).

Discussion
Above we mentioned that an addition of MeLi or PhLi in ether to a solution of 1-K in DME caused immediate precipitation.  In the course of these experiments we paid attention on distinctions in the NMR spectra of M[C 6 F 5 BF 3 ] (M = Li, K, Bu 4 N) ( Table 4).
The replacement of Li + by K + and Bu 4 N + is accompanied with remarkable changes in the NMR spectra. In the 11   investigations in this field are out of the scope of the current research but some qualitative considerations may be outlined. In solution of 1-Li in DME the lithium cation is strongly coordinated with one or multiple fluorine atoms bonded to boron ("hard"-"hard" interaction) and with solvent molecules to form contact ion pair [37]. The opposite situation is in 1-N where the bulky tetrabutylammonium cation ("soft") interacts with those fluorine atom(s) weaker than Li + either in DME and diglyme and this salt forms solvent-separated ion pairs. Potassium pentafluorophenyltrifluoroborate is the intermediate position.   (Table 3, entries 2, 3 and 6). Other data from Table 3 are not reliable for comparison because the initial ratio is remarkably corrupted by the further reactions. We believe that the enrichment of the reaction mixture in [2-PhC 6 F 4 BF 3 ] − occurs because of an additional stabilization of transition state A (Scheme 9) due to the π-stacking interactions between C 6 H 5 and C 6 F 5 moieties (Scheme 10), which is excluded in cases of nucleophilic alkylation.
In our opinion, the reason of the negligible content of isomer [2-NuC 6 F 4 BF 3 ] − is the lesser affinity to fluoride of Na + and K + compared with Li + (considerations on the relative fluoride affinities are grounded on the crystal lattice energy of LiF (1027 kJ·mol −1 ), NaF (914 kJ·mol −1 ) and KF (812 kJ·mol −1 ) [38]) and the ionic nature of RO-M and RR'N-M (M = K, Na) bonds in the examined nucleophiles. Even in spite of the possible coordination of K + or Na + with the BF 3 group, free anions RO − or RR'N − attack the carbon atom C-4 rather than C-2 and C-6.
When pentafluorophenyltrifluoroborates react with MeLi (Table 1, entries 5 and 6) or PhLi ( Presumably, one role of lithium halides is the fluoride abstraction from lithium aryltrifluoroborate (or significant polarization of the B-F bond) and the subsequent hydrodeboration of aryldifluoroborane by residual moisture in the solvent (Scheme 13).  3 ] in CH 2 Cl 2 ), such migration of − OMe and its subsequent elimination is hindered [42]. In the case of pentafluorophenyltrifluoroborates the similar conversion does not occur even with Li[C 6 F 5 BF 3 ] in DME (contact ion pairs) due to the higher Lewis acidity of C 6 F 5 BF 2 relative to C 6 F 5 B(OMe) 2 , which prevents the formation of fluoro-bridged intermediates such as B. 4. The formation of M[2-RC 6 F 4 BF 3 ] proceeds through the coordination of RLi (polarized C-Li bond) to a fluorine atom of the BF 3 moiety and subsequent elimination of LiF. In contrary, the cation-anion bonds in O-nucleophiles and in N-nucleophiles are ionic (M = K, Na) and the fluoride affinities of K + and Na + are smaller than that of Li + . These factors determine the reaction route with K[C 6 F 5 BF 3 ] by a simple S N 2 mechanism.

Supporting Information
Supporting Information File 1 Full experimental details and compounds characterization data.