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

Article abstract of DOI:10.3762/bjoc.13.69

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-RC₆F

Full text of DOI:10.3762/bjoc.13.69

Substitution of fluorine in M[C6F5BF3] with organolithium
compounds: distinctions between O- and N-nucleophiles
Anton Yu. Shabalin1,2, Nicolay Yu. Adonin*1,2 and Vadim V. Bardin2,3
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 703–713.
1G.K. Boreskov Institute of Catalysis, SB RAS, Acad. Lavrentjev Ave.
5, Novosibirsk, 630090, Russian Federation, 2Novosibirsk State
University, Pirogova str. 2, Novosibirsk, 630090, Russian Federation
and 3N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, SB
RAS, Acad. Lavrentjev Ave. 9, Novosibirsk, 630090, Russian
Federation
doi:10.3762/bjoc.13.69
Received: 12 December 2016
Accepted: 28 March 2017
Published: 12 April 2017
Associate Editor: V. Gouverneur
Email:
Nicolay Yu. Adonin* - adonin@catalysis.ru
© 2017 Shabalin et al.; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
C-nucleophile; NMR spectroscopy; nucleophilic substitution;
pentafluorophenyltrifluoroborate
Abstract
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. Substitu-
tion 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].
Introduction
Organoborates M[RBX3] (X = OAlk, F) are widely used in tions with C-electrophiles [22-27]. Nowadays a common ap-
various fields of chemistry [1-12]. Their polyfluorinated ana- proach to these compounds is based on the transformation of
logues M[RFBX3] have been used as starting reagents in the polyfluoroarenes under the action of appropriate reagents into
synthesis of compounds of hypervalent bromine [13], iodine the corresponding organometallic derivatives followed by
[14-16] and xenon [17-21]. Over the last 15 years, we reported treating them with suitable boron-containing electrophiles
the successful application of polyfluorinated organoborates (Scheme 1) [28,29]. In order to further expand this powerful
K[RC6F4BF3], K[C6F5B(OMe)3] and K[CF2=CFBF3] as boron- tool for the introduction of polyfluorinated building blocks into
containing reagents in the Pd-catalyzed cross-coupling reac- organic molecules, the synthesis of a series of polyfluoroaryltri-
703

Beilstein J. Org. Chem. 2017, 13, 703–713.
Scheme 1: Preparation of polyfluoroorganotrifluoroborates.
fluoroborates with substituents different from fluorine atoms is tution with some organolithium compounds. The obtained
desirable.
results were compared with previously reported data [31,32].
Results
However, practical application of this route requires the corre-
sponding starting substances ArFX, which in many cases are Reactions with MeLi
expensive. An alternative approach is based on modification of An addition of MeLi (1.5 equiv) in ether to a solution of
easily available potassium pentafluorophenyltrifluoroborate K[C6F5BF3] (1-K) in DME causes precipitation of a white
(1-K) and we carried out systematic research in this field. Thus, solid. Stirring of the suspension at 22 °C for 3 h with subse-
K[C6F5BF3] was converted into K[2,3,4,5-C6HF4BF3] using quent treatment with aqueous KF gave potassium 4-methyltetra-
NiCl2·6H2O and Zn in the presence of bpy in aprotic polar sol- fluorophenyltrifluoroborate, K[4-MeC6F4BF3] (2-K)
vents (DMF, DMA or NMP) [30]. At present the main direc- and potassium 2-methyltetrafluorophenyltrifluoroborate,
tion is the study of the substitution of aromatically bonded fluo- K[2-MeC6F4BF3] (3-K) (1:0.13) besides unreacted 1-K (total
rine atoms in K[C6F5BF3] with nucleophiles of different nature. conversion 51%) (Table 1, entry 1). A prolongation of the reac-
The salts K[4-ROC6F4BF3] (R = Me, Et, Pr, iPr, Bu, t-Bu, tion time up to 6 h has no effect on composition of products
PhCH2, CH2=CHCH2, Ph) were prepared by alkoxydefluorina- (Table 1, entry 2). In the presence of a large excess of the
tion of K[C6F5BF3] with the corresponding O-nucleophiles nucleophile (2.5 equiv of MeLi) conversion of 1-K increases up
RONa or ROK [31]. The nucleophilic substitution of a fluorine to 85% (Table 1, entry 3) and 100% (3.6 equiv of MeLi)
atom in K[C6F5BF3] with sodium (potassium) azolides in polar (Table 1, entry 4). When the reaction was performed at
aprotic solvent (DMF, DMSO) at 100–130 °C resulted in 43–47 °C for 3 h, the conversion of 1-K was 83%, but the yield
K[4-R2NC6F4BF3] (R2N = pyrrolyl, pyrazolyl, imidazolyl, of borate 2-K was lower because of side reactions (mainly,
indolyl, and benzimidazolyl) with 74–93% isolated yield. In hydrodeboration) (Table 1, entry 5). The reflux of 1-K with
contrast, sodium morpholinide and sodium diethylamide did 2.0 equiv of MeLi in DME–ether for 5 h gave 2-K and 3-K
not react with K[C6F5BF3] under the same conditions. besides a small quantity of 1-K (Table 1, entry 6) (Scheme 2).
The attempted preparation of K[4-R2NC6F4BF3]
(R2N = morpholinyl, Et2N) using an excess of dialkylamine as The use of 3.9 equiv of the nucleophile and reflux of the
well as morpholine and K2CO3 leads to C6F5H and dialkyl- suspension for 1 h led to the total consumption of 1-K but the
aminotetrafluorobenzene [32]. Additional experiments on the desired aryltrifluoroborates were not obtained. Instead, a mix-
competitive nucleophilic substitution of 2,3,4,5,6-pentafluoro- ture of many unknown products forms in which a small amount
biphenyl (model substrate) with sodium indolide and sodium 2,3,5,6-tetrafluorotoluene (4) was identified. Treatment of these
morpholinide (DMF, 130 °C, 4 h) showed the kinetic reason of products with aqueous KF increased the content of 4 and led to
this phenomenon: the first nucleophile reacts with the substrate the appearance of C6F5H and 2,3,4,5-tetrafluorotoluene (5)
much faster than the second one. In the case of K[C6F5BF3] this (19F NMR), which may be attributed to hydrodeboration of
leads to the formation of C6F5H (byproduct) rather than the for- unrecognized arylboron compounds.
mation of K[4-R2NC6F4BF3] due very slow aminodefluorina-
tion with NaNR2 [32].
Reactions with BuLi
In general, reactions of 1-K with BuLi proceed as reactions
Being interested in a wide series of polyfluoroaryltrifluorobo- with MeLi although the precipitation was not observed. The
rates, we investigated possible reaction routes from reaction of BuLi (2 equiv) with 1-K in DME–hexanes at 22 °C
M[C6F5BF3] (M = K, Li and Bu4N) to alkyl-, alkynyl- and aryl- for 2 h and the subsequent treatment of the reaction mixture
tetrafluorophenyltrifluoroborates using the nucleophilic substi- with aqueous KF gave potassium 4-butyltetrafluorophenyltri-
704

Beilstein J. Org. Chem. 2017, 13, 703–713.
Table 1: Reaction of K[C6F5BF3] (1-K) with methyllithium (22 °C, 3 h).
entry
1-K, mg (mmol)
DME, mL MeLi, mL (mmol)
conversion of 1-K, %a
selectivity, %a
2-K
3-K
1
2
3
4
5
6
97 (0.35)
3
3
4
3
3
2
1.5 (0.54)
1.7 (0.61)
2.7 (0.97)
10 (3.6)
51
59
85
100
83
92
83
79
73
55
15
39
11
8
115 (0.41)b
108 (0.39)
276 (1.0)
9
5
113 (0.41)c
170 (0.62)d
2.7 (0.97)
2 (1.28)
—
4
afrom 19F NMR data; bduration 6 h; cat 43–47 °C. Reaction mixture contained C6F5H (0.03 mmol, selectivity 9%) and 2,3,5,6-tetrafluorotoluene (4)
(0.05 mmol, selectivity 15%) and minor unknown components; dreaction mixture was refluxed for 5 h (53–55 °C, bath); the filtrate contained unknown
minor products besides the borates 1-K, 2-K, and 3-K.
Scheme 2: Interaction of K[C6F5BF3] (1-K) with methyllithium (byproducts of hydrodeboration are not depicted).
fluoroborate (6-K) and potassium 2-butyltetrafluorophenyltri- (Scheme 3). An analytically pure sample of 6-K was isolated by
fluoroborate (7-K) (molar ratio 1:0.18) (Table 2, entry 1). In the crystallization of a mixture of 6-K and 7-N from MeCN.
presence of a larger excess of BuLi the quantity of 7-K reduced
to 1:0.10, presumably because of further substitution (Table 2, Reactions with PhLi
entry 2). Heating the reaction mixture at 55–60 °C for 1 h leads The addition of PhLi in ether to a solution of 1-K in DME leads
to substitution of two fluorine atoms with the formation of to the formation of a precipitate similar to that in the reaction
potassium 2,5-dibutyltrifluorophenyltrifluoroborate (8) and with MeLi. Contrary to the nucleophilic alkylation, the use of
potassium 2,4-dibutyltrifluorophenyltrifluoroborate (9) (minor) equimolar amounts of phenyllithium leads to complete
besides 6-K and 7-K (major) (Table 2, entry 3). Using consumption of 1-K and the formation of potassium 4-phenylte-
Li[C6F5BF3] (1-Li) or [Bu4N][C6F5BF3] (1-N) gives the corre- trafluorophenyltrifluoroborate (10-K), potassium 2-phenyltetra-
sponding salts 6-Li, 7-Li and 6-N, 7-N (Table 2, entries 4–6) fluorophenyltrifluoroborate (11-K) and admixtures of potas-
Table 2: Reaction of M[C6F5BF3] (1-M) with butyllithium (22 °C, 2 h).
entry
M
1-M, mg (mmol)
DME, mL
BuLi, mL (mmol)
conversion of 1-M, %a
selectivity, %a
6-M
7-M
1
2
3
4
5
6
K
94 (0.34)
4
0.3 (0.72)
1.2 (2.8)
0.5 (1.2)
1.3 (3.1)
0.4 (0.96)
1.0 (2.5)
100
100
100
97
65
65
71
68
52
74
12
7
K
279 (1.0)
10
3
K
162 (0.59)b
418 (1.50)
200 (0.41)
429 (0.90)
5
Li
6
10
35
25
Bu4N
Bu4N
3
56
6c
80
afrom 19F NMR data; bat 55–60 °C (bath) for 1 h; the reaction mixture contained K[2,5-Bu2C6F3BF3] (8) (0.02 mmol, selectivity 3%) and
K[2,4-Bu2C6F3BF3] (9) (0.03 mmol, selectivity 5%); cin diglyme.
705

Beilstein J. Org. Chem. 2017, 13, 703–713.
Scheme 3: Interaction of M[C6F5BF3] (1-M) with butyllithium (byproducts of hydrodeboration are not depicted).
sium 2,5-diphenyltrifluorophenyltrifluoroborate (12-K) and (Table 3, entry 6). Additionally, 2,3,5,6-tetrafluorobiphenyl (14)
potassium 2,4-diphenyltrifluorophenyltrifluoroborate (13-K) and 2,3,4,5-tetrafluorobiphenyl (15) were found.
(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 Reactions with PhC≡CLi
2 h gave a mixture of starting borate, and small amounts of Attempts to involve 1-K in the reaction with PhC≡CLi failed.
10-K and 11-K (Table 3, entry 2). Prolongation of the reaction Stirring the reagents in DME–ether solution at 22 °C for 17 h
time up to 6 h increases yields of 10-K and 11-K but 1-K leads to recovery of borate 1-K. The same result was obtained
remains a predominant component (Table 3, entry 3). When at 40 °C (2 h) and under reflux (58 °C, bath) for 5 h. It should
1-K reacts with a three-fold excess of PhLi, the yields of be noted that in all cases 1-K was recovered unchanged, e.g., no
monoarylated borates 10-K and 11-K become equal to that of side reactions occurred.
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 In addition to identifying the reaction products by NMR spec-
are the main products while compounds 10-K and 11-K were troscopy, we confirmed their constitution by using the
present in trace amounts (Table 3, entry 5, Scheme 4). Some hydrodeboration reaction. This method consists in replacement
unknown by-products were also formed.
of the BF3 group in polyfluoroaryltrifluoroborates by hydrogen
in alcohol at elevated temperature and obtaining the correspond-
When 1-K reacts with an excess of PhLi (1.6 equiv) at ing polyfluoroarenes in high yields. The latter are more simple
37–40 °C for 1 h, the supernatant after treatment with aqueous substances and available for analysis by NMR spectroscopy,
KF contains 10-K and 11-K besides traces of 1-K and 13-K GC–MS and HRMS methods [33].
Table 3: Reaction of K[C6F5BF3] (1-K) with phenyllithium (22 °C, 2 h).
entry
1-K, mg (mmol) DME, mL
PhLi, mmol
conversion of 1-K, %a
selectivity, %a
10-K
11-K
12-K
13-K
1
94 (0.34)
131 (0.48)
137 (0.50)
124 (0.45)
95 (0.34)
132 (0.48)
3
3
5
5
3
5
0.36
0.39
0.42
1.40
2.10
0.77
100
33
21
19
42
27
6
38
25
38
20
3
15
2
3b
4
52
100
100
96
4
6
40
53
4
5
6c
35
33
afrom 19F NMR data; b6 h; cat 37–40 °C for 1 h; reaction mixture contained 2,3,5,6-tetrafluorobiphenyl (14, 0.01 mmol, selectivity 2%) and 2,3,4,5-
tetrafluorobiphenyl (15, 0.02 mmol, selectivity 4%); borates 1, 10, 11 and 13 are lithium salts.
706

Beilstein J. Org. Chem. 2017, 13, 703–713.
Scheme 4: Interaction of K[C6F5BF3] (1-K) with phenyllithium (byproducts of hydrodeboration are not depicted).
Heating a mixture of 6-K, 7-K, 8-K and 9-K in MeOH leads to Discussion
conversion of these salts to 16, 17, 18 and 19, respectively. The Above we mentioned that an addition of MeLi or PhLi in ether
molar ratio of the produced polyfluoroarenes is the same as the to a solution of 1-K in DME caused immediate precipitation.
ratio of their organoboron precursors (Scheme 5).
The combination of 1-K in DME with BuLi in hexanes or
PhC≡CLi in ether does not lead to the formation of a solid
The 19F NMR spectrum of 17 was described [34] and the spec- phase. Because etherial solutions of MeLi and PhLi were pre-
trum of 16 is closely related to the spectrum of known com- pared from lithium and MeI or PhBr, they contain the corre-
pound 4 [33]. The structures of 18 and 19 are consistent with sponding lithium halides. It follows that the precipitate consists
19F NMR, GC–MS and HRMS data.
of KI and KBr, respectively, and the actual boron-containing
reactant is lithium pentafluorophenyltrifluoroborate (1-Li). In-
For characterization of the products derived from 1-K and PhLi dependently, Li[C6F5BF3] was prepared by metathesis of 1-K
we performed the hydrodeboration of a mixture of 1-K, 10-K with LiHal (Hal = Cl, Br, I) in an approapriate solvent
and 11-K by stirring it in 2-methoxyethanol under reflux. After (Scheme 8). After determination of the salt concentration by
evaporation of the alcohol and C6F5H, the known 2,3,5,6-tetra- 19F NMR, 1-Li was used in DME without isolation. When the
fluorobiphenyl (14) [35,36] and 2,3,4,5-tetrafluorobiphenyl (15) metathesis was performed in MeCN, the lithium salt was isolat-
[35,36] were obtained (Scheme 6).
ed from MeCN as solid solvate Li[C6F5BF3]·2MeCN. Dissolu-
tion of the solvate in DME leads to liberation of free MeCN
Then a mixture of borates 10-K, 11-K, 12-K, and 13-K was (1H NMR). [Bu4N][C6F5BF3] (1-N) was prepared in similar
converted to biphenyls 14, 15, and terphenyls 20, 21, respec- way from 1-K and [Bu4N]Br in MeCN and after removal of the
tively, and characterized by 19F NMR spectroscopy, GC–MS solvent from the supernatant it was dissolved in DME or
and HRMS (Scheme 7).
diglyme.
Scheme 5: Hydrodeboration of 6-K, 7-K, 8-K and 9-K in MeOH.
707

Beilstein J. Org. Chem. 2017, 13, 703–713.
Scheme 6: Hydrodeboration of 1-K, 10-K and 11-K in methyl cellosolve.
Scheme 7: Hydrodeboration of 10-K, 11-K, 12-K and 13-K in MeOH.
In the course of these experiments we paid attention on distinc- 1.51 ppm, respectively. The opposite is the case in the
tions in the NMR spectra of M[C6F5BF3] (M = Li, K, Bu4N) 19F NMR spectra. The signal of BF3 group shifts from −137.2
(Table 4).
(1-Li) to −134.2 (1-K) and −132.4 (1-N) ppm in DME solution
or to −134.1 ppm (1-N) in CH2Cl2. The positions of the fluo-
The replacement of Li+ by K+ and Bu4N+ is accompanied with rine atoms of the C6F5 moiety are weakly sensitive to the nature
remarkable changes in the NMR spectra. In the 11B NMR spec- of the counteranion although the fluorine atoms F2,6 of 1-N in
trum the signal of BF3 group shifts from 2.31 (M = Li) to 2.24 CH2Cl2 are somewhat shielded with respect to those in diglyme
(M = K) and 1.89 (M = Bu4N) ppm (in DME). In solutions of and DME. It is reasonable to assume that these spectral phe-
1-N in diglyme and CH2Cl2 this signal locates at 1.68 and nomena reflect the different solvation of M[C6F5BF3]. Detailed
Scheme 8: Preparation of 1-Li and 1-N.
708

Beilstein J. Org. Chem. 2017, 13, 703–713.
Table 4: The 11B and 19F NMR spectra of M[C6F5BF3]a.
borate
solvent
δ(B)
δ(F)
BF3
F2,6
F4
F3,5
Li[C6F5BF3]
DME
2.31
1.73
2.24
1.81
1.89
1.68
−137.2
−135.3
−134.2
−133.4
−132.4
−132.4
−134.1
−134.6
−134.4
−135.2
−133.1
−133.1
−161.3
−159.9
−161.3
−160.7
−162.6
−162.0
−165.9
−164.9
−165.6
−165.3
−166.3
−165.8
Li[C6F5BF3]
CD3CN
DME
K[C6F5BF3]
K[C6F5BF3] [28]
[Bu4N][C6F5BF3]
[Bu4N][C6F5BF3]
CD3CN
DME
diglyme
ain all cases 1J(B, F) = 43–44 Hz and 3J(F4, F3,5) ca. 20 Hz.
investigations in this field are out of the scope of the current ligand and that ratio decreases to 1:0.35 (Table 2, entries 5
research but some qualitative considerations may be outlined. In and 6).
solution of 1-Li in DME the lithium cation is strongly coordi-
nated with one or multiple fluorine atoms bonded to boron When R = Ph, the ratio [4-PhC6F4BF3]−/[2-PhC6F4BF3]−
(“hard”–“hard” interaction) and with solvent molecules to form derived from 1-Li and 0.8 equiv of PhLi increases up to
contact ion pair [37]. The opposite situation is in 1-N where the 1:(0.9–1.3) (Table 3, entries 2, 3 and 6). Other data from
bulky tetrabutylammonium cation (“soft”) interacts with those Table 3 are not reliable for comparison because the initial ratio
fluorine atom(s) weaker than Li+ either in DME and diglyme is remarkably corrupted by the further reactions. We believe
and this salt forms solvent-separated ion pairs. Potassium penta- that the enrichment of the reaction mixture in [2-PhC6F4BF3]−
fluorophenyltrifluoroborate is the intermediate position. The occurs because of an additional stabilization of transition state
11B and 19F NMR chemical shifts of BF3 group in 1-K in DME A (Scheme 9) due to the π-stacking interactions between C6H5
are closely related to the shifts of 1-Li in the same solvents and and C6F5 moieties (Scheme 10), which is excluded in cases of
reflect the formation of contact ion pairs. In acetonitrile the salts nucleophilic alkylation.
1-Li and 1-N form solvent-separated ion pairs (11B and
19F NMR). These observations eludicate the effect of counter- While reactions of K[C6F5BF3] with C-nucleophiles give the
actions on the isomer compositions of M[RC6F4BF3]. In DME significant amount of K[2-NuC6F4BF3] the related isomers are
both salts, 1-Li and 1-K, exist as the contact ion pairs and thus not formed under the action of O-nucleophiles, RONa, and
the molar ratios of [4-BuC6F4BF3]−/[2-BuC6F4BF3]− should be N-nucleophiles, AzNa (Az = azol-1-yl). Only a few borates
similar. Indeed, the ratio of these products derived from 1-Li K[3,4-Az2C6F3BF3] (Az = indol-1-yl, benzimidazol-1-yl) were
and 1-K are 1:0.15 and 1:0.18, respectively. Nucleophilic detected in the last reaction [32]. The substitution of a fluorine
methylation of 1-Li also results in a related value 1:(0.10–0.13) atom in 1-K by the RO group (in the reaction with 1 equiv of
(Table 1, Table 2), i.e., the isomer ratio remains constant within RONa) gives only K[4-ROC6F4BF3] [31]. However, the reac-
the experimental error. Salt 1-N exists in DME as solvent-sepa- tion with 3 equiv of MeONa under the same conditions gives
rated ion pair. Because of this the fluorine atom of BF3 is more potassium 3,4-dimethoxytrifluorophenyltrifluoroborate (22) and
accessible to coordinate RLi and the ratio [4-BuC6F4BF3]− to potassium 2,4-dimethoxytrifluorophenyltrifluoroborate (23)
[2-BuC6F4BF3]− becomes 1:0.66. Diglyme is a more bulky besides K[4-MeOC6F4BF3] and 2,3,5,6-tetrafluorophenol. The
Scheme 9: Formation of 2-R-tetrafluorophenyltrifluoroborates.
709

Beilstein J. Org. Chem. 2017, 13, 703–713.
electron-withdrawing substituent CH3 (σI ≈ 0.0 [41]) remains
inert towards PhC≡CLi even in DME–ether [39].
When pentafluorophenyltrifluoroborates react with MeLi (Ta-
ble 1, entries 5 and 6) or PhLi (Table 3, entry 6) in DME–ether
at elevated temperature, partial hydrodeboration of
M[RC6F4BF3] as well as M[R2C6F3BF3] occurs in addition to
nucleophilic substitution. This process was not observed for
Scheme 10: Interaction between C6F5BF3− and PhLi.
latter are formed because of some moisture in MeOH [31] BuLi in hexanes and PhC≡CLi in ether at 40–60 °C. We
(Scheme 11).
assumed that this side reaction proceeds because of the interac-
tion of M[RC6F5BF3] with LiHal, which is present in solutions
In our opinion, the reason of the negligible content of isomer of MeLi and PhLi in ether and absent in solutions of BuLi and
[2-NuC6F4BF3]− is the lesser affinity to fluoride of Na+ and K+ PhC≡CLi. Indeed, heating 1-K with LiHal (Hal = I, Br, or Cl)
compared with Li+ (considerations on the relative fluoride in DME at 55–70 °C leads to the formation of C6F5H.
affinities are grounded on the crystal lattice energy of LiF [Bu4N][C6F5BF3] reacts with LiI in diglyme in a similar way.
(1027 kJ·mol−1), NaF (914 kJ·mol−1) and KF (812 kJ·mol−1) Because the cations K+ or Bu4N+ are replaced with Li+ in all
[38]) and the ionic nature of RO–M and RR'N–M (M = K, Na) cases, the reactions proceed via the lithium salt. Actually, the
bonds in the examined nucleophiles. Even in spite of the salt Li[C6F5BF3] prepared from 1-K and an excess of LiI at
possible coordination of K+ or Na+ with the BF3 group, free 22 °C in quantitative yield converted to C6F5H in high yield
anions RO− or RR'N− attack the carbon atom C-4 rather than when being heated in DME at 55–70 °C (Scheme 12). A simi-
C-2 and C-6.
lar reaction of 1-K occurs in MeOH in the presence of LiCl
[33].
The tolerance of 1-K towards PhC≡CLi is a consequence of the
low nucleophilicity of PhC≡CLi. For instance, C6F6 and Presumably, one role of lithium halides is the fluoride abstrac-
C6F5C6F5 do not react with PhC≡CLi in ether, although the ad- tion from lithium aryltrifluoroborate (or significant polarization
dition of a coordinating solvent (DME, diglyme [39], THF [40]) of the B–F bond) and the subsequent hydrodeboration of aryl-
accelerates nucleophilic substitution. C6F5CH3 bearing the non- difluoroborane by residual moisture in the solvent (Scheme 13).
Scheme 11: Interaction of 1-K with MeONa.
Scheme 12: Interaction of M[RC6F5BF3] with lithium halides.
710

Beilstein J. Org. Chem. 2017, 13, 703–713.
Scheme 13: Assumed role of lithium halides.
This assumption is evidenced by the fact that lithium salts are K[C6F5BF3] does not react with PhC≡CLi in DME–ether under
used as catalysts for the reverse transformation of organotri- reflux because the low reactivity of C-nucleophile.
fluoroborates in the corresponding organoboronic acids.
2. Because solutions of MeLi and PhLi contain LiBr or LiI, the
In the absence of LiHal, borate 1-Li does not change in DME salts M[C6F5BF3] (M = K, Bu4N) undergo metathesis with the
(22 °C, 1 week; 60–68 °C, 5 h), and neither does 1-N in formation of Li[C6F5BF3]. The latter is the actual reagent in the
diglyme (22 °C, 1 year; 60–68 °C, 5 h). This observation reactions of nucleophilic substitution. BuLi in hexanes does not
contrasts with the reactivity of the close analogue, contain LiHal and thus it reacts with K[C6F5BF3].
Li[C6F5B(OMe)3], which undergoes hydrodeboration in metha-
nol, acetone or acetonitrile. Li[C6F5B(OMe)3] converts to 3. According to the 11B and 19F NMR data, salts Li[C6F5BF3]
Li[(C6F5)2B(OMe)2] and Li[B(OMe)4] at 22 °C in DME. Also and K[C6F5BF3] exists as contact ion pairs in DME and sol-
disproportionation of M[C6F5B(OMe)3] (M = Li, K) proceeds vent-separated ion pairs in CH3CN. [Bu4N][C6F5BF3] forms
in weakly coordinated CH2Cl2 in the presence of [Bu4N]Br or solvent-separated ion pairs in DME or diglyme. The sort of
KF while in the absence of other salts the lithium salt is rela- solvation affects the ratio M[4-RC6F4BF3]/M[2-RC6F4BF3]: In
tively stable. This phenomenon was explained by the formation case of the contact ion pairs the contribution of the ortho alkyl-
of a dinuclear methoxy-bridged borate intermediate ation is minimal (M = K, Li). During nucleophilic phenylation
[C6F5B(OMe)2–(μ-OMe)–B(OMe)2C6F5]− (B) followed the the π–stacking interaction between C6H5 and C6F5 moieties can
migration of both the aryl and the methoxy groups. If Li+ and be responsible for increased yield of M[2-PhC6F4BF3].
[C6F5B(OMe)3]− form a contact ion pair (solution of
Li[C6F5B(OMe)3] in CH2Cl2), such migration of −OMe and its 4. The formation of M[2-RC6F4BF3] proceeds through the coor-
subsequent elimination is hindered [42]. In the case of penta- dination of RLi (polarized C–Li bond) to a fluorine atom of the
fluorophenyltrifluoroborates the similar conversion does not BF3 moiety and subsequent elimination of LiF. In contrary, the
occur even with Li[C6F5BF3] in DME (contact ion pairs) due to cation–anion bonds in O-nucleophiles and in N-nucleophiles are
the higher Lewis acidity of C6F5BF2 relative to C6F5B(OMe)2, ionic (M = K, Na) and the fluoride affinities of K+ and Na+ are
which prevents the formation of fluoro-bridged intermediates smaller than that of Li+. These factors determine the reaction
such as B.
route with K[C6F5BF3] by a simple SN2 mechanism.
Conclusion
Supporting Information
1. Nucleophilic substitution of fluorine atoms in M[C6F5BF3]
(M = K, Li, Bu4N) with MeLi or BuLi at 22 °C and subsequent
treatment with aqueous KF leads preferentially to
K[4-RC6F4BF3] while K[2-RC6F4BF3] is a minor isomer
(R = Me, Bu). Under the same conditions, the reaction with
PhLi gives approximately equimolar amounts of
K[4-PhC6F4BF3] and K[2-PhC6F4BF3] and remarkable
amounts of K[2,5-Ph2C6F3BF3] and K[2,4-Ph2C6F3BF3]. The
substitution of two fluorine atoms by the butyl group at
55–60 °C gives the related isomers while a complex mixture
forms from K[C6F5BF3] and MeLi at the same temperature.
Supporting Information File 1
Full experimental details and compounds characterization
data.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-13-69-S1.pdf]
Acknowledgements
The authors would like to express gratitude for financial support
from the Russian Fund of Basic Research through Grant No.
711

Beilstein J. Org. Chem. 2017, 13, 703–713.
23.Bardin, V. V.; Shabalin, A. Y.; Adonin, N. Y. Beilstein J. Org. Chem.
2015, 11, 608–616. doi:10.3762/bjoc.11.68
16-29-10762 ofi_m. The NMR spectra and GC-MS data were
obtained in the Collective service center of SB RAS (N.N.
Vorozhtsov Novosibirsk Institute of Organic Chemistry SB
RAS).
24.Shabalin, A. Y.; Adonin, N. Y.; Bardin, V. V.; Parmon, V. N.
Tetrahedron 2014, 70, 3720–3725. doi:10.1016/j.tet.2014.04.019
25.Frohn, H.-J.; Adonin, N. Y.; Bardin, V. V.; Starichenko, V. F.
J. Fluorine Chem. 2002, 117, 115–120.
doi:10.1016/S0022-1139(02)00157-4
References
26.Frohn, H.-J.; Adonin, N. Y.; Bardin, V. V.; Starichenko, V. F.
J. Fluorine Chem. 2003, 122, 195–199.
1. Stefani, H. A.; Cella, R.; Vieira, A. S. Tetrahedron 2007, 63,
3623–3658. doi:10.1016/j.tet.2007.01.061
doi:10.1016/S0022-1139(03)00088-5
2. Darses, S.; Genet, J.-P. Chem. Rev. 2008, 108, 288–325.
doi:10.1021/cr0509758
27.Frohn, H.-J.; Adonin, N. Y.; Bardin, V. V.; Starichenko, V. F.
Tetrahedron Lett. 2002, 43, 8111–8114.
3. Molander, G. A.; Canturk, B. Angew. Chem., Int. Ed. 2009, 48,
9240–9261. doi:10.1002/anie.200904306
doi:10.1016/S0040-4039(02)01922-6
28.Frohn, H.-J.; Franke, H.; Fritzen, P.; Bardin, V. V. J. Organomet. Chem.
2000, 598, 127–135. doi:10.1016/S0022-328X(99)00690-7
29.Adonin, N. Y.; Bardin, V. V.; Frohn, H.-J.
4. Molander, G. A.; Sandrock, D. L. Curr. Opin. Drug Discovery Dev.
2009, 12, 811–823.
5. Perrin, D. M. Acc. Chem. Res. 2016, 49, 1333–1343.
doi:10.1021/acs.accounts.5b00398
Collect. Czech. Chem. Commun. 2008, 73, 1681–1692.
doi:10.1135/cccc20081681
6. Savitha, B.; Sajith, A. M.; Joy, M. N.; Khader, K. K. A.;
Muralidharan, A.; Padusha, M. S. A.; Bodke, Y. D. Aust. J. Chem.
2016, 69, 618–630. doi:10.1071/ch15420
30.Adonin, N. Y.; Prikhod’ko, S. A.; Bardin, V. V.; Parmon, V. N.
Mendeleev Commun. 2009, 19, 260–262.
doi:10.1016/j.mencom.2009.09.009
7. Fisher, K. M.; Bolshan, Y. J. Org. Chem. 2015, 80, 12676–12685.
doi:10.1021/acs.joc.5b02273
31.Shabalin, A. Y.; Adonin, N. Y.; Bardin, V. V.; Prikhod'ko, S. A.;
Timofeeva, M. N.; Bykova, M. V.; Parmon, V. N. J. Fluorine Chem.
2013, 149, 82–87. doi:10.1016/j.jfluchem.2013.01.020
32.Shabalin, A. Y.; Adonin, N. Y.; Bardin, V. V.; Taran, O. P.;
Ayusheev, A. B.; Parmon, V. N. J. Fluorine Chem. 2013, 156, 290–297.
doi:10.1016/j.jfluchem.2013.07.011
8. Brady, P. B.; Carreira, E. M. Org. Lett. 2015, 17, 3350–3353.
doi:10.1021/acs.orglett.5b01607
9. Liu, Z.; Chao, D.; Li, Y.; Ting, R.; Oh, J.; Perrin, D. M. Chem. – Eur. J.
2015, 21, 3924–3928. doi:10.1002/chem.201405829
10.Erős, G.; Kushida, Y.; Bode, J. W. Angew. Chem., Int. Ed. 2014, 53,
7604–7607. doi:10.1002/anie.201403931
33.Adonin, N. Y.; Shabalin, A. Y.; Bardin, V. V. J. Fluorine Chem. 2014,
168, 111–120. doi:10.1016/j.jfluchem.2014.09.016
34.Bogachev, A. A.; Kobrina, L. S. Russ. J. Org. Chem. 1997, 33,
681–683.
11.Berionni, G.; Morozova, V.; Heininger, M.; Mayer, P.; Knochel, P.;
Mayr, H. J. Am. Chem. Soc. 2013, 135, 6317–6324.
doi:10.1021/ja4017655
35.Bolton, R.; Sandall, J. P. B.; Williams, G. H. J. Fluorine Chem. 1974, 4,
355–361. doi:10.1016/S0022-1139(00)85284-7
36.Wei, Y.; Kan, J.; Wang, M.; Su, W.; Hong, M. Org. Lett. 2009, 11,
3346–3349. doi:10.1021/ol901200g
12.Lee, J.-H.; Kim, H.; Kim, T.; Song, J. H.; Kim, W.-S.; Ham, J.
Bull. Korean Chem. Soc. 2013, 34, 42–48.
doi:10.5012/bkcs.2013.34.1.42
13.Frohn, H.-J.; Giesen, M.; Welting, D.; Bardin, V. V. J. Fluorine Chem.
2010, 131, 922–932. doi:10.1016/j.jfluchem.2010.06.006
14.Frohn, H.-J.; Wenda, A.; Flörke, U. Z. Anorg. Allg. Chem. 2008, 634,
764–770. doi:10.1002/zaac.200700499
37.Szwarc, M. Ions and Ion Pairs in Organic Reactions; John Wiley &
Sons: New York, NY, USA, 1974.
38.Stokes, R. H. J. Am. Chem. Soc. 1964, 86, 982–986.
doi:10.1021/ja01060a003
15.Frohn, H.-J.; Hirschberg, M. E.; Wenda, A.; Bardin, V. V.
J. Fluorine Chem. 2008, 129, 459–473.
39.Coe, P. L.; Tatlow, J. C.; Terrell, R. C. J. Chem. Soc. C 1967,
2626–2628. doi:10.1039/J39670002626
doi:10.1016/j.jfluchem.2008.04.001
40.Wiles, M. R.; Massey, A. G. J. Organomet. Chem. 1973, 47, 423–432.
doi:10.1016/S0022-328X(00)81754-4
16.Frohn, H.-J.; Bardin, V. V. Z. Anorg. Allg. Chem. 2008, 634, 82–86.
doi:10.1002/zaac.200700319
41.Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165–195.
doi:10.1021/cr00002a004
17.Frohn, H.-J.; Bardin, V. V. Organoxenonium Salts: Synthesis by
"Xenodeborylation", Reactivities, and NMR Spectroscopic Properties.
In Recent Developments in Carbocation and Onium Ion Chemistry;
Laali, K. K., Ed.; ACS Symposium Series, Vol. 965; American Chemical
Society: Washington, DC, 2007; pp 428–457.
42.Adonin, N. Y.; Bardin, V. V.; Flörke, U.; Frohn, H.-J.
Z. Anorg. Allg. Chem. 2005, 631, 2638–2646.
doi:10.1002/zaac.200500083
doi:10.1021/bk-2007-0965.ch020
18.Koppe, K.; Frohn, H.-J.; Mercier, H. P. A.; Schrobilgen, G. J.
Inorg. Chem. 2008, 47, 3205–3217. doi:10.1021/ic702259c
19.Koppe, K.; Bilir, V.; Frohn, H.-J.; Mercier, H. P. A.; Schrobilgen, G. J.
Inorg. Chem. 2007, 46, 9425–9437. doi:10.1021/ic7010138
20.Frohn, H.-J.; Bardin, V. V. Mendeleev Commun. 2007, 17, 137–138.
doi:10.1016/j.mencom.2007.05.001
21.Frohn, H.-J.; Bardin, V. V. Eur. J. Inorg. Chem. 2006, 3948–3953.
doi:10.1002/ejic.200600366
22.Adonin, N. Y.; Babushkin, D. E.; Parmon, V. N.; Bardin, V. V.;
Kostin, G. A.; Mashukov, V. I.; Frohn, H.-J. Tetrahedron 2008, 64,
5920–5924. doi:10.1016/j.tet.2008.04.043
712

Beilstein J. Org. Chem. 2017, 13, 703–713.
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.13.69
713